User:Dr3939/沙盒

User:Dr3939/沙盒/Test

使用者:Dr3939/VideoWiki/痛風 草稿:VideoWiki:Gout

A	B	C
1	2	3

歷史

個人維基史

User:Dr3939/翻譯史 [3] 摘要 - 色素沉著絨毛結節性滑膜炎 費爾蒂症候群 單株抗體治療 自體免疫

User:Dr3939/VideoWiki/痛風 User:Dr3939/沙盒/Test

1. 來曲唑, 醋酸甲羥孕酮 - 2024/11/19, 摘要
2. 依托孕烯 - 2024/11/18, 摘要
3. 左乙拉西坦, 替扎尼定, 鐵劑, 亞葉酸, 抗Rh因子免疫球蛋白 - 2024/11/15, 摘要
4. 口周皮膚炎, 顳顎關節功能障礙 - 2024/11/14, 摘要
5. 梨狀肌症候群, 前十字韌帶受傷 - 2024/11/13, 摘要
6. 髖關節發育不良, 醋甲唑胺, 胃輕癱, 乙型阻斷劑中毒 - 2024/11/12, 摘要
7. 缺血性壞死, 硬化性苔癬, 托吡酯, 氟氫可體松, 肛門疼痛, 尿素乳膏 - 2024/11/10, 摘要
8. 姿勢性心博過速症候群, 外陰搔癢 - 2024/11/09, 摘要
9. 氯沙坦, 淋巴水腫, 感覺異常, 子宮破裂 - 2024/11/08, 摘要
10. 巴瑞替尼, 托法替尼, 依奇珠單抗 - 2024/11/06, 摘要
11. 古塞奇尤單抗, 利生奇珠單抗, 羅莫珠單抗, 阿伏利尤單抗 - 2024/11/05, 摘要
12. 司庫奇尤單抗, 伊班膦酸, 來氟米特 - 2024/11/04, 摘要
13. 烏帕替尼, 阿巴西普, 類A酸, 冷凍沉澱品, 舒林酸 - 2024/11/03, 摘要
14. Template:腫瘤伴隨症候群 - 2024/11/02, 範本, 全
15. 抗NMDA受體腦炎, 絨毛羊膜炎, 妊娠多形疹 - 2024/11/02, 摘要
16. 腎上腺功能不全, 複雜性局部疼痛症候群, 暫時性滑膜炎 - 2024/11/01, 摘要
17. 藥物疹合併嗜伊紅血症及全身症狀, 脂肪乳, 鷹嘴突滑囊炎, 血小板減少症, 髕骨肌腱炎, 結節性紅斑, 壞疽性膿皮症, 心包積液 - 2024/10/31, 摘要
18. 髕前滑囊炎, 靜脈炎, 氫羥腎上腺皮質素, 硫酸锌 (藥品), 那曲酮, 磺达肝癸钠 - 2024/10/30, 摘要
19. 風濕性多肌痛症 - 2024/10/29, 摘要
20. 肋軟骨炎 - 2024/10/28, 摘要
21. 掌腱膜攣縮症 - 2024/10/27, 摘要
22. 藥物不良反應 - 2024/01/14, 全
23. NUDT15 - 2023/12/24, 全
24. 前景問題格式, 證據等級, Category:實證應用‎, Template:實證應用, Template:實證醫學應用 - 2022/4/24-5/08, WikiMed X TEBMA, 全, 編修+審查
25. 二水合焦磷酸鈣晶體沉積病 - 2021/12/06-12/08, 全
26. Template:骨軟骨病 - 2021/11/28, 範本, 全-更新
27. 羥氯喹 - 2020/04/12, 醫週譯小時, 摘要
28. 磺胺嘧啶, 結節病, Template:Sarcoidosis - 2020/04/04, 醫週譯小時, 全-摘要-範本
29. 自體免疫, 軟組織疾病, 黃房子 (梵高) - 2020/01/27, 長條目, 摘要／全／擴充
30. 風濕, 單株抗體治療, 單克隆抗體治療 - 2020/01/26, 長條目, 全/摘要.
31. Template:兒童關節炎 - 2020/01/23, 範本, 全；鋅缺乏 - 2020/01/23, 審查
32. 幼年特發性關節炎 - 2020/01/15, 長條目, 全
33. Template:滑液檢查‎ - 2020/01/12, 範本, 全
34. 敗血性關節炎‎ - 2020/01/08, 長條目, 全
35. Template:骨軟骨病 - 2020/1/6, 範本, 全
36. v 反覆性風濕症 - 2020/1/3, 小作品級, 全
37. 骨贅, 骨質增生 - 2020/1/1, 小作品級, 全
38. 反應性關節炎, 萊特氏症候群 - 2019/12/22, 長條目, 全
39. v 成人史迪爾氏病, 成人史迪爾氏症候群 - 2019/12/21, 長條目, 全
40. 關節痛 - 2019/12/19, 長條目, 全
41. 骨頭侵蝕, 骨侵蝕 - 2019/12/18, 長條目, 全
42. 寡關節炎 - 2019/12/10, 長條目, 全
43. 愛迪生氏病, 恶性贫血 - 2019/12/04, 醫週譯小時
44. 著骨點炎, 接骨點炎, 附著部炎, 著骨點病變, 接骨點病變, 附著部病變 - 2019/11/18, 長條目, 全
45. 脊椎炎, 脊椎病變, 薦腸關節炎, 椎間盤炎, 脊椎椎間盤炎, 博特氏病 - 2019/11/17, 長條目, 全
46. 關節僵硬, 關節積血, 絨毛結節性滑膜炎, 色素沉著絨毛結節性滑膜炎 (摘要), Category:風濕病學, v 風濕病學 - 2019/11/16, 長條目, 全
47. v 希伯登氏結節, 布夏氏結節 - 2019/11/15, 小作品級, 全
48. 單關節炎, 多關節炎, 費爾蒂症候群, 結晶性關節病變, 軟骨鈣質沈積病 - 2019/11/13, 小作品級, 全
49. SpA, 脊椎關節炎, 血清陰性脊椎關節病變, SPA (消歧義), v 乾癬性關節炎 - 2019/11/12, 轉址 - 擴充 - 長條目, 全
50. 關節病變, 脊椎關節病變 - 2019/11/11, 小作品級, 全
51. Template:過敏及自體免疫疾病, Template:全身性結締組織疾病, Template:全身性血管炎, Template:過敏狀況 - 2019/11/10, 範本, 全
52. Template:自體抗原 - 2019/11/09, 範本, 全
53. Template:關節病變和相關疾病, Template:脊椎疾病 - 2019/11/08, 範本, 全
54. v 反覆流產 - 2019/10/29-11/03 , 長條目, 全
55. v 流產 - 2019/10/19-10/29, 長條目, 全, 補充 及 更新;
56. 失智症 - 2019/10/13, 長條目, 部分, 醫週譯小時;
57. v 類風濕因子, Template:自體抗體 - 2019/10/08-10/10 長條目/範本, 全
58. v 抗甲狀腺自體抗體 - 2019/10/07-10/09, 長條目, 部分 及 整合
59. 結節性甲狀腺腫 - 2019/10/08, 消歧義, 全
60. Category:腳部疾病‎, Category:過度使用傷害‎, Category:软组织疾病‎‎, Template:軟組織疾病 2019/09/27, 類別/範本, 全 及 補充
61. v 足底筋膜炎 - 2019/09/10~9/20, 長條目, 部分, 醫週譯小時; 9/21-22 整合
62. v 女性不孕症 - 2019/09/09~10/04, 長條目, 部分
63. v 不孕 - 2019/09/04~9/07, 長條目, 部分
64. 生酮飲食 Draft:生酮飲食 - 2019/08/20~9/03, 長條目, 部分
65. 拉米夫定 - 2019/08/19, 醫週譯小時
66. 肝豆狀核變性, 三環類抗抑鬱藥藥物過量 - 2019/08/16, 醫週譯小時
67. v 實證醫學 - 2019/08/11~8/20, 長條目, 全

---

開始：實證醫學

• Evidence based medicine > 内容翻译 > User:Dr3939/實證醫學 + Draft:實證醫學 > 實證醫學
  • 8/11 8:00 上午動念要翻譯，在 facebook 上找人介紹熟 wikipedia/wikimed 的朋友，三個小時後就加入兩位好友，並加入維基醫學翻譯社群WikiMed
  • 接著就克文件準備動手，8/11 23:00 左右開始使用 內容翻譯功能 翻譯到 User:Dr3939/實證醫學 8/20 23:00 左右，翻完初稿。
  • 8/20 再加兩位好友，再將 User:Dr3939/實證醫學 與用 連結翻譯器 產生的 Draft:實證醫學 校稿合併
  • 8/24 23:00 完工

---

• 首次建立帳號 2005年3月22日 (二) 14:01‎

重疊症候群 抗環瓜氨酸肽抗體 外生骨贅 en:Exostosis en:Template:Osteochondropathy 模板:骨軟骨病 著骨點增生 en:Inflammatory arthritis

全身發作型幼年特發性關節炎

en:Systemic-onset juvenile idiopathic arthritis 全身發作型幼年特發性關節炎 兒童關節炎

自體免疫

自體免疫

自體免疫

免疫耐受性

• 株落忽视理論指出在胸腺中未顯現自身反應性的 T 細胞將成熟並遷移到週邊組織，在週邊組織內，T 細胞無法接近的組織，所以不會遇到合適的抗原。因此，逃脫株落刪除的自身反應性 B 細胞無法找到抗原或特定的輔助性T細胞來活化它們。

• 抑制群體或調節T細胞理論：調節性 T 淋巴細胞（通常為 CD4⁺FoxP3⁺ 細胞）的工作在於預防、下調或限制免疫系統中的自身反應性被激活。

Tolerance can also be differentiated into "central" and "peripheral" tolerance, on whether or not the above-stated checking mechanisms operate in the central lymphoid organs (thymus and bone marrow) or the peripheral lymphoid organs (lymph node, spleen, etc., where self-reactive B-cells may be destroyed). It must be emphasised that these theories are not mutually exclusive, and evidence has been mounting suggesting that all of these mechanisms may actively contribute to vertebrate immunological tolerance.

