THE DIAGNOSTIC AND CLINICAL VALUE OF DETERMINATION OF α1-ANTITRYPSIN PHENOTYPE IN SYSTEMIC VASCULITIDES

Abstract

α1-Antitrypsin (α1-AT) deficiency is a common genetic disorder characterized by low serum α1-AT levels and a clinical manifestation of pulmonary emphysema and liver disease. In addition to its classical manifestations, α1-AT deficiency frequently accompanies granulomatosis with polyangiitis (GPA); in this case the role of α1-AT deficiency in the clinical course of GPA has not been defined. Objective: to estimate the prevalence of pathological α1-AT phenotypes in GPA and other systemic vasculitides (SV) and to determinate their impact on the clinical course of GPA. Subjects and methods. The investigation enrolled 86 patients with SV, including GPA (n=47), microscopic polyangiitis (MPA) (n=16), eosinophilic granulomatosis with polyangiitis (EGPA) (n=12), and polyarteritis nodosa (PAN) (n=11). A control group included 46 healthy donors. Isoelectric focusing was used to phenotype α1-AT in blood samples and its concentrations were determined. The phenotypes of α1-AT were compared with the overall SV activity index using the Birmingham Vasculitis Activity Score (BVAS), the vasculitis damage index (VDI), the nature of an organ lesion, and the markers of immune inflammation (proteinase 3-antineutrophil cytoplasmic antibodies, total IgG, and C3 and C4 fractions of the complement system). Results and discussion. Pathological α1-AT phenotypes were detected in 17% (8/47) of the patients with GPA, 6.25% (1/16) of those with MPA and absent in EGPA and PAN. Patients with GPA had PiZZ (n=1), PiMZ (n=4), PiMF (n=2), and PiMS (n=1) phenotypes; those with MPA had a PiMS-phenotype. The detection of a pathological α1-AT phenotype in patients with GPA was characterized by the high values of BVAS and VDI (p<0.05) and the elevated levels of serum creatinine (p><0.01), anti-proteinase 3 antibodies, IgG, C3 and C4 fractions of the complement system (p><0.05). Conclusion. Pathological α1-AT phenotypes are more frequently detected in patients with GPA, which is accompanied by an enhanced immunological activity of the disease and high activity and damage indices. Key words: α1-antitrypsin; α1-antitrypsin deficiency; phenotyping; granulomatosis with polyangiitis; systemic vasculitis.><0.05) and the elevated levels of serum creatinine (p<0.01), anti-proteinase 3 antibodies, IgG, C3 and C4 fractions of the complement system (p<0.05). Conclusion. Pathological α1-AT phenotypes are more frequently detected in patients with GPA, which is accompanied by an enhanced immunological activity of the disease and high activity and damage indices.

Keywords

• α1-antitrypsin
• α1-antitrypsin deficiency
• phenotyping
• granulomatosis with polyangiitis
• systemic vasculitis