Predictive markers of disease outcome in synovial tissue: T cells, synovial fibroblasts, and granzyme B cytotoxic cells predict unfavorable outcome in patients with recent-onset rheumatoid arthritis

Objective

To determine immunohistological markers in synovial tissue of early rheumatoid arthritis (RA) patients, which could be used as predictors for disease outcome.

Methods

Synovial tissue was obtained from 36 RA patients within 1 year after the initial symptoms and before the initiation of treatment with any disease-modifying antirheumatic drug. Clinical, laboratory, and radiological assessment (Larsen score) was performed at the time of the biopsy and at the end of follow-up (mean 58 months, range 38–72 months). Immunohistological analysis was performed to detect T cells, B cells, plasma cells, fibroblast-like synoviocytes (FLS), macrophages, and granzyme B⁺ cytotoxic cells. The sections were evaluated by digital image analysis.

Results

Patients were divided into two groups based upon the radiological progression per year of follow-up: group I with moderate progression (n = 20) (by <2 points/year, Larsen score) and group II with pronounced progression (n = 16) (by ≥ 2 points/year, Larsen score). Regression analysis with a univariate model revealed that female gender (RR = 10.7, P = 0.015) and numbers of granzyme B⁺ cytotoxic cells (RR = 12, P = 0.003), T cells (RR = 10.1, P = 0.013), and FLS (RR = 10, P = 0.020) discriminated between groups I and II. A multivariate model demonstrated that female gender (RR = 78.42, P = 0.017) and numbers of T cells (RR = 1.2, P = 0.015) and FLS (RR = 1.4, P = 0.013) were independent discriminators between groups I and II.

Conclusion

The numbers of granzyme B⁺ cytotoxic cells, T cells, and FLS in synovial tissue of RA patients are related to the severity of joint damage and therefore may be useful prognostic markers of disease outcome in patients with recent-onset RA. In addition, the observations suggest a pathogenic role of these cells in the process of joint damage.