關於上述檢查機制是在中央淋巴器官（胸腺和骨髓）還是在外周淋巴器官（淋巴結，脾臟等）中起作用，耐受性還可以分為“中心”耐受性和“外周”耐受性。 ，其中自反應性B細胞可能會被破壞）。 必須強調的是，這些理論並不是相互排斥的，並且越來越多的證據表明所有這些機制都可能積極地促進脊椎動物的免疫耐受。

A puzzling feature of the documented loss of tolerance seen in spontaneous human autoimmunity is that it is almost entirely restricted to the autoantibody responses produced by B lymphocytes. Loss of tolerance by T cells has been extremely hard to demonstrate, and where there is evidence for an abnormal T cell response it is usually not to the antigen recognised by autoantibodies. Thus, in rheumatoid arthritis there are autoantibodies to IgG Fc but apparently no corresponding T cell response. In systemic lupus there are autoantibodies to DNA, which cannot evoke a T cell response, and limited evidence for T cell responses implicates nucleoprotein antigens. In Celiac disease there are autoantibodies to tissue transglutaminase but the T cell response is to the foreign protein gliadin. This disparity has led to the idea that human autoimmune disease is in most cases (with probable exceptions including type I diabetes) based on a loss of B cell tolerance which makes use of normal T cell responses to foreign antigens in a variety of aberrant ways.   

自發性人類自體免疫中所見的耐受性喪失的一個令人困惑的特徵是，它幾乎完全限於B淋巴細胞產生的自身抗體反應。很難證明T細胞喪失了耐受性，並且在有證據表明存在異常的T細胞反應的情況下，通常不是針對自身抗體識別的抗原。因此，在類風濕關節炎中，存在針對IgG Fc的自身抗體，但顯然沒有相應的T細胞應答。在系統性狼瘡中，有針對DNA的自身抗體，無法引起T細胞反應，而有關T細胞反應的證據有限，這牽涉到核蛋白抗原。在乳糜瀉中，存在針對組織轉谷氨酰胺酶的自身抗體，但T細胞對外源蛋白麥醇溶蛋白的反應。這種差異導致了這樣一種觀念，即人類自體免疫性疾病在大多數情況下（可能包括I型糖尿病）（基於B細胞耐受力喪失）是基於B細胞耐受性喪失的原因，而B細胞以各種異常方式利用了正常T細胞對外源抗原的反應。

Immunodeficiency and autoimmunity

There are a large number of immunodeficiency syndromes that present clinical and laboratory characteristics of autoimmunity. The decreased ability of the immune system to clear infections in these patients may be responsible for causing autoimmunity through perpetual immune system activation.

One example is common variable immunodeficiency (CVID) where multiple autoimmune diseases are seen, e.g.: inflammatory bowel disease, autoimmune thrombocytopenia and autoimmune thyroid disease.

Familial hemophagocytic lymphohistiocytosis, an autosomal recessive primary immunodeficiency, is another example. Pancytopenia, rashes, swollen lymph nodes and enlargement of the liver and spleen are commonly seen in such individuals. Presence of multiple uncleared viral infections due to lack of perforin are thought to be responsible.

In addition to chronic and/or recurrent infections many autoimmune diseases including arthritis, autoimmune hemolytic anemia, scleroderma and type 1 diabetes mellitus are also seen in X-linked agammaglobulinemia (XLA). Recurrent bacterial and fungal infections and chronic inflammation of the gut and lungs are seen in chronic granulomatous disease (CGD) as well. CGD is a caused by decreased production of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by neutrophils. Hypomorphic RAG mutations are seen in patients with midline granulomatous disease; an autoimmune disorder that is commonly seen in patients with granulomatosis with polyangiitis and NK/T cell lymphomas.

Wiskott–Aldrich syndrome (WAS) patients also present with eczema, autoimmune manifestations, recurrent bacterial infections and lymphoma.

In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) also autoimmunity and infections coexist: organ-specific autoimmune manifestations (e.g. hypoparathyroidism and adrenocortical failure) and chronic mucocutaneous candidiasis.

Finally, IgA deficiency is also sometimes associated with the development of autoimmune and atopic phenomena.

Genetic factors

Certain individuals are genetically susceptible to developing autoimmune diseases. This susceptibility is associated with multiple genes plus other risk factors. Genetically predisposed individuals do not always develop autoimmune diseases.

Three main sets of genes are suspected in many autoimmune diseases. These genes are related to:

• Immunoglobulins
• T-cell receptors
• The major histocompatibility complexes (MHC).

The first two, which are involved in the recognition of antigens, are inherently variable and susceptible to recombination. These variations enable the immune system to respond to a very wide variety of invaders, but may also give rise to lymphocytes capable of self-reactivity.

• HLA DR2 is strongly positively correlated with systemic lupus erythematosus, narcolepsy and multiple sclerosis, and negatively correlated with DM Type 1.
• HLA DR3 is correlated strongly with Sjögren syndrome, myasthenia gravis, SLE, and DM Type 1.
• HLA DR4 is correlated with the genesis of rheumatoid arthritis, Type 1 diabetes mellitus, and pemphigus vulgaris.

Fewer correlations exist with MHC class I molecules. The most notable and consistent is the association between HLA B27 and spondyloarthropathies like ankylosing spondylitis and reactive arthritis. Correlations may exist between polymorphisms within class II MHC promoters and autoimmune disease.

The contributions of genes outside the MHC complex remain the subject of research, in animal models of disease (Linda Wicker's extensive genetic studies of diabetes in the NOD mouse), and in patients (Brian Kotzin's linkage analysis of susceptibility to SLE).

Recently, PTPN22 has been associated with multiple autoimmune diseases including Type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, Hashimoto’s thyroiditis, Graves’ disease, Addison’s disease, Myasthenia Gravis, vitiligo, systemic sclerosis juvenile idiopathic arthritis, and psoriatic arthritis.

Sex

Ratio of female/male incidence of autoimmune diseases
Hashimoto's thyroiditis	10:1
Graves' disease	7:1
Multiple sclerosis (MS)	2:1
Myasthenia gravis	2:1
Systemic lupus erythematosus (SLE)	9:1
Rheumatoid arthritis	5:2
Primary sclerosing cholangitis	1:2

There is some evidence that a person's sex may also have some role in the development of autoimmunity; that is, most autoimmune diseases are sex-related. A few autoimmune diseases that men are just as or more likely to develop as women include: ankylosing spondylitis, type 1 diabetes mellitus, granulomatosis with polyangiitis, Crohn's disease, Primary sclerosing cholangitis and psoriasis.

The reasons for the sex role in autoimmunity vary. Women appear to generally mount larger inflammatory responses than men when their immune systems are triggered, increasing the risk of autoimmunity. Involvement of sex steroids is indicated by that many autoimmune diseases tend to fluctuate in accordance with hormonal changes, for example: during pregnancy, in the menstrual cycle, or when using oral contraception. A history of pregnancy also appears to leave a persistent increased risk for autoimmune disease. It has been suggested that the slight, direct exchange of cells between mothers and their children during pregnancy may induce autoimmunity. This would tip the gender balance in the direction of the female.

Another theory suggests the female high tendency to get autoimmunity is due to an imbalanced X-chromosome inactivation. The X-inactivation skew theory, proposed by Princeton University's Jeff Stewart, has recently been confirmed experimentally in scleroderma and autoimmune thyroiditis. Other complex X-linked genetic susceptibility mechanisms are proposed and under investigation.

Environmental factors

Infectious diseases and parasites

An interesting inverse relationship exists between infectious diseases and autoimmune diseases. In areas where multiple infectious diseases are endemic, autoimmune diseases are quite rarely seen. The reverse, to some extent, seems to hold true. The hygiene hypothesis attributes these correlations to the immune-manipulating strategies of pathogens. While such an observation has been variously termed as spurious and ineffective, according to some studies, parasite infection is associated with reduced activity of autoimmune disease.

The putative mechanism is that the parasite attenuates the host immune response in order to protect itself. This may provide a serendipitous benefit to a host that also suffers from autoimmune disease. The details of parasite immune modulation are not yet known, but may include secretion of anti-inflammatory agents or interference with the host immune signaling.

A paradoxical observation has been the strong association of certain microbial organisms with autoimmune diseases. For example, Klebsiella pneumoniae and coxsackievirus B have been strongly correlated with ankylosing spondylitis and diabetes mellitus type 1, respectively. This has been explained by the tendency of the infecting organism to produce super-antigens that are capable of polyclonal activation of B-lymphocytes, and production of large amounts of antibodies of varying specificities, some of which may be self-reactive (see below).

Chemical agents and drugs

Certain chemical agents and drugs can also be associated with the genesis of autoimmune conditions, or conditions that simulate autoimmune diseases. The most striking of these is the drug-induced lupus erythematosus. Usually, withdrawal of the offending drug cures the symptoms in a patient.

Cigarette smoking is now established as a major risk factor for both incidence and severity of rheumatoid arthritis. This may relate to abnormal citrullination of proteins, since the effects of smoking correlate with the presence of antibodies to citrullinated peptides.

