title: Genetic typing of patients with inflammatory arthritis at presentation can be used to predict outcome.
abstract: OBJECTIVE
  To test the hypothesis that genetic characterization of patients at the time they present with inflammatory arthritis can predict subsequent destructive disease.
  
  
  METHODS
  We evaluated 177 patients with early arthritis. Patients were serologically tested for rheumatoid factor (RF) and were DNA oligotyped for the presence of conserved base sequences in the third hypervariable region (HVR3) of the DRB1 gene, previously shown to be associated with severe rheumatoid arthritis (RA). Homozygosity in the patient's genotype was confirmed using restriction fragment length polymorphism analysis. The main outcome measure was radiologic erosions at 1 year.
  
  
  RESULTS
  At presentation, 120 patients fulfilled the American College of Rheumatology 1987 criteria for RA, 64% of whom possessed the conserved base sequences, compared with 45% of 347 healthy controls (P < 0.001) and with 56% of 57 patients with other inflammatory arthritis (P not significant). Within the RA population, the frequency of Dw4/Dw14 compound heterozygotes was disproportionately increased. The presence of either HVR3 or RF had a relative risk of 13.49 for erosions, with a sensitivity of 95% (specificity 39%); the presence of both HVR3 and RF had a relative risk of 8.13, with a specificity of 88% (sensitivity 53%). All but 1 patient with the Dw4/Dw14 genotype developed erosions within 1 year.
  
  
  CONCLUSIONS
  Knowledge of a patient's HLA-DR type and RF status allows clinically useful prediction of erosive disease; patients possessing Dw4/Dw14 represent a particularly high-risk subgroup.
authors.affiliation: University of Birmingham, UK.
authors.forename: A
authors.initials: A
authors.lastname: Gough
authors.forename: J
authors.initials: J
authors.lastname: Faint
authors.forename: M
authors.initials: M
authors.lastname: Salmon
authors.forename: A
authors.initials: A
authors.lastname: Hassell
authors.forename: P
authors.initials: P
authors.lastname: Wordsworth
authors.forename: D
authors.initials: D
authors.lastname: Pilling
authors.forename: A
authors.initials: A
authors.lastname: Birley
authors.forename: P
authors.initials: P
authors.lastname: Emery
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005500:Follow-Up Studies; D005787:Gene Frequency; D005802:Genes, MHC Class II; D005838:Genotype; D006681:HLA-D Antigens / Q000097:blood; D006684:HLA-DR Antigens / Q000235:genetics*; D006579:Heterozygote; D006650:Histocompatibility Testing; D006720:Homozygote; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D012217:Rheumatoid Factor / Q000097:blood
chemical_list: D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D007135:Immunoglobulin Variable Region; D012217:Rheumatoid Factor