Alpha1‐antitrypsin phenotypes, including M subtypes, in pulmonary disease associated with rheumatoid arthritis and systemic sclerosis

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Abstract
Alpha1-antitrypsin is a glycoprotein that functions as the major protease inhibitor in human serum. Many genetic variants of α1-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 α-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 α1-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 α1-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.