Michalski J P, McCombs C C, Scopelitis E, Biundo J J, Medsger T A
Arthritis Rheum. 1986 May;29(5):586-91. doi: 10.1002/art.1780290502.
Alpha 1-antitrypsin is a glycoprotein that functions as the major protease inhibitor in human serum. Many genetic variants of alpha 1-antitrypsin can be detected by electrophoretic techniques. We used isoelectric focusing on ultrathin gels to determine the common M subtypes as well as other variants of alpha 1-antitrypsin in 62 white patients with rheumatoid arthritis (RA) and 51 white patients with systemic sclerosis (SSc). We found no increased prevalence of variant phenotypes in either disease group as a whole. In RA, however, the association between pulmonary interstitial fibrosis and alpha 1-antitrypsin variants was striking. Interstitial fibrosis was seen on chest roentgenogram in only 1 of 30 subjects apparently homozygous for M1 (the "wild type" or "normal" phenotype), compared with 13 of 32 patients with variant phenotypes. Seven of 15 patients with M1M2 (the most common variant phenotype) had pulmonary fibrosis. In contrast, there was no apparent association of variant phenotypes with pulmonary involvement in SSc. Our findings suggest a possible role of alpha 1-antitrypsin in the pathogenesis of interstitial fibrosis in patients with RA. The absence of such an association in SSc suggests that pulmonary involvement in these 2 rheumatic diseases may have different pathogeneses.
α1-抗胰蛋白酶是一种糖蛋白，在人血清中作为主要的蛋白酶抑制剂发挥作用。α1-抗胰蛋白酶的许多基因变体可通过电泳技术检测到。我们使用超薄凝胶等电聚焦法来确定62例类风湿关节炎（RA）白人患者和51例系统性硬化症（SSc）白人患者中α1-抗胰蛋白酶的常见M亚型以及其他变体。我们发现，在这两个疾病组中，变异表型的总体患病率均未增加。然而，在RA中，肺间质纤维化与α1-抗胰蛋白酶变体之间的关联十分显著。在30名显然为M1纯合子（“野生型”或“正常”表型）的受试者中，只有1人胸部X线片显示有间质纤维化，而在32例具有变异表型的患者中，有13人出现了间质纤维化。15例M1M2（最常见的变异表型）患者中有7例患有肺纤维化。相比之下，在SSc中，变异表型与肺部受累之间没有明显关联。我们的研究结果表明，α1-抗胰蛋白酶可能在RA患者间质纤维化的发病机制中起作用。SSc中不存在这种关联表明，这两种风湿性疾病的肺部受累可能具有不同的发病机制。
