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

Arthritis Rheumatol. 2017 Aug;69(8):1576-1579. doi: 10.1002/art.40127. Epub 2017 Jun 26.

Abstract

Objective: To examine the prevalence of α1 -antitrypsin deficiency (AATD) in rheumatoid arthritis (RA), and to determine whether AATD is associated with higher levels of rheumatoid factor (RF), antinuclear antibodies (ANAs), and anti-citrullinated peptide autoantibodies (ACPAs).

Methods: RF, ANAs, and ACPAs were measured by standard immunoturbidimetry, immunofluorescence assay, and enzyme-linked immunosorbent assay, respectively. Characterization of AAT phenotypes was performed by isoelectric focusing and immunofixation. The chi-square test with Yates' correction and the Mann-Whitney U test were used to assess the prevalence of alleles associated with AATD in RA and to compare mean antibody titers, respectively.

Results: Of 246 patients with RA, 24 who were heterozygous for AATD were identified, with no statistically significant difference in the prevalence of AATD between RA patients and the general population (P = 0.39). A positive association between heterozygosity for AATD and the production of ACPAs was observed (P < 0.0001), with increased ACPA titers recorded in the AATD RA cohort compared with the general population (P = 0.01).

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antinuclear / immunology*
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / immunology
  • Case-Control Studies
  • Genotype
  • Humans
  • Mutation
  • Peptides, Cyclic / immunology*
  • Phenotype
  • Polymorphism, Genetic
  • Prevalence
  • Rheumatoid Factor / immunology*
  • alpha 1-Antitrypsin / genetics*
  • alpha 1-Antitrypsin Deficiency / epidemiology
  • alpha 1-Antitrypsin Deficiency / genetics*

Substances

  • Antibodies, Antinuclear
  • Autoantibodies
  • Peptides, Cyclic
  • alpha 1-Antitrypsin
  • cyclic citrullinated peptide
  • Rheumatoid Factor