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Objective: Deficiency in alpha-1 antitrypsin (AAT) is a possible pathogenic cofactor in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the clinical effect 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 patients with AAV, including 88 GPA and 54 MPA, 102 (72%) had the MM phenotype, 5 (4%) had a nonpolymerogenic M-variant phenotype, 18 (13%) had the deficient allele 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 intraalveolar hemorrhage (IAH), which was more frequent in patients harboring at least 1 of the deficient Z or S alleles than in those without any deficient alleles (p < 0.01). Global, renal, or relapse-free survival rates were similar for all subgroups., Conclusion: This study shows that AAT deficiency confers, independently of ANCA subtype, a higher risk of IAH. Prospective studies are required to refine these data and to assess the need for replacement therapy in AAT-deficient patients with AAV.

Objectives: To describe the clinical-biological phenotype of ANCA-associated vasculitides (AAV) according to tobacco consumption., Methods: We conducted a descriptive study to describe that phenotype at diagnosis according to tobacco use. AAV patients entered in the French Vasculitis Study Group database with data on smoking habits were analysed. The clinical-biological phenotypes at diagnosis were compared according to current tobacco use (current smokers) or not (including previous and never smokers)., Results: AAV diagnoses were: granulomatosis with polyangiitis (GPA) for 583 (50%), eosinophilic granulomatosis with polyangiitis (EGPA) for 326 (28%) and microscopic polyangiitis (MPA) for 256 (22%). Among them, 973 patients (84%) never smoked, 116 (10%) were previous smokers and only 76 (6%) were current smokers. Current smokers were younger age (p=0.01), male gender (p=0.004), less frequently EGPA (p=0.017) and MPA (p=0.036), and had less frequent kidney involvement (p=0.10). Among GPA patients, current smokers, compared to non-current smokers, were younger age (p=0.02), male gender (p=0.08), more frequent skin involvement (p=0.03) and less frequent ENT involvement (p=0.06). Among EGPA patients, current smokers, compared to non-current smokers, were also younger (p=0.028) and had less frequent constitutional symptoms (p=0.02), arthralgias (p=0.04), renal involvement (p=0.025) and MPO-ANCA (p=0.02). Finally, analysis of MPA patients was impossible because only 6 (2%) were current smokers., Conclusions: These results suggest that tobacco use could differentially affect GPA and EGPA clinical-biological phenotypes, and support the role of environmental exposures in AAV development and its phenotype.