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HLA-B*08 identified as the most prominently associated major histocompatibility complex locus for anti-carbamylated protein antibody-positive/anti-cyclic citrullinated peptide-negative rheumatoid arthritis

Abstract: Objective: Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti-carbamylated protein antibody-positive (anti-CarP+) RA. Methods: Analyses were restricted to RA patients who were anti-cyclic citrullinated peptide antibody negative (anti-CCP-), because the anti-CCP status dominated the results otherwise. Therefore, we studied samples from 1,821 anti-CCP- RA patients and 6,821 population controls from Spain, Sweden, and the Netherlands. The genotypes for ~8,000 MHC biallelic variants were assessed by dense genotyping and imputation. Their association with the anti-CarP status in RA patients was tested with logistic regression and combined with inverse-variance meta-analysis. Significance of the associations was assessed according to a study-specific threshold of P < 2.0 × 10-5 . Results: The HLA-B*08 allele and its correlated amino acid variant Asp-9 showed a significant association with anti-CarP+/anti-CCP- RA (P < 3.78 × 10-7 ; I2 = 0). This association was specific when assessed relative to 3 comparator groups: population controls, anti-CarP-/anti-CCP- RA patients, and anti-CCP- RA patients who were positive for other anti-citrullinated protein antibodies. Based on these findings, anti-CarP+/anti-CCP- RA patients could be separated from other antibody-defined subsets of RA patients in whom an association with the HLA-B*08 allele has been previously demonstrated. No other MHC variant remained associated with anti-CarP+/anti-CCP- RA after accounting for the presence of the HLA-B*08 allele. Specifically, the reported association of HLA-DRB1*03 was observed at a level comparable to that reported previously, but it was attributable to linkage disequilibrium. Conclusion: These results identify HLA-B*08 carrying Asp-9 as the MHC locus showing the strongest association with anti-CarP+/anti-CCP- RA. This knowledge may help clarify the role of the HLA in susceptibility to specific subsets of RA, by shaping the spectrum of RA autoantibodies.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Congreso: ACR Convergence (2021)

 Fuente: Arthritis and Rheumatology, 2021, 73(6), 963-969

Editorial: John Wiley and Sons Ltd

 Año de publicación: 2021

Nº de páginas: 7

Tipo de publicación: Artículo de Revista

 DOI: 10.1002/art.41630

ISSN: 2326-5205,2326-5191

Url de la publicación: https://www.doi.org/10.1002/art.41630

Autoría

REGUEIRO, CRISTINA

CASARES-MARFIL, DESIRE

LUNDBERG, KARIN

KNEVEL, RACHEL

ACOSTA-HERRERA, MARIALBERT

RODRIGUEZ-RODRIGUEZ, LUIS

LOPEZ-MEJIAS, RAQUEL

PEREZ-PAMPIN, EVA

TRIGUERO-MARTINEZ, ANA

NUÑO, LAURA

FERRAZ-AMARO, IVAN

RODRIGUEZ-CARRIO, JAVIER

LOPEZ-PEDRERA, ROSARIO

ROBUSTILLO-VILLARINO, MONTSE

CASTAÑEDA, SANTOS

REMUZGO-MARTINEZ, SARA

ALPERI, MERCEDES

ALEGRE-SANCHO, JUAN J