Pathogenesis of autoimmunity

Several mechanisms are thought to be operative in the pathogenesis of autoimmune diseases, against a backdrop of genetic predisposition and environmental modulation. It is beyond the scope of this article to discuss each of these mechanisms exhaustively, but a summary of some of the important mechanisms have been described:

• T-cell bypass – A normal immune system requires the activation of B cells by T cells before the former can undergo differentiation into plasma B-cells and subsequently produce antibodies in large quantities. This requirement of a T cell can be bypassed in rare instances, such as infection by organisms producing super-antigens, which are capable of initiating polyclonal activation of B-cells, or even of T-cells, by directly binding to the β-subunit of T-cell receptors in a non-specific fashion.
• T-cell–B-cell discordance – A normal immune response is assumed to involve B and T cell responses to the same antigen, even if we know that B cells and T cells recognise very different things: conformations on the surface of a molecule for B cells and pre-processed peptide fragments of proteins for T cells. However, there is nothing as far as we know that requires this. All that is required is that a B cell recognising antigen X endocytoses and processes a protein Y (normally =X) and presents it to a T cell. Roosnek and Lanzavecchia showed that B cells recognising IgGFc could get help from any T cell responding to an antigen co-endocytosed with IgG by the B cell as part of an immune complex. In coeliac disease it seems likely that B cells recognising tissue transglutamine are helped by T cells recognising gliadin.
• Aberrant B cell receptor-mediated feedback – A feature of human autoimmune disease is that it is largely restricted to a small group of antigens, several of which have known signaling roles in the immune response (DNA, C1q, IgGFc, Ro, Con. A receptor, Peanut agglutinin receptor(PNAR)). This fact gave rise to the idea that spontaneous autoimmunity may result when the binding of antibody to certain antigens leads to aberrant signals being fed back to parent B cells through membrane bound ligands. These ligands include B cell receptor (for antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-like receptors 9 and 7 (which can bind DNA and nucleoproteins) and PNAR. More indirect aberrant activation of B cells can also be envisaged with autoantibodies to acetyl choline receptor (on thymic myoid cells) and hormone and hormone binding proteins. Together with the concept of T-cell–B-cell discordance this idea forms the basis of the hypothesis of self-perpetuating autoreactive B cells. Autoreactive B cells in spontaneous autoimmunity are seen as surviving because of subversion both of the T cell help pathway and of the feedback signal through B cell receptor, thereby overcoming the negative signals responsible for B cell self-tolerance without necessarily requiring loss of T cell self-tolerance.
• Molecular mimicry – An exogenous antigen may share structural similarities with certain host antigens; thus, any antibody produced against this antigen (which mimics the self-antigens) can also, in theory, bind to the host antigens, and amplify the immune response. The idea of molecular mimicry arose in the context of rheumatic fever, which follows infection with Group A beta-haemolytic streptococci. Although rheumatic fever has been attributed to molecular mimicry for half a century no antigen has been formally identified (if anything too many have been proposed). Moreover, the complex tissue distribution of the disease (heart, joint, skin, basal ganglia) argues against a cardiac specific antigen. It remains entirely possible that the disease is due to e.g. an unusual interaction between immune complexes, complement components and endothelium.
• Idiotype cross-reaction – Idiotypes are antigenic epitopes found in the antigen-binding portion (Fab) of the immunoglobulin molecule. Plotz and Oldstone presented evidence that autoimmunity can arise as a result of a cross-reaction between the idiotype on an antiviral antibody and a host cell receptor for the virus in question. In this case, the host-cell receptor is envisioned as an internal image of the virus, and the anti-idiotype antibodies can react with the host cells.
• Cytokine dysregulation – Cytokines have been recently divided into two groups according to the population of cells whose functions they promote: Helper T-cells type 1 or type 2. The second category of cytokines, which include IL-4, IL-10 and TGF-β (to name a few), seem to have a role in prevention of exaggeration of pro-inflammatory immune responses.
• Dendritic cell apoptosis – immune system cells called dendritic cells present antigens to active lymphocytes. Dendritic cells that are defective in apoptosis can lead to inappropriate systemic lymphocyte activation and consequent decline in self-tolerance.
• Epitope spreading or epitope drift – when the immune reaction changes from targeting the primary epitope to also targeting other epitopes. In contrast to molecular mimicry, the other epitopes need not be structurally similar to the primary one.
• Epitope modification or Cryptic epitope exposure – this mechanism of autoimmune disease is unique in that it does not result from a defect in the hematopoietic system. Instead, disease results from the exposure of cryptic N-glycan (polysaccharide) linkages common to lower eukaryotes and prokaryotes on the glycoproteins of mammalian non-hematopoietic cells and organs This exposure of phylogenically primitive glycans activates one or more mammalian innate immune cell receptors to induce a chronic sterile inflammatory state. In the presence of chronic and inflammatory cell damage, the adaptive immune system is recruited and self–tolerance is lost with increased autoantibody production. In this form of the disease, the absence of lymphocytes can accelerate organ damage, and intravenous IgG administration can be therapeutic. Although this route to autoimmune disease may underlie various degenerative disease states, no diagnostics for this disease mechanism exist at present, and thus its role in human autoimmunity is currently unknown.

The roles of specialized immunoregulatory cell types, such as regulatory T cells, NKT cells, γδ T-cells in the pathogenesis of autoimmune disease are under investigation.

Classification

Autoimmune diseases can be broadly divided into systemic and organ-specific or localised autoimmune disorders, depending on the principal clinico-pathologic features of each disease.

• Systemic autoimmune diseases include coeliac disease, lupus erythematosus, Sjögren syndrome, sarcoidosis, scleroderma, rheumatoid arthritis, cryoglobulinemic vasculitis, and dermatomyositis. These conditions tend to be associated with autoantibodies to antigens which are not tissue specific. Thus although polymyositis is more or less tissue specific in presentation, it may be included in this group because the autoantigens are often ubiquitous t-RNA synthetases.
• Local syndromes which affect a specific organ or tissue:
  • Endocrinologic: diabetes mellitus type 1, Hashimoto's thyroiditis, Addison's disease
  • Gastrointestinal: Crohn's disease, pernicious anaemia
  • Dermatologic: pemphigus vulgaris, vitiligo
  • Haematologic: autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura
  • Neurological: multiple sclerosis, myasthenia gravis, autoimmune encephalitis, gluten ataxia

Using the traditional “organ specific” and “non-organ specific” classification scheme, many diseases have been lumped together under the autoimmune disease umbrella. However, many chronic inflammatory human disorders lack the telltale associations of B and T cell driven immunopathology. In the last decade it has been firmly established that tissue "inflammation against self" does not necessarily rely on abnormal T and B cell responses.

This has led to the recent proposal that the spectrum of autoimmunity should be viewed along an “immunological disease continuum,” with classical autoimmune diseases at one extreme and diseases driven by the innate immune system at the other extreme. Within this scheme, the full spectrum of autoimmunity can be included. Many common human autoimmune diseases can be seen to have a substantial innate immune mediated immunopathology using this new scheme. This new classification scheme has implications for understanding disease mechanisms and for therapy development.

Diagnosis

Diagnosis of autoimmune disorders largely rests on accurate history and physical examination of the patient, and high index of suspicion against a backdrop of certain abnormalities in routine laboratory tests (example, elevated C-reactive protein).

In several systemic disorders, serological assays which can detect specific autoantibodies can be employed. Localised disorders are best diagnosed by immunofluorescence of biopsy specimens.

Autoantibodies are used to diagnose many autoimmune diseases. The levels of autoantibodies are measured to determine the progress of the disease.

Treatments

Treatments for autoimmune disease have traditionally been immunosuppressive, anti-inflammatory, or palliative. Managing inflammation is critical in autoimmune diseases. Non-immunological therapies, such as hormone replacement in Hashimoto's thyroiditis or Type 1 diabetes mellitus treat outcomes of the autoaggressive response, thus these are palliative treatments. Dietary manipulation limits the severity of celiac disease. Steroidal or NSAID treatment limits inflammatory symptoms of many diseases. IVIG is used for CIDP and GBS. Specific immunomodulatory therapies, such as the TNFα antagonists (e.g. etanercept), the B cell depleting agent rituximab, the anti-IL-6 receptor tocilizumab and the costimulation blocker abatacept have been shown to be useful in treating RA. Some of these immunotherapies may be associated with increased risk of adverse effects, such as susceptibility to infection.

Helminthic therapy is an experimental approach that involves inoculation of the patient with specific parasitic intestinal nematodes (helminths). There are currently two closely related treatments available, inoculation with either Necator americanus, commonly known as hookworms, or Trichuris Suis Ova, commonly known as Pig Whipworm Eggs.

T-cell vaccination is also being explored as a possible future therapy for autoimmune disorders.

Nutrition and autoimmunity

Vitamin D/Sunlight

• Because most human cells and tissues have receptors for vitamin D, including T and B cells, adequate levels of vitamin D can aid in the regulation of the immune system. Vitamin D plays a role in immune function by acting on T cells and natural killer cells.  Research has demonstrated an association between low serum vitamin D and autoimmune diseases, including multiple sclerosis, type 1 diabetes, and Systemic Lupus Erythematosus (commonly referred to simply as lupus).  However, since photosensitivity occurs in lupus, patients are advised to avoid sunlight which may be responsible for vitamin D deficiency seen in this disease. Polymorphisms in the vitamin D receptor gene are commonly found in people with autoimmune diseases, giving one potential mechanism for vitamin D's role in autoimmunity. There is mixed evidence on the effect of vitamin D supplementation in type 1 diabetes, lupus, and multiple sclerosis. 

