Patients chosen for treatment with cyclosporine because of severe rheumatoid arthritis are more likely to carry HLA-DRB1 shared epitope alleles, and have earlier disease onset.
OBJECTIVE
To determine whether patients with rheumatoid arthritis (RA) selected for treatment with cyclosporin A (CSA) because of severe disease are more likely to carry HLA-DRB1 alleles encoding the conserved "shared epitope" (SE) sequence.


METHODS
The majority of patients (n = 178) were currently being treated with methotrexate (MTX), either alone or in combination with chloroquine and/or CSA. In about 30% of patients, treatment with CSA had been initiated because of limited response to MTX or MTX and chloroquine. Patients were treated as clinically indicated without knowledge of their HLA-DRB1 status. HLA-DRB1 typing was by a reverse dot blot method.


RESULTS
Patients that had been treated with CSA were significantly more likely to carry an SE allele than patients not treated with CSA (81.5% vs 60.5%; OR 2.9, p = 0.006). Patients with 2 SE alleles were the most likely to have been treated with CSA. Results were still significant after correction for age, sex, and disease duration in a logistic regression model. There was no association between rheumatoid factor positivity and requirement for CSA therapy. Examination of individual SE alleles by multiple logistic regression analysis indicated that the strongest association was with presence of HLA-DRB1**0401 (p = 0.004). The DRB1*0401/*0404 genotype provided the greatest risk of requiring CSA treatment. Patients selected for CSA treatment had developed RA at a significantly earlier age than those not requiring CSA (44.4 vs 51.3 yrs; p = 0.004).


CONCLUSIONS
Patients requiring treatment with CSA because of severe RA were significantly more likely to carry an SE allele than patients not requiring such treatment. CSA treated patients were also more likely to have had earlier age of disease onset. These data provide further evidence that bearing the SE (particularly 2 alleles) is associated with development of severe RA.
González-Gay
Miguel A
MA
Staffordshire Rheumatology Centre, Stoke-on-Trent, Staffordshire, UK.
Hajeer
Ali H
AH
García-Porrúa
Carlos
C
Dababneh
Adele
A
Thomson
Wendy
W
Ollier
William E R
WE
Mattey
Derek L
DL
D000328:Adult; D017668:Age of Onset; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D001175:Arthrography; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use*; D004247:DNA / Q000032:analysis; D004359:Drug Therapy, Combination; D000939:Epitopes; D005260:Female; D005787:Gene Frequency; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007596:Joints / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000032:analysis; D012720:Severity of Illness Index
D018501:Antirheumatic Agents; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D004247:DNA; D012217:Rheumatoid Factor