title: Association of HLA-DR with susceptibility to and clinical expression of rheumatoid arthritis: re-evaluation by means of genomic tissue typing.
abstract: The clinical expression of rheumatoid arthritis (RA) varies considerably among individual patients. Genetic variations in human leucocyte antigen (HLA) may influence clinical expression. We re-examined the association of HLA-DR with susceptibility to and clinical expression of RA using genomic tissue typing, since most studies were based on (less reliable) serological techniques. Seventy-eight patients with recent-onset RA, all participating in a clinical trial on therapeutic strategies, were HLA-DR typed by means of low-resolution genomic typing. Cumulative disease activity within the first 3 yr of disease was measured. Of the RA patients, 54% expressed DR4 (DR4+) vs 26% of healthy controls. Rheumatoid factor (RF)-positive patients had a higher cumulative disease activity than RF-negative patients. Patients who were either DR1+ or DR4+ had a higher cumulative disease activity than those who expressed neither DR1 nor DR4. This association was less obvious after correction for RF status. The association of DR52+ (DR3, 5, 6) and a lower cumulative disease activity could also not be demonstrated after correction for RF status. Among RF-negative patients, DR51+ (or DR2+) was associated with a higher cumulative disease activity. Other HLA-DR types (including DR1 and DR4 separately) were not associated with the severity of RA. DR4 was associated with susceptibility to RA in our patients; HLA-DR low-resolution genomic tissue typing did not yield additional information to RF status for the clinical identification of individual patients with a poor prognosis.
authors.affiliation: Rheumatic Research Foundation Utrecht, Department of Rheumatology and Clinical Immunology, University Hospital Utrecht, The Netherlands.
authors.forename: C H
authors.initials: CH
authors.lastname: Van Jaarsveld
authors.forename: H G
authors.initials: HG
authors.lastname: Otten
authors.forename: J W
authors.initials: JW
authors.lastname: Jacobs
authors.forename: A A
authors.initials: AA
authors.lastname: Kruize
authors.forename: H L
authors.initials: HL
authors.lastname: Brus
authors.forename: J W
authors.initials: JW
authors.lastname: Bijlsma
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005260:Female; D015894:Genome, Human; D006684:HLA-DR Antigens / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012217:Rheumatoid Factor / Q000097:blood
chemical_list: D006684:HLA-DR Antigens; D012217:Rheumatoid Factor