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T cells, fibroblast-like synoviocytes, and granzyme B+ cytotoxic cells are associated with joint damage in patients with recent onset rheumatoid arthritis

M C Kraan¹, J J Haringman¹, H Weedon², E C Barg¹, M D Smith², M J Ahern², T J M Smeets¹, F C Breedveld³, P P Tak¹

¹ Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands
² Department of Rheumatology, Repatriation General Hospital, Adelaide, South Australia
³ Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands

Correspondence to:
Correspondence to:
Dr P P Tak
Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, University of Amsterdam/Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; p.p.tak{at}amc.uva.nl

Objective: To determine immunohistological markers in synovial tissue of patients with early rheumatoid arthritis (RA) which are associated with unfavourable disease outcome.

Methods: Synovial tissue was obtained from 36 patients with RA within 1 year after the initial symptoms and before starting disease modifying antirheumatic drug treatment. Clinical, laboratory, and radiological assessments (Larsen score) were performed at the time of the biopsy and at the end of follow up (mean 58 months, range 38–72). 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 mild progression (n = 20; Larsen <2 points/year); group II with more severe progression (n = 16; Larsen 2 points/year). Regression analysis with a univariate model showed that the numbers of granzyme B+ cytotoxic cells (relative risk (RR) = 12, p = 0.003), T cells (RR = 11, p = 0.013), and FLS (RR = 10, p = 0.020) discriminated between groups I and II. A multivariate model demonstrated that the 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 patients with RA are related to the severity of joint damage. The data suggest a pathogenetic role for these cells in the process of joint damage.

Keywords: fibroblast-like synoviocytes; granzyme B; joint damage; rheumatoid arthritis; T cells

Abbreviations: CRP, C reactive protein; DAS, disease activity score; DMARDs, disease modifying antirheumatic drugs; ESR, erythrocyte sedimentation rate; FLS, fibroblast-like synoviocytes; HAQ, Health Assessment Questionnaire; HPF, high powered field; OPG, osteoprotegerin; RA, rheumatoid arthritis; RANKL, receptor activator NF-B ligand; RF, rheumatoid factor; RR, relative risk

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