Immunogenetic markers and seropositivity predict radiological progression in early rheumatoid arthritis independent of disease activity

• Published in: Journal of rheumatology 2001-04, Vol.28 (4), p.735-744
• Main Authors: KALTENHÄUSER, Sylke, WAGNER, Ulf, SCHUSTER, Ernst, WASSMUTH, Ralf, ARNOLD, Sybille, SEIDEL, Wolfram, TRÖLTZSCH, Michael, LOEFFLER, Markus, HÄNTZSCHEL, Holm
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Arthritis, Rheumatoid - diagnostic imaging; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - physiopathology; Arthrography; Biological and medical sciences; Biomarkers; Cohort Studies; Disease Progression; Diseases of the osteoarticular system; Epitopes; Female; Genetic Markers; HLA-DR4 Antigen - genetics; Humans; Inflammatory joint diseases; Male; Medical sciences; Middle Aged; Prognosis; Prospective Studies; Severity of Illness Index; Time Factors
• ISSN: 0315-162X; 1499-2752

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). CONCLUSION: 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.