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- Title
Association of Valine and Leucine at HLA-DRB1 Position 11 With Radiographic Progression in Rheumatoid Arthritis, Independent of the Shared Epitope Alleles but Not Independent of Anti-Citrullinated Protein Antibodies.
- Authors
Steenbergen, H. W.; Raychaudhuri, S.; Rodríguez‐Rodríguez, L.; Rantapää‐Dahlqvist, S.; Berglin, E.; Toes, R. E. M.; Huizinga, T. W. J.; Fernández‐Gutiérrez, B.; Gregersen, P. K.; Helm‐van Mil, A. H. M.
- Abstract
Objective For decades it has been known that the HLA-DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide-binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe at HLA-DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti-citrullinated protein antibody (ACPA) status. Methods A total of 4,911 radiograph sets from 1,878 RA patients included in the Leiden Early Arthritis Clinic (The Netherlands), Umeå (Sweden), Hospital Clinico San Carlos-Rheumatoid Arthritis (Spain), and National Data Bank for Rheumatic Diseases (US) cohorts were studied. HLA was imputed using single-nucleotide polymorphism data from an Immunochip, and the amino acids listed above were tested in relation to radiographic progression per cohort using an additive model. Results from the 4 cohorts were combined in inverse-variance weighted meta-analyses using a fixed-effects model. Analyses were conditioned on SE and ACPA status. Results Val and Leu at HLA-DRB1 position 11 were associated with more radiographic progression (meta-analysis P = 5.11 × 10−7); this effect was independent of SE status (meta-analysis P = 0.022) but not independent of ACPA status. Phe at HLA-DPB1 position 9 was associated with more severe radiographic progression (meta-analysis P = 0.024), though not independent of SE status. Asp at HLA-B position 9 was not associated with radiographic progression. Conclusion Val and Leu at HLA-DRB1 position 11 conferred a risk of a higher rate of radiographic progression independent of SE status but not independent of ACPA status. These findings support the relevance of these amino acids at position 11.
- Subjects
ACADEMIC medical centers; CONFIDENCE intervals; LEUCINE; MEDICAL cooperation; RESEARCH; RESEARCH funding; RHEUMATOID arthritis; VALINE; WORLD health; HLA-B27 antigen; DATA analysis software; GENOTYPES
- Publication
Arthritis & Rheumatology, 2015, Vol 67, Issue 4, p877
- ISSN
2326-5191
- Publication type
Article
- DOI
10.1002/art.39018