Omega-3 Fatty Acids

• Studies have shown that adequate consumption of omega-3 fatty acids counteracts the effects of arachidonic acids, which contribute to symptoms of autoimmune diseases. Human and animal trials suggest that omega-3 is an effective treatment modality for many cases of Rheumatoid Arthritis, Inflammatory Bowel Disease, Asthma, and Psoriasis.
• While major depression is not necessarily an autoimmune disease, some of its physiological symptoms are inflammatory and autoimmune in nature. Omega-3 may inhibit production of interferon gamma and other cytokines which cause the physiological symptoms of depression. This may be due to the fact that an imbalance in omega-3 and omega-6 fatty acids, which have opposing effects, is instrumental in the etiology of major depression.

Probiotics/Microflora

• Various types of bacteria and microflora present in fermented dairy products, especially Lactobacillus casei, have been shown to both stimulate immune response to tumors in mice and to regulate immune function, delaying or preventing the onset of nonobese diabetes. This is particularly true of the Shirota strain of L. casei (LcS). The LcS strain is mainly found in yogurt and similar products in Europe and Japan, and rarely elsewhere.

Antioxidants

• It has been theorized that free radicals contribute to the onset of type-1 diabetes in infants and young children, and therefore that the risk could be reduced by high intake of antioxidant substances during pregnancy. However, a study conducted in a hospital in Finland from 1997-2002 concluded that there was no statistically significant correlation between antioxidant intake and diabetes risk. This study involved monitoring of food intake through questionnaires, and estimated antioxidant intake on this basis, rather than by exact measurements or use of supplements.

自體免疫性疾病

自體免疫性疾病

自體免疫性疾病

Autoimmune diseases
Young woman with the typical "butterfly rash" found in systemic lupus erythematosus
症状	Depends on the condition. Commonly low grade fever, feeling tired
起病年龄	Adulthood
类型	List of autoimmune diseases (alopecia areata, celiac disease, diabetes mellitus type 1, Graves' disease, inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, others)
藥物	Nonsteroidal anti-inflammatory drugs, immunosuppressants, intravenous immunoglobulin
患病率	24 million / 7% (USA)
分类和外部资源
醫學專科	Rheumatology, immunology, gastroenterology, neurology, dermatology

An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. Often symptoms come and go.

The cause is generally unknown. Some autoimmune diseases such as lupus run in families, and certain cases may be triggered by infections or other environmental factors. Some common diseases that are generally considered autoimmune include celiac disease, diabetes mellitus type 1, Graves' disease, inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. The diagnosis can be difficult to determine.

Treatment depends on the type and severity of the condition. Nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are often used. Intravenous immunoglobulin may also occasionally be used. While treatment usually improves symptoms, they do not typically cure the disease.

About 24 million (7%) people in the United States are affected by an autoimmune disease. Women are more commonly affected than men. Often they start during adulthood. The first autoimmune diseases were described in the early 1900s.

Signs and symptoms

Rheumatoid arthritis

Autoimmune diseases have a wide variety of different effects. They do tend to have one of three characteristic pathological effects which characterize them as autoimmune diseases:

1. Damage to or destruction of tissues
2. Altered organ growth
3. Altered organ function

It has been estimated that autoimmune diseases are among the leading causes of death among women in the United States in all age groups up to 65 years.

A substantial minority of the population suffers from these diseases, which are often chronic, debilitating, and life-threatening.

There are more than 80 illnesses caused by autoimmunity.

Causes

The cause is generally unknown. Some autoimmune diseases such as lupus run in families, and certain cases may be triggered by infections or other environmental factors. There are more than 100 autoimmune diseases. Some common diseases that are generally considered autoimmune include celiac disease, diabetes mellitus type 1, Graves' disease, inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus.

Pathophysiology

The human immune system typically produces both T cells and B cells that are capable of being reactive with self-antigens, but these self-reactive cells are usually either killed prior to becoming active within the immune system, placed into a state of anergy (silently removed from their role within the immune system due to over-activation), or removed from their role within the immune system by regulatory cells. When any one of these mechanisms fail, it is possible to have a reservoir of self-reactive cells that become functional within the immune system. The mechanisms of preventing self-reactive T cells from being created takes place through negative selection process within the thymus as the T cell is developing into a mature immune cell.

Some infections, such as Campylobacter jejuni, have antigens that are similar (but not identical) to our own self-molecules. In this case, a normal immune response to C. jejuni can result in the production of antibodies that also react to a lesser degree with gangliosides of myelin sheath surrounding peripheral nerves' axons (i.e., Guillain–Barré). A major understanding of the underlying pathophysiology of autoimmune diseases has been the application of genome wide association scans that have identified a degree of genetic sharing among the autoimmune diseases.

Autoimmunity, on the other hand, is the presence of self-reactive immune response (e.g., auto-antibodies, self-reactive T cells), with or without damage or pathology resulting from it. This may be restricted to certain organs (e.g. in autoimmune thyroiditis) or involve a particular tissue in different places (e.g. Goodpasture's disease which may affect the basement membrane in both the lung and the kidney).

There are many theories as to how an autoimmune disease state arises. Some common ones are listed below.

Cryptic determinants/molecular sequestration

Although it is possible for a potential autoantigen to be spatially sequestered in an immune privileged site within the body (e.g. the eye), mechanisms exist to express even these antigens in a tolerogenic fashion to the immune system. However, it is impossible to induce tolerance (immune unresponsiveness) to all aspects of an autoantigen. This is because under normal physiologic conditions some regions of a self-antigen are not expressed at a sufficient level to induce tolerance. These poorly displayed areas of an antigen are called "cryptic determinants." The immune system maintains a high-affinity repertoire to the cryptic self because the presentation of these determinants was insufficient to induce strong tolerance.

Molecular mimicry

The concept of molecular mimicry describes a situation in which a foreign antigen can initiate an immune response in which a T or B cell component cross-recognizes self. The cross reactive immune response is responsible for the autoimmune disease state. Cross-reactive immune responses to self were first described for antibodies.

Altered glycan theory

According to this theory the effector function of the immune response is mediated by the glycans (polysaccharides) displayed by the cells and humoral components of the immune system. Individuals with autoimmunity have alterations in their glycosylation profile such that a proinflammatory immune response is favored. It is further hypothesized that individual autoimmune diseases will have unique glycan signatures.

Hygiene hypothesis

According to the hygiene hypothesis, high levels of cleanliness expose children to fewer antigens than in the past, causing their immune systems to become overactive and more likely to misidentify own tissues as foreign, resulting in autoimmune or allergic conditions such as asthma.

Diagnosis

For a disease to be regarded as an autoimmune disease it needs to answer to Witebsky's postulates (first formulated by Ernest Witebsky and colleagues in 1957 and modified in 1994):

• Direct evidence from transfer of disease-causing antibody or disease-causing T lymphocyte white blood cells
• Indirect evidence based on reproduction of the autoimmune disease in experimental animals
• Circumstantial evidence from clinical clues

Epidemiology

The first estimate of US prevalence for autoimmune diseases as a group was published in 1997 by Jacobson, et al. They reported US prevalence to be around 9 million, applying prevalence estimates for 24 diseases to a US population of 279 million. Jacobson's work was updated by Hayter & Cook in 2012. This study used Witebsky's postulates, as revised by Rose & Bona, to extend the list to 81 diseases and estimated overall cumulative US prevalence for the 81 autoimmune diseases at 5.0%, with 3.0% for males and 7.1% for females. The estimated community prevalence, which takes into account the observation that many people have more than one autoimmune disease, was 4.5% overall, with 2.7% for males and 6.4% for females.

Research

In both autoimmune and inflammatory diseases, the condition arises through aberrant reactions of the human adaptive or innate immune systems. In autoimmunity, the patient's immune system is activated against the body's own proteins. In chronic inflammatory diseases, neutrophils and other leukocytes are constitutively recruited by cytokines and chemokines, leading to tissue damage.

Mitigation of inflammation by activation of anti-inflammatory genes and the suppression of inflammatory genes in immune cells is a promising therapeutic approach. There is a body of evidence that once the production of autoantibodies has been initialized, autoantibodies have the capacity to maintain their own production.

Stem cell transplantation is being studied and has shown promising results in certain cases.

History

Traditionally it was believed that the immune system was unable to react against the body's own tissues, a concept described by the German immunologist Paul Ehrlich as "horror autotoxicus". In 1904 this theory was challenged by the discovery of a substance in the serum of patients with paroxysmal cold hemoglobinuria that reacted with red blood cells.

單株抗體治療

單株抗體治療 單克隆抗體治療 Template:細胞外化療藥物 en:Biologics for immunosuppression

單株抗體治療

Antibody structure and function

更多信息：Monoclonal antibodies

Immunoglobulin G (IgG) antibodies are large heterodimeric molecules, approximately 150 kDa and are composed of two kinds of polypeptide chain, called the heavy (~50kDa) and the light chain (~25kDa). The two types of light chains are kappa (κ) and lambda (λ). By cleavage with enzyme papain, the Fab (fragment-antigen binding) part can be separated from the Fc (fragment constant) part of the molecule. The Fab fragments contain the variable domains, which consist of three antibody hypervariable amino acid domains responsible for the antibody specificity embedded into constant regions. The four known IgG subclasses are involved in antibody-dependent cellular cytotoxicity. Antibodies are a key component of the adaptive immune response, playing a central role in both in the recognition of foreign antigens and the stimulation of an immune response to them. The advent of monoclonal antibody technology has made it possible to raise antibodies against specific antigens presented on the surfaces of tumors. Monoclonal antibodies can be acquired in the immune system via passive immunity or active immunity.The advantage of active monoclonal antibody therapy is the fact that the immune system will produce antibodies long-term, with only a short-term drug administration to induce this response. However, the immune response to certain antigens may be inadequate, especially in the elderly. Additionally, adverse reactions from these antibodies may occur because of long-lasting response to antigens. Passive monoclonal antibody therapy can ensure consistent antibody concentration, and can control for adverse reactions by stopping administration. However, the repeated administration and consequent higher cost for this therapy are major disadvantages.

