CLINICAL CHARACTERISTICS OF PATIENTS WITH ANCA-ASSOCIATED VASCULITIS WITH AND WITHOUT ALPHA-1 ANTITRYPSIN DEFICIENCY ALLELES
Authors: Lynn Fussner et al.
Alpha-1 antitrypsin (A1AT) – which is readily detectable in protein electrophoresis – serves as the predominant endogenous inhibitor of proteinase 3 (PR3). It is conceivable that functional or quantitative changes of A1AT may have an impact on ANCA-associated vasculitis (AAV). In line with this hypothesis, two large genome-wide association studies found that mutations in SERPINA1, the gene encoding A1AT, are associated with increased risk of developing AAV.
This report describes the clinical characteristics of a large cohort of patients with AAV with and without A1AT deficiency alleles. DNA was obtained from patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Demographics and clinical characteristics are described and compared between patients with and without A1AT deficiency alleles. Genotype data from 2145 unique patients with GPA and MPA were identified and analyzed.
340 patients (15.9%) had at least one A1AT deficiency allele. Mean age at AAV diagnosis and sex were similar among patients with and without A1AT deficiency alleles. Patients with deficiency had more often a clinical phenotype of GPA (90.3% with deficiency alleles vs. 83.5% MM, p=0.003), and were more frequently PR3-ANCA positive (74.5% with deficiency alleles vs. 63.3% MM, p< 0.001). Patients with deficiency alleles were more likely overall to have granulomatous manifestations of AAV (88.1% with deficiency alleles vs. 80.1% MM, p=0.024), while there was no difference in the frequency of capillaritis manifestations (74.8% with deficiency alleles vs. 77.8% MM, p=0.430).
Although the presented data do not have a direct clinical impact, it is interesting to learn that the well-known alpha-1 antitrypsin may play a role in pathogenetic events in GPA and granuloma formation. The field of alpha-1 Antitrypsin expression and function is rapidly evolving. It is conceivable that this protein might once play a therapeutic role.