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. 2013 May 30;8(5):e64108.
doi: 10.1371/journal.pone.0064108. Print 2013.

HLA-DRB1 genotypes and the risk of developing anti citrullinated protein antibody (ACPA) positive rheumatoid arthritis

Nathalie Balandraud  1 , Christophe Picard, Denis Reviron, Cyril Landais, Eric Toussirot, Nathalie Lambert, Emmanuel Telle, Caroline Charpin, Daniel Wendling, Etienne Pardoux, Isabelle Auger, Jean Roudier
Affiliations

HLA-DRB1 genotypes and the risk of developing anti citrullinated protein antibody (ACPA) positive rheumatoid arthritis

Nathalie Balandraud et al. PLoS One. .

Abstract

Objective: To provide a table indicating the risk for developing anti citrullinated protein antibody (ACPA) positive rheumatoid arthritis (RA) according to one's HLA-DRB1 genotype.

Methods: We HLA-DRB1 genotyped 857 patients with ACPA positive RA and 2178 controls from South Eastern and Eastern France and calculated Odds Ratios (OR) for developing RA for 106 of 132 possible genotypes accounting for 97% of subjects.

Results: HLA-DRB1 genotypic ORs for developing ACPA positive RA range from 28 to 0.19. HLA-DRB1 genotypes with HLA-DRB1*04SE (HLA-DRB1*0404, HLA-DRB1*0405, HLA-DRB1*0408), HLA-DRB1*04∶01, HLA-DRB1*01 are usually associated with high risk for developing RA. The second HLA-DRB1 allele in genotype somewhat modulates shared epitope associated risk. We did not identify any absolutely protective allele. Neither the Reviron, nor the du Montcel models accurately explains our data which are compatible with the shared epitope hypothesis and suggest a dosage effect among shared epitope positive HLA-DRB1 alleles, double dose genotypes carrying higher ORs than single dose genotypes.

Conclusion: HLA-DRB1 genotypic risk for developing ACPA positive RA is influenced by both HLA-DRB1 alleles in genotype. We provide an HLA-DRB1 genotypic risk table for ACPA positive RA.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exist.

Figures

Figure 1
Figure 1. ORs could be calculated for 102 out of 136 possible HLA-DR genotypes.
Here (for clarity) we only represent the ORs for the 91 most common (at least 10 patients plus controls). Genotypes highlighted in red have ORs significantly higher than 1, genotypes highlighted in green have ORs significantly lower than 1, genotypes non highlighted: OR not significantly different from 1.
Figure 2
Figure 2. HLA-DRB1 genotype risk for ACPA positive RA.
Red boxes: OR significantly higher than 1. Green boxes: OR significantly less than 1.
Figure 3
Figure 3. Influence of second allele on genotypic ORs in genotypes with HLA-DRB1*04SE, HLA-DRB1*04∶01, HLA-DRB1*01.
Genotypes with HLA-DRB1*04SE and HLA-DRB1*04∶01 keep high ORs despite modulation by second allele.
See this image and copyright information in PMC

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