参考文献1Moore PA,Belvedere O,Orr A,et al.BLyS:member of the tumor necro-sis factor fa mily and B l ymphoc yte s timulator.Science,1999,285(5425): 260-263.2Schneider P,Mac Kay F,Steiner V,et al.BAFF,a novel ligand of the tumor necros is factor fa mily,sti mul ates B cell growth.J Exp M ed,1999, 189(11):1747-1756.3Shu HB,Hu WH,Johns on H.TALL-1is a novel member of the TNF fa mily that is down-regulated by mitogens.J Leukoc Biol,1999,65(5): 680-683.4Mukhopadhyay A,Ni J,Zhai Y,et al.Identification and characterization of a novel cytokine,THANK,a TNF homologue that acti vates apopt os is, nuclear factor-kappaB,and c-J un N H2-terminal kinase.J Biol Chem, 1999,274(23):15978-15981.5Nardelli B,Belvedere O,Roschke V,et al.Synthes is and rel eas e of B-l ymphocyte sti mulator fro m myeloid cells.Blood,2001,97(1):198-204.6Gross JA,J ohns ton J,Mudri S,et al.TACI and BCM A are receptors fora TNF homol ogue implicated in B-cell autoimmune disease.Nat ure,2000,404(6781):995-999.7Thomps on J S,Bixl er SA,Qian F,et al.BA FF-R,a newly identified TNF receptor that specificall y interacts with BAFF.Science,2001,293 (5537):2108-2111.8Wang H,M arsters SA,Baker T,et al.TACI-ligand interacti ons are re-quired for T cell activation and coll agen-induced arthritis in mice.Nat Im-munol,2001,2(7):632-637.9Mackay F,Woodcock SA,Lawt on P,et al.Mice transgenic for BAFF de-vel op l ymphoc ytic disorders along with autoi mmune manifestations.J Exp Med,1999,190(11):1697-1710.10Khare SD,Sarosi I,Xia XZ,et al.Severe B cell hyperplas ia and autoim-mune dis eas e in TALL-1transgenic mice.Proc Natl Acad Sci U S A,2000,97(7):3370-3375.11Yu G,Boone T,Del aney J,et al.APR IL and TALL-I and receptors BC-MA and TACI:s yste m for regulating humoral i mmunity.Nat Immunol, 2000,1(3):252-256.12Stohl W.Sys temic l upus erythematos us:a blissl es s disease of too much BLyS(B lymphoc yte s timulator)protein.Curr Opin R heumatol,2002,14(5):522-528.13Yan M,Brady JR,Chan B,et al.Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain wit h severe B cell deficiency.Curr Biol,2001,11(19):1547-1552.14Yan M,Wang H,Chan B,et al.Activation and accumulation of B cells in TACI-deficient mice.Nat Immunol,2001,2(7):638-643.15Schie mann B,Gommerman JL,Vora K,et al.An es sential role for BAFF in t he normal development of B cells through a BCMA-independent path-way.Science,2001,293(5537):2111-2114.16Llorente L,R ichaud-Patin Y,Wijdenes J,et al.Spontaneous production of interleukin-10by B lymphocytes and monocytes in s ystemic lupus ery-the matosus.Eur Cytokine Net w,1993,4(6):421-427.17Viallard J F,Pellegrin JL,R anchin V,et al.Th1(IL-2,interferon-gamma(IFN-gamma))and Th2(IL-10,IL-4)c ytokine production by peripheral blood mononuclear cells(PBMC)from patients with s ystemic lu-pus erythe matosus(SLE).Clin Exp Immunol,1999,115(1):189-195. 18Hagi wara E,Gourley MF,Lee S,et al.Disease s everity in patients with systemic l upus erythematosus correlates with an increas ed ratio of inter-leukin-10:interferon-gamma-secreting cells in the peripheral blood.Arthritis Rheum,1996,39(3):379-385.19Miret C,Font J,Molina R,et al.R el ations hip of oncogenes(s Fas,Bcl -2)and c ytokines(IL-10,alfa-TNF)with the activit y of systemic lu-pus erythematos us.Anticancer Res,2001,21(4B):3053-3059.20Gescuk BD,Davis JC Jr.Novel therapeutic agents for s ystemic lupus ery-the matosus.Curr Opin Rheumatol,2002,14(5):515-521.(收稿日期:2002-11-12)·综述·皮肌炎和多发性肌炎的病因和发病机制的研究进展赵肖庆郑捷摘要皮肌炎和多发性肌炎的发病有一定的遗传倾向,但在不同的人群中并不相同。
感染可能会引起皮肌炎和多发性肌炎的发病。
肿瘤与皮肌炎和多发性肌炎相关。
皮肌炎的原发损害可能在毛细血管,多发性肌炎主要是由肌肉内浸润的细胞毒性T细胞杀伤肌细胞。
目前认为这个杀伤机制主要是通过穿孔素和颗粒酶。
主要组织相容性复合体Ⅰ类分子表达异常对于肌炎的发生有重要作用。
关键词皮肌炎多发性肌炎病因皮肌炎(DM)和多发性肌炎(P M)都属于特发性炎症性肌病(IIM),其共同特点是病因不明的慢性肌肉炎症以及由此而产生的肌无力症状,DM还作者单位:200025上海第二医科大学附属瑞金医院皮肤科本文主要缩写:D M:皮肌炎,PM:多发性肌炎,IIM:特发性炎症性肌病,HLA:人类白细胞抗原,TN Fα:肿瘤坏死因子α,MHC主要组织相容性复合体有其特征性的皮肤损害。
与大多数自身免疫性疾病一样,DM与PM的发病是具有遗传易感性的个体在环境因素的作用下引起的。
近来组化技术、遗传学方法和免疫学技术的发展促进了对DM和PM发病机制的了解。
一、病因(一)遗传因素:1.人类白细胞抗原(HL A)表型与II M的关联: Rider等[1]报道HLA-DRB1＊0301、与之连锁的DQA1＊0501以及第一个超变区有9EYSTS13序列的DRB1与白种人的II M有关联。
在韩国人的II M患者中,尽管其临床特征、自身抗体均与白人一致,但并不能发现与疾病关联的HLA-DRB1或DQA1位点;相反,在缺乏肌炎特异性抗体的韩国患者中,DRB1＊14是一个保护性因子。
在白人中未能发现Gm表型与II M有关联,但在韩国人中,Gm21是一个保护性因子。
Ichika wa等[2]报道了在日本人中DM和P M与HLA单倍型的关联。
在DM患者中HLA-DRB1＊1302 -DQA1＊0102-DQB1＊0604单倍型的出现频率(42.1%)明显高于正常对照(17.7%)和P M患者(9.4%)。
并且P M伴肺间质损害的患者中的HL A-DRB1＊0405-DQA1＊03-DQB1＊0401单倍型的出现频率(50.0%)明显高于正常对照(17.7%)和PM不伴肺间质损害的患者(5.5%)。