Monoclonal antibody therapy may prove to be beneficial for cancer, autoimmune diseases, and neurological disorders that result in the degeneration of body cells, such as Alzheimer's disease. Monoclonal antibody therapy can aid the immune system because the innate immune system responds to the environmental factors it encounters by discriminating against foreign cells from cells of the body. Therefore, tumor cells that are proliferating at high rates, or body cells that are dying which subsequently cause physiological problems are generally not specifically targeted by the immune system, since tumor cells are the patient's own cells. Tumor cells, however are highly abnormal, and many display unusual antigens. Some such tumor antigens are inappropriate for the cell type or its environment. Monoclonal antibodies can target tumor cells or abnormal cells in the body that are recognized as body cells, but are debilitating to one's health.

History

Monoclonal antibodies for cancer. ADEPT: antibody directed enzyme prodrug therapy; ADCC: antibody-dependent cell-mediated cytotoxicity; CDC: complement-dependent cytotoxicity; MAb, monoclonal antibody; scFv, single-chain Fv fragment.

Immunotherapy developed in the 1970s following the discovery of the structure of antibodies and the development of hybridoma technology, which provided the first reliable source of monoclonal antibodies. These advances allowed for the specific targeting of tumors both in vitro and in vivo. Initial research on malignant neoplasms found mAb therapy of limited and generally short-lived success with blood malignancies. Treatment also had to be tailored to each individual patient, which was impracticable in routine clinical settings.

Four major antibody types that have been developed are murine, chimeric, humanised and human. Antibodies of each type are distinguished by suffixes on their name.

Murine

Initial therapeutic antibodies were murine analogues (suffix -omab). These antibodies have: a short half-life in vivo (due to immune complex formation), limited penetration into tumour sites and inadequately recruit host effector functions. Chimeric and humanized antibodies have generally replaced them in therapeutic antibody applications. Understanding of proteomics has proven essential in identifying novel tumour targets.

Initially, murine antibodies were obtained by hybridoma technology, for which Jerne, Köhler and Milstein received a Nobel prize. However the dissimilarity between murine and human immune systems led to the clinical failure of these antibodies, except in some specific circumstances. Major problems associated with murine antibodies included reduced stimulation of cytotoxicity and the formation complexes after repeated administration, which resulted in mild allergic reactions and sometimes anaphylactic shock. Hybridoma technology has been replaced by recombinant DNA technology, transgenic mice and phage display.

Chimeric and humanized

To reduce murine antibody immunogenicity (attacks by the immune system against the antibody), murine molecules were engineered to remove immunogenic content and to increase immunologic efficiency. This was initially achieved by the production of chimeric (suffix -ximab) and humanized antibodies (suffix -zumab). Chimeric antibodies are composed of murine variable regions fused onto human constant regions. Taking human gene sequences from the kappa light chain and the IgG1 heavy chain results in antibodies that are approximately 65% human. This reduces immunogenicity, and thus increases serum half-life.

Humanised antibodies are produced by grafting murine hypervariable regions on amino acid domains into human antibodies. This results in a molecule of approximately 95% human origin. Humanised antibodies bind antigen much more weakly than the parent murine monoclonal antibody, with reported decreases in affinity of up to several hundredfold. Increases in antibody-antigen binding strength have been achieved by introducing mutations into the complementarity determining regions (CDR), using techniques such as chain-shuffling, randomization of complementarity-determining regions and antibodies with mutations within the variable regions induced by error-prone PCR, E. coli mutator strains and site-specific mutagenesis.

Human monoclonal antibodies

Human monoclonal antibodies (suffix -umab) are produced using transgenic mice or phage display libraries by transferring human immunoglobulin genes into the murine genome and vaccinating the transgenic mouse against the desired antigen, leading to the production of appropriate monoclonal antibodies. Murine antibodies in vitro are thereby transformed into fully human antibodies.

The heavy and light chains of human IgG proteins are expressed in structural polymorphic (allotypic) forms. Human IgG allotype is one of the many factors that can contribute to immunogenicity.

Targeted conditions

Cancer

Anti-cancer monoclonal antibodies can be targeted against malignant cells by several mechanisms. Ramucirumab is a recombinant human monoclonal antibody and is used in the treatment of advanced malignancies. In childhood lymphoma, phase I and II studies have found a positive effect of using antibody therapy.

Autoimmune diseases

Monoclonal antibodies used for autoimmune diseases include infliximab and adalimumab, which are effective in rheumatoid arthritis, Crohn's disease and ulcerative colitis by their ability to bind to and inhibit TNF-α. Basiliximab and daclizumab inhibit IL-2 on activated T cells and thereby help preventing acute rejection of kidney transplants. Omalizumab inhibits human immunoglobulin E (IgE) and is useful in moderate-to-severe allergic asthma.

Alzheimer's disease

Alzheimer’s disease (AD) is a multi-faceted, age-dependent, progressive neurodegenerative disorder, and is a major cause of dementia. According to the Amyloid hypothesis, the accumulation of extracellular amyloid betapeptides (Aβ) into plaques via oligomerization leads to hallmark symptomatic conditions of AD through synaptic dysfunction and neurodegeneration. Immunotherapy via exogenous monoclonal antibody (MAB) administration has been known to treat various central nervous disorders, such as AD, by inhibiting Aβ-oligomerization thereby preventing neurotoxicity. However, MABs are large for passive protein channels and are therefore inefficient due to the blood-brain barrier preventing MAB passage into the brain. However, the Peripheral Sink hypothesis proposes a mechanism where MABs may not need to cross the blood-brain barrier. Therefore, many research studies are being conducted from failed attempts to treat AD in the past.

However, anti-Aβ vaccines can promote antibody-mediated clearance of Aβ plaques in transgenic mice models with amyloid precursor proteins (APP), and can reduce cognitive impairments. Vaccines can stimulate the immune system to produce its own antibodies, in this case by introducing Aβ into transgenic animal models, known as active immunization. They can also introduce antibodies into animal models, known as passive immunization. In mice expressing APP, both active and passive immunization of anti-Aβ antibodies has been shown to be effective in clearing plaques, and can improve cognitive function.. Therefore, several clinical trials using passive and active immunization approaches by development of certain drugs approved by the FDA are currently underway, and are expected to yield results in a couple of years. The implementation of these drugs is during the onset of AD. Other research and drug development for early intervention and AD prevention is ongoing. Various drugs that are under research to treat AD include Bapineuzumab, Solanezumab, and Gautenerumab.

Bapineuzumab

Bapineuzumab, a humanized anti-aβ MAB, is directed against the N-terminus of Aβ. Phase II clinical trials of Bapineuzumab in mild to moderate AD patients resulted in reduced Aβ concentration in the brain. However, in patients with increased apolipoprotein (APOE) e4 carriers, Bapineuzumab treatment is also accompanied by vasogenic edema, a cytotoxic condition where the blood brain barrier has been disrupted thereby affecting white matter from excess accumulation of fluid from capillaries in intracellular and extracellular spaces of the brain. In Phase III clinical trials, Bapineuzumab treatment is associated with reduced rate of accumulation of Aβ in the brain in APOE e4 patients, and no significant reduction of Aβ concentration in APOE e4 patients and non-APOE e4 patients. Therefore, Aβ plaque concentration was not reduced, and there is no significant clinical benefits in cognitive functioning. Bapineuzumab was discontinued after failing in Phase III clinical trial

Solanezumab

Solanezumab, an anti-aβ MAB, targets the N-terminus of Aβ. In Phase I and Phase II of clinical trials, Solanezumab treatment resulted in cerebrospinal fluid elevation of Aβ, thereby showing a reduced concentration of Aβ plaques. Additionally, there are no associated adverse side effects. Phase III clinical trials of Solanezumab brought about significant reduction in cognitive impairment in patients with mild AD, but not in patients with severe AD. However, Aβ concentration did not significantly change, along with other AD biomarkers, including phospho-tau expression, and hippocampal volume. Phase III clinical trials are currently ongoing.

Preventive trials

Failure of several drugs in Phase III clinical trials has led to AD prevention and early intervention for onset AD treatment endeavours. Passive anti-Aβ MAB treatment can be used for preventive attempts to modify AD progression before it causes extensive brain damage and symptoms. Trials using MAB treatment for patients positive for genetic risk factors, and elderly patients positive for indicators of AD are underway. This includes anti-AB treatment in Asymptomatic Alzheimer's Disease (A4), the Alzheimer’s Prevention Initiative (API), and DIAN-TU. The A4 study on older individuals who are positive for indicators of AD but are negative for genetic risk factors will test Solanezumab in Phase III Clinical Trials, as a follow up of previous Solanezumab studies. DIAN-TU, launched in December 2012, focuses on young patients positive for genetic mutations that are risks for AD. This study uses Solanezumab and Gautenerumab. Gautenerumab, the first fully human MAB that preferentially interacts with oligomerized Aβ plaques in the brain, caused significant reduction in Aβ concentration in Phase I clinical trials, preventing plaque formation and concentration without altering plasma concentration of the brain. Phase II and III clinical trials are currently being conducted.

Therapy types

Radioimmunotherapy

Radioimmunotherapy (RIT) involves the use of radioactively-conjugated murine antibodies against cellular antigens. Most research involves their application to lymphomas, as these are highly radio-sensitive malignancies. To limit radiation exposure, murine antibodies were chosen, as their high immunogenicity promotes rapid tumor clearance. Tositumomab is an example used for non-Hodgkin's lymphoma.

