HLA-DMA0103 and HLA-DMB0104 alleles as novel prognostic factors in rheumatoid arthritis

• Published in: Annals of the rheumatic diseases Vol. 63; no. 12; pp. 1581 - 1586
• Main Authors: Morel, J, Roch-Bras, F, Molinari, N, Sany, J, Eliaou, J F, Combe, B
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.12.2004; BMJ; BMJ Publishing Group LTD
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid - diagnostic imaging; Arthritis, Rheumatoid - genetics; Biological and medical sciences; Child; Child, Preschool; disease modifying antirheumatic drug; Disease Progression; Diseases of the osteoarticular system; DMARD; Extended Report; Female; Foot - diagnostic imaging; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Hand - diagnostic imaging; Hands; HLA-D Antigens - genetics; HLA-DM; Humans; Inflammatory joint diseases; Lymphocyte receptors; major histocompatibility complex; Male; Medical prognosis; Medical sciences; MHC; Middle Aged; Patients; Phenotype; Prognosis; prognosis markers; Radiography; Retrospective Studies; rhematoid factor; Rheumatoid arthritis; Severity of Illness Index; Statistics, Nonparametric; T lymphocyte receptor; TCR; Rheumatoid factor; HLA-System; Allele; Chronic; Prognosis; Rheumatoid arthritis; Diseases of the osteoarticular system; Autoimmune disease; Inflammatory joint disease
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2003.012294

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-DMA*0103 and negative for HLA-DRB1*04 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-DMA*0103 and articular damage was especially observed in patients with HLA-DRB1*01. Similarly, HLA-DMB*0104 positive patients had higher Larsen score on hands and wrists (p = 0.02). This association was even stronger in DRB1*04 positive patients (p = 0.005). In cohort 2, HLA-DMA*0103 was associated with severe RA in patients negative for HLA-DRB1*04 (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-DMA*0103 and HLA-DMB*0104 alleles may represent new genetic markers of RA severity. The HLA-DMA*0103 allele tends to be associated with patients with RA negative for DRB1*04 and could predict a more severe form of disease especially in HLA-DRB1*01 positive patients. The HLA-DMB*0104 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.