Raised granzyme B levels are associated with erosions in patients with early rheumatoid factor positive rheumatoid arthritis

Background: Raised granzyme B in serum and synovium of patients with rheumatoid arthritis suggests a role for cytotoxic T cells and natural killer cells in the pathogenesis of this disease. Objective: To evaluate serum granzyme B in patients with early arthritis and correlate it with specific diagnosis and clinical indices of disease severity. Methods: 257 patients with inflammatory arthritis for less than one year (46% rheumatoid arthritis, 17% spondyloarthropathy, 37% undifferentiated arthritis) had a prospective clinical, serological, and radiographic evaluation. Granzyme B was measured in initial sera by ELISA. Patients were HLA typed for DR alleles using sequence specific primers. A logistic regression model was used to evaluate the potential prognostic value of serum granzyme B in predicting radiographic erosions after one year of follow up. Results: Granzyme B values were similar in rheumatoid arthritis, spondyloarthropathy, and undifferentiated arthritis. Concentrations were higher in rheumatoid factor (RF) positive patients than in RF negative patients ( mean (SD): 3.15 (0.92) v 2.89 (0.71) pg/ml; p< 0.05). After one year, erosions were present in 30% of patients in the overall cohort, and in 44% of patients with rheumatoid arthritis. In the entire cohort, serum granzyme B did not predict erosions independently. However, high granzyme B was an independent predictor of early erosions in patients with RF positive rheumatoid arthritis ( odds ratio = 4.83 (95% confidence interval, 1.13 to 20.59)) (p< 0.05). Conclusions: Granzyme B may be a useful prognostic marker in early rheumatoid arthritis and may provide important clues to the pathogenesis of this disease.