Immunogenetic markers and seropositivity predict radiological progression in early rheumatoid arthritis independent of disease activity.
OBJECTIVE
A prospective clinical study of patients with recent onset rheumatoid arthritis (RA) to examine the relationship between inflammatory disease activity and joint destruction in a 4 year followup, and to evaluate prognostic markers for severe joint erosions early in the disease.


METHODS
Eighty-seven patients with RA according to the American College of Rheumatology criteria and a disease duration < 2 years were followed for an observation time of 2 to 4 years (mean 3.1 yrs). Variables of clinical and laboratory disease activity were monitored, and HLA-DRB1 alleles were determined. Hand and foot radiographs were taken every 6 months.


RESULTS
Multivariate analysis of independent contributions of covariates to progression of joint destruction resulted in a mixed effect regression model with significant influences for the presence of a shared epitope (SE) positive DR4 allele (SE+ DR4+; p = 0.007), rheumatoid factor (RF) IgA (p = 0.01), and sex (p = 0.059), but not for clinical variables or acute phase reactants. The odds ratio to reach a Larsen score above 32 during the observation period of 4 years was increased in patients positive for RF IgM (OR 2.7, p = 0.019), for the shared epitope on a DR4 allele (OR 8.6, p < 0.005), and in patients with erosions already at study entry (OR 11.9, p = 0.001). The highest sensitivity and specificity for the prediction of severe bone destruction (84% and 79%) were found when the presence of either a SE+ DR4 allele or of early erosions was used as a prognostic marker (OR 20.4, p < 0.0001).


CONCLUSIONS
Our results show the pace of joint destruction in RA to be influenced by the presence of SE+ DR4 alleles, RF production, and sex and by the presence of erosive disease at presentation. Those prognostic markers exert their influence independently from the inflammatory disease activity.
Kaltenhäuser
S
S
Department of Medicine IV, University of Leipzig, Germany.
Wagner
U
U
Schuster
E
E
Wassmuth
R
R
Arnold
S
S
Seidel
W
W
Tröltzsch
M
M
Loeffler
M
M
Häntzschel
H
H
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D001175:Arthrography; D015415:Biomarkers; D015331:Cohort Studies; D018450:Disease Progression; D000939:Epitopes; D005260:Female; D005819:Genetic Markers; D015804:HLA-DR4 Antigen / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors
D015415:Biomarkers; D000939:Epitopes; D005819:Genetic Markers; D015804:HLA-DR4 Antigen