In:
Arthritis & Rheumatology, Wiley, Vol. 71, No. 3 ( 2019-03), p. 331-339
Abstract:
Recognition of a new type of rheumatoid arthritis ( RA )–specific autoantibody, the anti–carbamylated protein antibodies (anti‐CarP), has provided an opportunity to improve the management and understanding of RA . The current study was undertaken to assess the relationship between anti‐CarP antibodies and HLA – DRB 1 alleles in RA . Methods Serum samples were obtained from 3 different collections, comprising a total of 1,126 RA patients. Serum reactivity against in vitro carbamylated fetal calf serum proteins was determined by enzyme‐linked immunosorbent assay. HLA – DRB 1 alleles were determined using either hybridization techniques or imputation from HLA ‐dense genotypes. Results of these analyses were combined in a meta‐analysis with data from 3 previously reported cohorts. The carrier frequencies of the common HLA – DRB 1 alleles were compared between the antibody‐positive RA subgroups and the double‐negative subgroup of RA patients stratified by anti–citrullinated protein antibody ( ACPA )/anti‐CarP antibody status, and also between the 4 RA patient strata and healthy controls. Results Meta‐analysis was conducted with 3,709 RA patients and 2,305 healthy control subjects. Results revealed a significant increase in frequency of HLA – DRB 1*03 carriers in the ACPA −/anti‐CarP+ subgroup as compared to ACPA −/anti‐CarP− RA patients and healthy controls; this was consistently found across the 6 sample collections. This association of HLA – DRB 1*03 with ACPA −/anti‐CarP+ RA was independent of the presence of the shared allele ( SE ) and any other confounders analyzed. No other allele was specifically associated with the ACPA −/anti‐CarP+ RA patient subgroup. In contrast, frequency of the SE was significantly increased in the ACPA +/anti‐CarP− and ACPA +/anti‐CarP+ RA patient subgroups, without a significant distinction between them. Furthermore, some alleles (including HLA – DRB 1*03 ) were associated with protection from ACPA + RA . Conclusion These findings indicate a specific association of HLA – DRB 1*03 with ACPA −/anti‐CarP+ RA , suggesting that preferential presentation of carbamylated peptides could be a new mechanism underlying the contribution of HLA alleles to RA susceptibility.
Type of Medium:
Online Resource
ISSN:
2326-5191
,
2326-5205
DOI:
10.1002/art.2019.71.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2754614-7
