The Diagnostic Value of alpha-1-antitrypsin Phenotype in Patients with Granulomatosis with Polyangiitis (Wegener's Granulomatosis)

Аннотация

Background: Deficiency of alpha-1 protease inhibitor, or alpha-1-antitrypsin (A1AT), predisposes to chronic lung diseases and some extra-pulmonary pathology. Besides classical implications, such as pulmonary emphysema and other associated lung diseases, A1AD is also known to be associated with granulomatosis with polyangiitis (GPA, or Wegener’s).

Objectives: The aim of our study was to evaluate the frequency of mutated A1AT forms and its clinical significance among GPA patients.

Methods: We analysed 38 samples of sera, collected from GPA patients. Detailed clinical data, including Birmingham Vasculitis Activity Score (BVAS), incidence of lung involvement, anti-(Pr3) antibodies concentrations and other laboratory data were collected. We also studied control group of 46 healthy donors. All collected samples underwent A1AT phenotyping by isoelectrofocusing (IEF) and turbidimetric A1AT measurement.

Results: Mutated A1AT variants were revealed in 18.4% (7/38) cases and included following phenotypes: 1ZZ, 4MZ and 2MF. The mean A1AT concentration in samples with pathological genetic A1AT forms was significantly lower (P=0,0038), than in normal A1AT phenotype. According to reference values, only 2 of 7 pathological samples demonstrated decreased A1AT concentration. Comparing BVAS activity, we found that patients with mutated A1AT phenotype had significantly higher vasculitis activity, as well as anti-PR3 antibodies concentration. When analysis of nonspecific systemic inflammation markers was performed, the significant difference (P<0.05) was found only between means of erythrocyte sedimentation rate (ESR).

Conclusions: Laboratory testing to find pathological A1AT forms are not usually ordered for patients with systemic vasculitides. During medical examination of GPA patients the possibility of A1AT deficiency should be considered and may be verificated by IEF.