HLA-DMA*0103 and HLA-DMB*0104 alleles as novel prognostic factors in rheumatoid arthritis.

OBJECTIVE

To evaluate HLA-DM alleles as markers for disease severity in rheumatoid arthritis (RA).

METHODS

Two distinct cohorts of patients with RA were oligotyped for HLA-DB1 and HLA-DM genes using PCR amplified genomic DNA with sequence specific oligonucleotide probes. Cohort 1 comprised 199 unselected patients with RA (mean (SD) age 45.5 (13.5) years; disease duration 11.9(8.8) years), whose disease severity was assessed using Larsen score on hand and foot radiographs. Cohort 2 comprised 95 patients with severe RA and 70 patients with benign RA according to the Larsen method.

RESULTS

In cohort 1, after stratification according to DRB1 genotypes, patients positive for HLA-DMA0103 and negative for HLA-DRB104 tended to have greater articular damage on hands and wrists (p = 0.07 by Mann-Whitney U test) and reached statistical significance for the Larsen score per year (p = 0.05). This association between HLA-DMA0103 and articular damage was especially observed in patients with HLA-DRB101. Similarly, HLA-DMB0104 positive patients had higher Larsen score on hands and wrists (p = 0.02). This association was even stronger in DRB104 positive patients (p = 0.005). In cohort 2, HLA-DMA0103 was associated with severe RA in patients negative for HLA-DRB104 (OD = 5.4; p = 0.014). HLA-DMB*0104 allele frequency tended to be higher in patients with severe RA but without reaching significance.

CONCLUSION

This is the first study evaluating the role of HLA-DM genes in the severity of RA. Our results suggest that HLA-DMA0103 and HLA-DMB0104 alleles may represent new genetic markers of RA severity. The HLA-DMA0103 allele tends to be associated with patients with RA negative for DRB104 and could predict a more severe form of disease especially in HLA-DRB101 positive patients. The HLA-DMB0104 allele could have an additive effect in HLA-DRB1*04 patients. Combined determination of HLA-DM and HLA-DRB1 alleles could facilitate identification of patients likely to have a poor disease course.