Brief Report: Genetic Variation of the α₁‐Antitrypsin Gene Is Associated With Increased Autoantibody Production in Rheumatoid Arthritis

Abstract

AAT heterozygous status in RA is strongly associated with positive ACPAs and may define a distinct subset of patients with increased disease severity.

Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies

“…Genetic variation of α1-antitrypsin has been found to be related to ACPA production in RA. 21 However, whether the production is directly linked to α1-antitrypsin deficiency per se or results from altered autophagy induced by the mutant α1-antitrypsin Z requires further study. The increased response of type I interferon gene associated with Th2 cell induction and B cell proliferation correlates with ACPA production.…”

Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in rheumatoid arthritis

“…Furthermore dimer S100A8/A9 has been reported as good predictive biomarker to etanercept in RA [10]. Haptoglobin, α-1 antitrypsin, C-reactive protein (CRP) and prealbumin which are involved in inflammatory processes and/or described in RA [11][12][13][14] may represent potential predictive biomarkers.…”

Could Autophagy Induced by Misfolded Mutant α1‐Antitrypsin Z in Synovitis Explain the Association of α1‐Antitrypsin Z With Increased Anti–Citrullinated Protein Antibody Production in Rheumatoid Arthritis? Comment on the Article by McCarthy et al

“…We suggest that individuals with AATZ who develop synovitis are at an increased risk of ACPA generation as a consequence of increased macrophage AATZ generation, which results in autophagy leading to intracellular peptide citrullination and subsequent ACPA generation. This would explain the observations of McCarthy et al that AATZ was not overrepresented in their RA cohort compared to controls, but in the context of RA disease associated with ACPA generation .…”

“…We read with interest the article “Genetic variation of the α 1 ‐antitrypsin gene is associated with increased autoantibody production in rheumatoid arthritis” by McCarthy et al . A strong association between mutant α 1 ‐antitrypsin Z (AATZ) and anti–citrullinated protein antibody (ACPA) production was noted in rheumatoid arthritis (RA).…”