Antibody-directed enzyme prodrug therapy

Antibody-directed enzyme prodrug therapy (ADEPT) involves the application of cancer-associated monoclonal antibodies that are linked to a drug-activating enzyme. Systemic administration of a non-toxic agent results in the antibody's conversion to a toxic drug, resulting in a cytotoxic effect that can be targeted at malignant cells. The clinical success of ADEPT treatments is limited.

Antibody-drug conjugates

Antibody-drug conjugates (ADCs) are antibodies linked to one or more drug molecules. Typically when the ADC meets the target cell (e.g. a cancerous cell) the drug is released to kill it. Many ADCs are in clinical development. 截至2016年 (2016-Missing required parameter 1=month!) a few have been approved.

Immunoliposome therapy

Immunoliposomes are antibody-conjugated liposomes. Liposomes can carry drugs or therapeutic nucleotides and when conjugated with monoclonal antibodies, may be directed against malignant cells. Immunoliposomes have been successfully used in vivo to convey tumour-suppressing genes into tumours, using an antibody fragment against the human transferrin receptor. Tissue-specific gene delivery using immunoliposomes has been achieved in brain and breast cancer tissue.

Checkpoint therapy

Checkpoint therapy uses antibodies and other techniques to circumvent the defenses that tumors use to suppress the immune system. Each defense is known as a checkpoint. Compound therapies combine antibodies to suppress multiple defensive layers. Known checkpoints include CTLA-4 targeted by ipilimumab, PD-1 targeted by nivolumab and pembrolizumab and the tumor microenvironment.

The tumor microenvironment (TME) features prevents the recruitment of T cells to the tumor. Ways include chemokine CCL² nitration, which traps T cells in the stroma. Tumor vasculature helps tumors preferentially recruit other immune cells over T cells, in part through endothelial cell (EC)–specific expression of FasL, ET_BR, and B7H3. Myelomonocytic and tumor cells can up-regulate expression of PD-L1, partly driven by hypoxic conditions and cytokine production, such as IFNβ. Aberrant metabolite production in the TME, such as the pathway regulation by IDO, can affect T cell functions directly and indirectly via cells such as T_reg cells. CD8 cells can be suppressed by B cells regulation of TAM phenotypes. Cancer-associated fibroblasts (CAFs) have multiple TME functions, in part through extracellular matrix (ECM)–mediated T cell trapping and CXCL12-regulated T cell exclusion.

FDA-approved therapeutic antibodies

The first FDA-approved therapeutic monoclonal antibody was a murine IgG2a CD3 specific transplant rejection drug, OKT3 (also called muromonab), in 1986. This drug found use in solid organ transplant recipients who became steroid resistant. Hundreds of therapies are undergoing clinical trials. Most are concerned with immunological and oncological targets.

