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Abstract
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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.
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