PT  - JOURNAL ARTICLE
AU  - Samuel Deshayes
AU  - Nicolas Martin Silva
AU  - Frédérique Grandhomme
AU  - Kathy Khoy
AU  - Delphine Mariotte
AU  - Jonathan Boutemy
AU  - Gwénola Maigné
AU  - Claire Brière-Bellier
AU  - Claire Delmas
AU  - Boris Bienvenu
AU  - Thierry Lobbedez
AU  - Hubert de Boysson
AU  - Achille Aouba
TI  - Clinical Effect of Alpha-1 Antitrypsin Deficiency in Antineutrophil Cytoplasmic Antibody–associated Vasculitis: Results from a French Retrospective Monocentric Cohort
AID  - 10.3899/jrheum.180591
DP  - 2019 Nov 01
TA  - The Journal of Rheumatology
PG  - 1502--1508
VI  - 46
IP  - 11
4099  - http://www.jrheum.org/content/46/11/1502.short
4100  - http://www.jrheum.org/content/46/11/1502.full
SO  - J Rheumatol2019 Nov 01; 46
AB  - 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.