FDA approved therapeutic monoclonal antibodies

Antibody	Brand name	Company	Approval date	Route	Type	Target	Indication (Targeted disease)	BLA STN	Drug Label
abciximab	ReoPro	Centocor	12/22/1994	intravenous	chimeric Fab	GPIIb/IIIa	Percutaneous coronary intervention	103575	Link
adalimumab	Humira	Abbvie	12/31/2002	subcutaneous	fully human	TNF	Rheumatoid arthritis	125057	Link
adalimumab-atto	Amjevita	Amgen	9/23/2016	subcutaneous	fully human, biosimilar	TNF	Rheumatoid arthritis Juvenile idiopathic arthritis Psoriatic arthritis Ankylosing spondylitis Crohn's disease Ulcerative colitis Plaque psoriasis	761024	Link
ado-trastuzumab emtansine	Kadcyla	Genentech	2/22/2013	intravenous	humanized, antibody-drug conjugate	HER2	Metastatic breast cancer	125427	Link
alemtuzumab	Campath, Lemtrada	Genzyme	5/7/2001	intravenous	humanized	CD52	B-cell chronic lymphocytic leukemia	103948	Link
alirocumab	Praluent	Sanofi Aventis	7/24/2015	subcutaneous	fully human	PCSK9	Heterozygous familial hypercholesterolemia Refractory hypercholesterolemia	125559	Link
atezolizumab	Tecentriq	Genentech	5/18/2016	intravenous	humanized	PD-L1	Urothelial carcinoma	761034	Link
atezolizumab	Tecentriq	Genentech	10/18/2016	intravenous	humanized	PD-L1	Urothelial carcinoma Metastatic non-small cell lung cancer	761041	Link
avelumab	Bavencio	EMD Serono	3/23/2017	intravenous	fully human	PD-L1	Metastatic Merkel cell carcinoma	761049	Link
basiliximab	Simulect	Novartis	5/12/1998	intravenous	chimeric	IL2RA	Prophylaxis of acute organ rejection in renal transplant	103764	Link
belimumab	Benlysta	Human Genome Sciences	3/9/2011	intravenous	fully human	BLyS	Systemic lupus erythematosus	125370	Link
bevacizumab	Avastin	Genentech	2/26/2004	intravenous	humanized	VEGF	Metastatic colorectal cancer	125085	Link
bezlotoxumab	Zinplava	Merck	10/21/2016	intravenous	fully human	Clostridium difficile toxin B	Prevent recurrence of Clostridium difficile infection	761046	Link
blinatumomab	Blincyto	Amgen	12/3/2014	intravenous	mouse, bispecific	CD19	Precursor B-cell acute lymphoblastic leukemia	125557	Link
brentuximab vedotin	Adcetris	Seattle Genetics	9/19/2011	intravenous	chimeric, antibody-drug conjugate	CD30	Hodgkin lymphoma Anaplastic large-cell lymphoma	125388	Link
brodalumab	Siliq	Valeant	2/15/2017	subcutaneous	chimeric	IL17RA	Plaque psoriasis	761032	Link
canakinumab	Ilaris	Novartis	6/17/2009	subcutaneous	fully human	IL1B	Cryopyrin-associated periodic syndrome	125319	Link
capromab pendetide	ProstaScint	Cytogen	10/28/1996	intravenous	murine, radiolabeled	PSMA	Diagnostic imaging agent in newly diagnosed prostate cancer or post-prostatectomy	103608	Link
certolizumab pegol	Cimzia	UCB (company)	4/22/2008	subcutaneous	humanized	TNF	Crohn's disease	125160	Link
cetuximab	Erbitux	ImClone Systems	2/12/2004	intravenous	chimeric	EGFR	Metastatic colorectal carcinoma	125084	Link
daclizumab	Zenapax	Roche	12/10/1997	intravenous	humanized	IL2RA	Prophylaxis of acute organ rejection in renal transplant	103749	Link
daclizumab	Zinbryta	Biogen	5/27/2016	subcutaneous	humanized	IL2R	Multiple sclerosis	761029	Link
daratumumab	Darzalex	Janssen Biotech	11/16/2015	intravenous	fully human	CD38	Multiple myeloma	761036	Link
denosumab	Prolia, Xgeva	Amgen	6/1/2010	subcutaneous	fully human	RANKL	Postmenopausal women with osteoporosis	125320	Link
dinutuximab	Unituxin	United Therapeutics	3/10/2015	intravenous	chimeric	GD2	Pediatric high-risk neuroblastoma	125516	Link
dupilumab	Dupixent	Regeneron Pharmaceuticals	3/28/2017	subcutaneous	fully human	IL4RA	Atopic dermatitis, asthma	761055	Link
durvalumab	Imfinzi	AstraZeneca	5/1/2017	intravenous	fully human	PD-L1	Urothelial carcinoma	761069	Link
eculizumab	Soliris	Alexion	3/16/2007	intravenous	humanized	Complement component 5	Paroxysmal nocturnal hemoglobinuria	125166	Link
elotuzumab	Empliciti	Bristol-Myers Squibb	11/30/2015	intravenous	humanized	SLAMF7	Multiple myeloma	761035	Link
evolocumab	Repatha	Amgen	8/27/2015	subcutaneous	fully human	PCSK9	Heterozygous familial hypercholesterolemia Refractory hypercholesterolemia	125522	Link
golimumab	Simponi	Centocor	4/24/2009	subcutaneous	fully human	TNF	Rheumatoid arthritis Psoriatic arthritis Ankylosing spondylitis	125289	Link
golimumab	Simponi Aria	Janssen Biotech	7/18/2013	intravenous	fully human	TNF	Rheumatoid arthritis	125433	Link
ibritumomab tiuxetan	Zevalin	Spectrum Pharmaceuticals	2/19/2002	intravenous	murine, radioimmunotherapy	CD20	Relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma	125019	Link
idarucizumab	Praxbind	Boehringer Ingelheim	10/16/2015	intravenous	humanized Fab	dabigatran	Emergency reversal of anticoagulant dabigatran	761025	Link
infliximab	Remicade	Centocor	8/24/1998	intravenous	chimeric	TNF alpha	Crohn's disease	103772	Link
infliximab-abda	Renflexis	Samsung Bioepis	4/21/2017	intravenous	chimeric, biosimilar	TNF	Crohn's disease Ulcerative colitis Rheumatoid arthritis Ankylosing spondylitis Psoriatic arthritis Plaque psoriasis	761054	Link
infliximab-dyyb	Inflectra	Celltrion Healthcare	4/5/2016	intravenous	chimeric, biosimilar	TNF	Crohn's disease Ulcerative colitis Rheumatoid arthritis Ankylosing spondylitis Psoriatic arthritis Plaque psoriasis	125544	Link
ipilimumab	Yervoy	Bristol-Myers Squibb	3/25/2011	intravenous	fully human	CTLA-4	Metastatic melanoma	125377	Link
ixekizumab	Taltz	Eli Lilly	3/22/2016	subcutaneous	humanized	IL17A	Plaque psoriasis	125521	Link
mepolizumab	Nucala	GlaxoSmithKline	11/4/2015	subcutaneous	humanized	IL5	Severe asthma	125526	Link
natalizumab	Tysabri	Biogen Idec	11/23/2004	intravenous	humanized	alpha-4 integrin	Multiple sclerosis	125104	Link
necitumumab	Portrazza	Eli Lilly	11/24/2015	intravenous	fully human	EGFR	Metastatic squamous non-small cell lung carcinoma	125547	Link
nivolumab	Opdivo	Bristol-Myers Squibb	12/22/2014	intravenous	fully human	PD-1	Metastatic melanoma	125554	Link
nivolumab	Opdivo	Bristol-Myers Squibb	3/4/2015	intravenous	fully human	PD-1	Metastatic squamous non-small cell lung carcinoma	125527	Link
obiltoxaximab	Anthem	Elusys Therapeutics	3/18/2016	intravenous	chimeric	Protective antigen of the Anthrax toxin	Inhalational anthrax	125509	Link
obinutuzumab	Gazyva	Genentech	11/1/2013	intravenous	humanized	CD20	Chronic lymphocytic leukemia	125486	Link
ocrelizumab	Ocrevus	Genentech	3/28/2017	intravenous	humanized	CD20	Multiple sclerosis	761053	Link
ofatumumab	Arzerra	Glaxo Grp	10/26/2009	intravenous	fully human	CD20	Chronic lymphocytic leukemia	125326	Link
olaratumab	Lartruvo	Eli Lilly	10/19/2016	intravenous	fully human	PDGFRA	Soft tissue sarcoma	761038	Link
omalizumab	Xolair	Genentech	6/20/2003	subcutaneous	humanized	IgE	Moderate to severe persistent asthma	103976	Link
palivizumab	Synagis	MedImmune	6/19/1998	intramuscular	humanized	F protein of RSV	Respiratory syncytial virus	103770	Link
panitumumab	Vectibix	Amgen	9/27/2006	intravenous	fully human	EGFR	Metastatic colorectal cancer	125147	Link
pembrolizumab	Keytruda	Merck	9/4/2014	intravenous	humanized	PD-1	Metastatic melanoma	125514	Link
pertuzumab	Perjeta	Genentech	6/8/2012	intravenous	humanized	HER2	Metastatic breast cancer	125409	Link
ramucirumab	Cyramza	Eli Lilly	4/21/2014	intravenous	fully human	VEGFR2	Gastric cancer	125477	Link
ranibizumab	Lucentis	Genentech	6/30/2006	intravitreal injection	humanized	VEGFR1 VEGFR2	Wet age-related macular degeneration	125156	Link
raxibacumab	Raxibacumab	Human Genome Sciences	12/24/2012	intravenous	fully human	Protective antigen of Bacillus anthracis	Inhalational anthrax	125349	Link
reslizumab	Cinqair	Teva	3/23/2016	intravenous	humanized	IL5	Severe asthma	761033	Link
rituximab	Rituxan	Genentech	11/26/1997	intravenous	chimeric	CD20	B-cell non-Hodgkin's lymphoma	103705	Link
secukinumab	Cosentyx	Novartis	1/21/2015	subcutaneous	fully human	IL17A	Plaque psoriasis	125504	Link
siltuximab	Sylvant	Janssen Biotech	4/23/2014	intravenous	chimeric	IL6	Multicentric Castleman's disease	125496	Link
tocilizumab	Actemra	Genentech	1/8/2010	intravenous	humanized	IL6R	Rheumatoid arthritis	125276	Link
tocilizumab	Actemra	Genentech	10/21/2013	intravenous subcutaneous	humanized	IL6R	Rheumatoid arthritis Polyarticular juvenile idiopathic arthritis Systemic juvenile idiopathic arthritis	125472	Link
trastuzumab	Herceptin	Genentech	9/25/1998	intravenous	humanized	HER2	Metastatic breast cancer	103792	Link
ustekinumab	Stelara	Centocor	9/25/2009	subcutaneous	fully human	IL12 IL23	Plaque psoriasis	125261	Link
ustekinumab	Stelara	Janssen Biotech	9/23/2016	subcutaneous intravenous	fully human	IL12 IL23	Plaque psoriasis Psoriatic arthritis Crohn's disease	761044	Link
vedolizumab	Entyvio	Takeda	5/20/2014	intravenous	humanized	integrin receptor	Ulcerative colitis Crohn's disease	125476	Link
sarilumab	Kevzara	Sanofi Aventis	5/22/17	subcutaneous	fully human	IL6R	Rheumatoid arthritis	761037	Link
rituximab and hyaluronidase	Rituxan Hycela	Genentech	6/22/17	subcutaneous	chimeric, co-formulated	CD20	Follicular lymphoma Diffuse large B-cell lymphoma Chronic lymphocytic leukemia	761064	Link
guselkumab	Tremfya	Janssen Biotech	7/13/17	subcutaneous	fully human	IL23	Plaque psoriasis	761061	Link
inotuzumab ozogamicin	Besponsa	Wyeth	8/17/17	intravenous	humanized, antibody-drug conjugate	CD22	Precursor B-cell acute lymphoblastic leukemia	761040	Link
adalimumab-adbm	Cyltezo	Boehringer Ingelheim	8/25/17	subcutaneous	fully human, biosimilar	TNF	Rheumatoid arthritis Juvenile idiopathic arthritis Psoriatic arthritis Ankylosing spondylitis Crohn's disease Ulcerative colitis Plaque psoriasis	761058	Link
gemtuzumab ozogamicin	Mylotarg	Wyeth	9/1/17	intravenous	humanized, antibody-drug conjugate	CD33	Acute myeloid leukemia	761060	Link
bevacizumab-awwb	Mvasi	Amgen	9/14/17	intravenous	humanized, biosimilar	VEGF	Metastatic colorectal cancer Non-squamous Non-small-cell lung carcinoma Glioblastoma Metastatic renal cell carcinoma Cervical cancer	761028	Link
benralizumab	Fasenra	Astrazeneca	11/14/17	subcutaneous	humanized	interleukin-5 receptor alpha subunit	Severe asthma, eosinophilic phenotype	761070	Link
emicizumab-kxwh	Hemlibra	Genentech	11/16/17	subcutaneous	humanized, bispecific	Factor IXa, Factor X	Hemophilia A (congenital Factor VIII deficiency) with Factor VIII inhibitors.	761083	Link
trastuzumab-dkst	Ogivri	Mylan	12/1/17	intravenous	humanized, biosimilar	HER2	HER2-overexpressing breast cancer, metaststic gastric or gastroesophageal junction adenocarcinoma	761074	Link
infliximab-qbtx	Ixifi	Pfizer	12/13/17	intravenous	chimeric, biosimilar	TNF	Crohn's disease Ulcerative colitis Rheumatoid arthritis Ankylosing spondylitis Psoriatic arthritis Plaque psoriasis	761072	Link
ibalizumab-uiyk	Trogarzo	TaiMed Biologics	3/6/18	intravenous	humanized	CD4	HIV	761065	Link
tildrakizumab-asmn	Ilumya	Merck	3/20/18	subcutaneous	humanized	IL23	Plaque psoriasis	761067	Link
burosumab-twza	Crysvita	Ultragenyx	4/17/18	subcutaneous	fully human	FGF23	X-linked hypophosphatemia	761068	Link
erenumab-aooe	Aimovig	Amgen	5/17/18	subcutaneous	fully human	CGRP receptor	Migraine headache prevention	761077	Link

Tositumomab - Bexxar - 2003 - CD20

Mogamulizumab - Poteligeo - August 2018 - CCR4

Moxetumomab pasudotox - Lumoxiti - Sept 2018 - CD22

Cemiplimab - Libtayo - Sept 2018 - PD-1

Polatuzumab vedotin - Polivy - June 2019 - CD79B

Recently, the bispecific antibodies, a novel class of therapeutic antibodies, have yielded promising results in clinical trials. In April 2009, the bispecific antibody catumaxomab was approved in the European Union.

Economics

Since 2000, the therapeutic market for monoclonal antibodies has grown exponentially. In 2006, the “big 5” therapeutic antibodies on the market were bevacizumab, trastuzumab (both oncology), adalimumab, infliximab (both autoimmune and inflammatory disorders, ‘AIID’) and rituximab (oncology and AIID) accounted for 80% of revenues in 2006. In 2007, eight of the 20 best-selling biotechnology drugs in the U.S. are therapeutic monoclonal antibodies. This rapid growth in demand for monoclonal antibody production has been well accommodated by the industrialization of mAb manufacturing.

結核病

結核病

色素沉着絨毛結節性滑膜炎

色素沉着絨毛結節性滑膜炎

色素沉着絨毛結節性滑膜炎

Signs and symptoms

In general, pigmented villonodular synovitis often manifests initially as sudden onset, unexplained joint swelling and pain; the joint swelling is disproportionate to the amount of pain the patient feels at first. Decreased motion and increased pain occur as the disease state progresses as well as locking of the joint. The localized form often manifests initially as a painless, slow-growing mass and progresses to the other common symptoms of PVNS. The swelling often feels warm to the touch. Diffuse PVNS symptoms are often confused with those of rheumatoid arthritis. While pigmented villonodular synovitis can occur in both pediatric and geriatric patients, it is more common with ages 20–50.

