A majority of Brazilian patients with rheumatoid arthritis HLA-DRB1 alleles carry both the HLA-DRB1 shared epitope and anti-citrunillated peptide antibodies

Abstract

The objective of the present study was to evaluate the contribution of the shared epitope (SE), the rheumatoid arthritis (RA) protection model, and the occurrence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in RA patients from a genetically diverse population. One hundred and forty Brazilian RA patients and 161 matched controls were typed for HLA-DRB1 alleles using amplified DNA hybridized with sequence-specific oligonucleotide probes or primers. Patients were stratified according to the presence or absence of SE (DRB1*0401, *0404, *0405, *0101, *1001, and *1402), of the DERAA alleles (DRB1*0103, *0402, *1102, *1103, *1301, *1302, and *1304), and X (all other alleles). Anti-CCP antibodies were measured by ELISA. The combined frequency of SE-positive alleles was significantly greater (76.4 vs 23.6%, P < 0.0001) than the controls. The SE/SE and SE/X genotypes were over-represented (P < 0.0001, OR = 6.02) and DERAA/X was under-represented in RA patients (P < 0.001, OR = 0.49), whereas the frequencies of the SE/DERAA, X/X and X/DERAA genotypes were not significantly different from controls. The frequency of anti-CCP antibodies was higher in SE-positive patients than in SE-negative patients (64.6 vs 44.7%, P = 0.03; OR = 2.25). Although the Brazilian population is highly miscegenated, the results of this study support the findings observed in most genetically homogeneous populations with RA; however, they are not mutually exclusive but rather complementary. The participation of DRB1-DERAA alleles in protection against RA was also observed (OR = 0.4; 95%CI = 0.23-0.68).

Shared Epitope Alleles Remain A Risk Factor for Anti-Citrullinated Proteins Antibody (ACPA) – Positive Rheumatoid Arthritis in Three Asian Ethnic Groups

“…It was recently shown that HLA-DRB1 SE alleles are associated with increased levels of anti-citrullinated protein antibodies (ACPA) in Caucasian RA patients [15], [16], [17], [18]. It is unclear, however, whether this selective association between ACPA-positive RA and certain HLA-DRB1 alleles is valid in all ethnic groups, in particular in groups with distribution of HLA-DRB1 alleles different from those described in Caucasians.…”

A spectrum of susceptibility to rheumatoid arthritis within HLA-DRB1: stratification by autoantibody status in a large UK population

“…27 It has also been proposed that certain HLA-DRB1 alleles protect against development of RA, compared with other HLA-DRB1 non-SE alleles. Proposed protective motifs include: the 70 DERAA 74 sequence, [28][29][30][31] aspartic acid at position 70 (D 70 ), 32,33 , isoleucine at position 67 (I 67 ) 34 or S 1 ( 71 ERAA 74 (S 1E ) with 71 ARAA 74 (S 1A )). 18,20,35 S 3D ( 70 DRRAA 74 ) was 'neutral'.…”

Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese

“…One of the successful examples of replication is the association between HLA-DRB1 and susceptibility to RA that has been replicated repeatedly among Caucasian, Asian and other ethnic populations 10 11 12 . HLA-DRB1 is now considered as the strongest genetic factor for RA in most ethnic populations.…”