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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

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


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.


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.


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.

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  • Rheumatoid Arthritis
  • Rheumatoid Arthritis Patient
  • Female Gender
  • Synovial Tissue
  • Disease Outcome