Clinical Effect of Alpha-1 Antitrypsin Deficiency in Antineutrophil Cytoplasmic Antibody–associated Vasculitis: Results from a French Retrospective Monocentric Cohort

Objective Deficiency in alpha-1-antitrypsin (AAT) is a possible pathogenic cofactor in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the clinical impact of AAT deficiency remains poorly established in this setting. This study aimed to describe the clinical phenotypes and outcomes of AAV according to AAT phenotypes. Methods This study was conducted retrospectively at Caen University Hospital and included all consecutive granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with positive proteinase 3-ANCA or myeloperoxidase-ANCA, from January 2000 or September 2011, respectively, to June 2016. AAT dosage (nephelometry) and phenotyping (isoelectric focusing in agarose gel) were performed. Results Among the 142 AAV patients, including 88 GPA and 54 MPA, 102 (72%) had the MM phenotype, 5 (4%) had a non-polymerogenic M-variant phenotype, 18 (13%) had MZ, 12 (8%) had MS, 2 (1%) had ZZ, 2 (1%) had SZ and 1 (1%) had SS. M, Z and S allele frequencies were 84, 8 and 6%, respectively. No association was observed between AAT deficiency and ANCA subtype or AAV phenotype, except for intra-alveolar haemorrhage, which was more frequent in patients harbouring at least one of the deficient Z or S alleles than in those without any deficient alleles (p Conclusion This study shows that AAT deficiency confers, independently of ANCA subtype, a higher risk of intra-alveolar haemorrhage. Prospective studies are required to refine these data and to assess the need for replacement therapy in AAT-deficient AAV patients.