HLA-DRB1 genotypes and the risk of developing anti citrullinated protein antibody (ACPA) positive rheumatoid
Nathalie Balandraud1, Christophe Picard, Denis Reviron
1Rhumatologie, Hôpital Sainte Marguerite, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Insights
This study identifies specific HLA-DRB1 genotypes that increase the risk of developing anti-citrullinated protein antibody (ACPA) positive rheumatoid arthritis (RA). The findings provide a detailed risk table for ACPA-positive RA based on HLA-DRB1 genetic variations.
Area of Science:
- Immunogenetics
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is an autoimmune disease.
- Anti-citrullinated protein antibody (ACPA) positivity is a key marker for RA.
- HLA-DRB1 genotype is a known risk factor for RA.
Purpose of the Study:
- To establish a comprehensive table of rheumatoid arthritis (RA) risk based on human leukocyte antigen (HLA)-DRB1 genotypes.
- To quantify the association between specific HLA-DRB1 genotypes and the development of anti-citrullinated protein antibody (ACPA) positive RA.
Main Methods:
- Human leukocyte antigen (HLA)-DRB1 genotyping was performed on 857 patients with ACPA-positive rheumatoid arthritis (RA) and 2178 controls.
- Odds Ratios (OR) were calculated for 106 distinct HLA-DRB1 genotypes, representing 97% of the study population.
Main Results:
- HLA-DRB1 genotypic odds ratios for developing ACPA-positive RA varied significantly, ranging from 28 to 0.19.
- Specific genotypes, including HLA-DRB1*04SE, HLA-DRB1*04:01, and HLA-DRB1*01, were associated with a high risk of RA.
- A dosage effect was observed, with double-dose genotypes conferring higher odds ratios than single-dose genotypes, supporting the shared epitope hypothesis.
Conclusions:
- The risk of developing ACPA-positive RA is influenced by the combination of both HLA-DRB1 alleles within an individual's genotype.
- A detailed HLA-DRB1 genotypic risk table for ACPA-positive RA has been generated, aiding in risk assessment.
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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