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

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.

• Authors: Cormac McCarthy, Carl Orr, Laura T Fee, Tomás P Carroll, Danielle M Dunlea, David J L Hunt, Eimear Dunne, Paul O'Connell, Geraldine McCarthy, Dermot Kenny, Ursula Fearon, Douglas J Veale, Emer P Reeves, Noel G McElvaney
• Journal: Arthritis & rheumatology (Hoboken, N.J.) (Arthritis Rheumatol) Vol. 69 Issue 8 Pg. 1576-1579 (08 2017) ISSN: 2326-5205 [Electronic] United States
• PMID: 28409899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017, American College of Rheumatology.

Chemical References

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

Topics

• Antibodies, Antinuclear (immunology)
• Arthritis, Rheumatoid (epidemiology, genetics, 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, genetics)