Complications

PVNS is locally aggressive and can spread to surrounding tissues, causing bone erosion and tissue damage. If not treated early, it can spread to areas outside the joint, extra-articular, and potentially cause permanent loss of range as well as intense pain. The disorder also has, on average, a 45% rate of recurrence.

Causes

The exact cause is unknown. Some doctors believe it is caused by abnormal metabolism of fat. Others think it may be caused by repetitive inflammation. Some feel that blood within the joint may cause the inflammatory change. Risk factors for PVNS developing are not yet understood. However, a common theme is a trauma experienced to the joint prior to the onset of symptoms.

Diagnosis

Micrograph of PVNS showing pigmented hemosiderin-laden macrophages (brown/red). H&E stain.

PVNS is radiologically diagnosed by magnetic resonance imaging (MRI). The disorder is difficult to identify and is often not diagnosed for four years or more after presentation due to nonspecific symptoms or a general paucity of symptoms.

Classification

Pigmented villonodular synovitis, described distinctly in 1941 by Charles J. Sutro, L. Lichtenstein, and H.L. Jafe, comes in two forms: localized and diffuse. Diffuse PVNS affects the entire synovium and typically occurs in large joints such as the knee or hip. Localized, or nodular, PVNS is less common than the diffuse form and typically occurs in smaller joints such as the hands and feet. Localized PVNS often arises in the form of a large benign tumour on the tendon sheaths of the joint. As the tumor grows in the joint, it damages the surrounding bone and tissues. Localized PVNS is predominantly found in females and is frequently found in the fingers. Although rare, localized PVNS may develop in large joints. In either case, the knee is the most commonly affected joint (80% of cases), followed by the hip, and less commonly the ankles and shoulders. PVNS is generally found more in men than women. 2 cases per million population; incidence of the localized form is 9 cases per million.

Pathology

The synovial fluid of the joint is often grossly hemorrhagic.

PVNS, under the microscope, looks as the name of the condition suggests; it is composed of nodules and/or villi and has an abundant number of (pigmented) hemosiderin-laden macrophages.

Treatment

Once PVNS is confirmed by biopsy of the synovium of an affected joint, an arthroscopic or open synovectomy of the affected area is the most common treatment. Bone lesions caused by the disorder are removed and bone grafting is performed as needed. Because diffuse PVNS has a relatively high rate of recurrence, radiation therapy or chemotherapy may be considered as a treatment option. In some cases, a total joint replacement is needed to relieve symptoms when PVNS causes significant joint destruction.

費爾蒂症候群

費爾蒂症候群

費爾蒂症候群

Signs and symptoms

The symptoms of Felty's syndrome are similar to those of rheumatoid arthritis. Patients suffer from painful, stiff, and swollen joints, most commonly in the joints of the hands, feet, and arms. In some affected individuals, Felty's syndrome may develop during a period when the symptoms and physical findings associated with rheumatoid arthritis have subsided or are not present; in this case, Felty's syndrome may remain undiagnosed. In more rare instances, the development of Felty's syndrome may precede the development of the symptoms and physical findings associated with rheumatoid arthritis.

Felty's syndrome is also characterized by an abnormally enlarged spleen (splenomegaly) and abnormally low levels of certain white blood cells (neutropenia). As a result of neutropenia, affected individuals are increasingly susceptible to certain infections. Keratoconjunctivitis sicca may occur due to secondary Sjögren's syndrome. Individuals with Felty's syndrome may also experience fever, weight loss, and/or fatigue. In some cases, affected individuals may have discoloration (abnormal brown pigmentation) of the skin, particularly of the leg, sores (ulcers) on the lower leg, and/or an abnormally large liver (hepatomegaly). In addition, affected individuals may have abnormally low levels of circulating red blood cells (anemia), a decrease in circulating blood platelets that assist in blood clotting functions (thrombocytopenia), abnormal liver function tests and/or inflammation of the blood vessels (vasculitis).

Complications

• Recurrent infection
• Enlargement of the spleen causing too few red blood cells and platelets in the bloodstream
• Enlarged lymph nodes
• Skin hyperpigmentation
• Cutaneous ulceration

Causes

The cause of Felty's syndrome is unknown, but it has been found to be more common in those with chronic rheumatoid arthritis. Some patients share the HLA-DR4 serotype. This syndrome is mostly present in people having extra articular manifestations of rheumatoid arthritis. People with this syndrome are at risk of infection because they have a low white blood cell count.

Mechanism

The underlying pathogenesis of Felty's syndrome is not clear.

Rheumatoid Arthritis

A 65 year old patient with rheumatoid arthritis displaying swan neck deformity.

Rheumatoid arthritis is an autoimmune disease that is characterized by inflammation of the synovial joints due to attack by the body's own immune system. In this condition, the white blood cells travel through the blood stream to the synovial joints and release pro-inflammatory cytokines upon arrival. The result of this chemical release causes the synovial cells to release harmful chemicals in response as well as begin the growth of new blood vessels, forming a pannus. The pannus receives blood supply from the newly formed vessels and grows inward, invading the articular cartilage and bone within the joint. The damage to the once healthy tissue causes inflammation and ultimately fluid build-up in the joint. An accumulation of fluid results and the joints swell, slowly decreasing the space that keeps the bones from touching. If this condition is not treated, the joint space will completely narrow, causing ankylosis. At the advanced stage of ankylosis, joint mobility is completely occluded. Early presentation is commonly seen in the joints of hands and of the feet. As the disease progresses it can be seen in the knees, wrists, hips, and shoulders. This condition can affect and damage several other body systems such as the eyes, heart, lungs, and blood vessels.

Rheumatoid arthritis is a condition that cannot be cured but symptoms can be treated using certain medications alone or in conjunction. Due to the increased inflammatory response of the body's immune system, this condition can cause a reduction in red and white blood cells.

Neutropenia

In Felty's syndrome, chronic activation of neutrophils progresses to neutropenia and unabated infections. Neutropenia is a decreased concentration of neutrophils in the blood. Neutrophils are the most abundant cells among white blood cells and play an important role in the immune system by destroying bacteria via phagocytosis. Inflammatory chemicals draw neutrophils to the area where they congregate and fight infection. A decrease in the number of neutrophils stimulates an autoimmune response which leads to arthritis. The loss and destruction of neutrophils leading to neutropenia is therefore, inflammation-driven due to the body's need for the immune response.

Splenomegaly

Splenomegaly is a condition of the spleen causing it to be enlarged. The splenic condition involving Felty syndrome is more specifically noted as inflammatory splenomegaly. The spleen is an important lymphatic organ that is involved in filtration of the blood by discarding old and damaged red blood cells as well as maintaining platelet levels. The spleen is a lymphatic organ, which means it is largely involved in the immune system and immune responses. When the spleen becomes enlarged, it is a strong sign of infection somewhere in the body, and can be caused by inflammatory conditions such as rheumatoid arthritis. The increased need for production assistance of white blood cells to affected areas causes hyperfunction of the spleen. This increase in defense activities ultimately causes hypertrophy of the spleen, leading to splenomegaly. The spleen is found in the left upper quadrant (LUQ) of the peritoneal cavity and due to its enlargement, can cause stress on neighboring organs.

Diagnosis

This condition affects less than 1% of patients with rheumatoid arthritis. The presence of three conditions: rheumatoid arthritis, an enlarged spleen (splenomegaly), and an abnormally low white blood cell count are indications that Felty's syndrome is possibly occurring. This condition as a whole is difficult to diagnose due to its complexity given a combination of disorders. It is commonly overlooked or misdiagnosed as other conditions (e.g., leukemia, systemic lupus erythrematosus) because of the rarity and lack of good understanding about it. An acronym can be used to make recognizing this disease somewhat easier:

S: Splenomegaly

A: Anemia

N: Neutropenia

T: Thrombocytopenia

A: Arthritis (rheumatoid)

Conditions of the Blood

A complete blood count (CBC) can be done to diagnose anemia (normochromic, normocytic), thrombocytopenia, and neutropenia. Abnormal liver function tests are commonly used to help in diagnosis as the spleen and liver are strongly affected by one another.

Splenomegaly

If rheumatoid arthritis is present and other symptoms occur that are not commonly found within RA itself, such as a palpable spleen, further testing should be done. A palpable spleen is not always a clinical significance, therefore CT scan, MRI, or ultrasound can be administered in order to help diagnose the condition. According to Poulin et al, dimensional guidelines for diagnosing splenomegaly are as follows:

• Moderate if the largest dimension is 11–20 cm
• Severe if the largest dimension is greater than 20 cm

Rheumatoid Arthritis

RA in patients with Felty's syndrome is chronic (after 10–15 years), and presents with increased severity along with extra articular manifestations. RA can be mistaken for other conditions such as gout if not clinically diagnosed. Diagnosis can be confirmed by use of X-rays or synovial fluid analysis.

Treatment

There is no real treatment for Felty's syndrome, rather the best method in management of the disease is to control the underlying rheumatoid arthritis. Immunosuppressive therapy for RA often improves granulocytopenia and splenomegaly; this finding reflects the fact that Felty's syndrome is an immune-mediated disease. A major challenge in treating FS is recurring infection caused by neutropenia. Therefore, in order to decide upon and begin treatment, the cause and relationship of neutropenia with the overall condition must be well understood. Most of the traditional medications used to treat RA have been used in the treatment of Felty's syndrome. No well-conducted, randomized, controlled trials support the use of any single agent. Most reports on treatment regimens involve small numbers of patients.

Splenectomy may improve neutropenia in severe disease.

Use of rituximab and leflunomide have been proposed.

Use of gold therapy has also been described.

幼年特發性關節炎

幼年特發性關節炎

參考文獻

參考文獻