title: The Diagnostic Value of Alpha-1-Antitrypsin Phenotype in Patients with Granulomatosis with Polyangiitis.
abstract: The deficiency of alpha-1 protease inhibitor, or alpha-1-antitrypsin (A1AT), predisposes to chronic lung diseases and extrapulmonary pathology. Besides classical manifestations, such as pulmonary emphysema and liver disease, alpha-1-antitrypsin deficiency (A1ATD) is also known to be associated with granulomatosis with polyangiitis (GPA or Wegener's granulomatosis). The aim of our study was to evaluate the frequency of allelic isoforms of A1AT and their clinical significance among GPA patients. Detailed clinical information, including Birmingham Vasculitis Activity Score (BVAS), incidence of lung involvement, anti-proteinase 3 (PR3) antibodies concentrations, and other laboratory data were collected in 38 GPA patients. We also studied serum samples obtained from 46 healthy donors. In all collected samples A1AT phenotyping by isoelectrofocusing (IEF) and turbidimetric A1AT measurement were performed. Abnormal A1AT variants were found in 18.4% (7/38) of cases: 1 ZZ, 4 MZ, 2 MF, and only 1 MZ in control group (2%). The mean A1AT concentration in samples with atypical A1AT phenotypes was significantly lower (P = 0.0038) than in normal A1AT phenotype. We found that patients with abnormal A1AT phenotypes had significantly higher vasculitis activity (BVAS) as well as anti-PR3 antibodies concentration. We conclude that A1AT deficiency should be considered in all patients with GPA.
authors.affiliation: First Pavlov State Medical University of St. Petersburg, Saint Petersburg 197022, Russia.
authors.forename: M Y
authors.identifier: 0000-0001-9630-257X
authors.initials: MY
authors.lastname: Pervakova
authors.affiliation: First Pavlov State Medical University of St. Petersburg, Saint Petersburg 197022, Russia.
authors.forename: V L
authors.identifier: 0000-0002-2079-0439
authors.initials: VL
authors.lastname: Emanuel
authors.affiliation: First Pavlov State Medical University of St. Petersburg, Saint Petersburg 197022, Russia.
authors.forename: O N
authors.identifier: 0000-0003-4678-3904
authors.initials: ON
authors.lastname: Titova
authors.affiliation: First Pavlov State Medical University of St. Petersburg, Saint Petersburg 197022, Russia.
authors.forename: S V
authors.identifier: 0000-0002-4998-3699
authors.initials: SV
authors.lastname: Lapin
authors.affiliation: North-Western Mechnikov State Medical University, Saint Petersburg 191015, Russia.
authors.forename: V I
authors.identifier: 0000-0001-8367-3144
authors.initials: VI
authors.lastname: Mazurov
authors.affiliation: North-Western Mechnikov State Medical University, Saint Petersburg 191015, Russia.
authors.forename: I B
authors.identifier: 0000-0002-7981-6349
authors.initials: IB
authors.lastname: Belyaeva
authors.affiliation: North-Western Mechnikov State Medical University, Saint Petersburg 191015, Russia.
authors.forename: A L
authors.identifier: 0000-0002-7675-5683
authors.initials: AL
authors.lastname: Chudinov
authors.affiliation: First Pavlov State Medical University of St. Petersburg, Saint Petersburg 197022, Russia.
authors.forename: T V
authors.identifier: 0000-0003-4896-3319
authors.initials: TV
authors.lastname: Blinova
authors.affiliation: First Pavlov State Medical University of St. Petersburg, Saint Petersburg 197022, Russia.
authors.forename: E A
authors.identifier: 0000-0001-5191-0221
authors.initials: EA
authors.lastname: Surkova