Alpha 1-antitrypsin activity is markedly decreased in Wegener’s granulomatosis

Abstract: Abstract Alpha 1-antitrypsin (A1AT) is the most abundant proteinase inhibitor in plasma and the main inhibitor of Proteinase 3, the target antigen of antineutrophil cytoplasmic antibodies (ANCAs) that predominant in Wegeners’ granulomatosis. A1AT deficiency correlated with ANCA-associated vasculitis. This study explores the trypsin inhibitory capacity (TIC), specific activity, and phenotypic deficiency of A1AT in Wegener’s granulomatosis. Twenty-seven WG patients were studied. ANCA was tested by IIF and ELISA. Serum a1-anti-trypsin levels were quantified inWG patients and healthy controls by immunoturbidimetric assay. Serum TIC was assessed by the enzymatic colorimetric assay. Phenotypes of A1AT were detected by Isoelectric Focusing. A1AT concentration was equivalent in patients and controls; however, serum TIC (P = 0.001) and specific activity of A1AT (P = 0.001) were dramatically lower inWGpatients. Five patients had deficient phenotypes of A1AT: MZ (n = 3), MS (n = 1) and SS (n = 1). This was correlated with an increase in the prevalence of deficient phenotypes of A1AT in WG (P = 0.01). Trypsin inhibitory capacity and specific activity of A1AT were decreased inWGpatients and may be involve in disease pathogenesis and can worsen the clinical manifestations. This A1AT deficiency probably resulted from oxidative inactivation and/or enzymatic degradation of A1AT. This could result in localized deficiency of A1AT in vessel wall interfaces and lead to severe disease. Keywords Alpha 1-antitrypsin  Antineutrophil cytoplasmic antibody  Proteinase 3  Wegener’s granulomatosis