T cells, synoviocytes, and granzyme B+ cytotoxic cells associated with joint damage in recent onset RA

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Ann Rheum Dis. 2004 May;63(5):483-8.

T cells, fibroblast-like synoviocytes, and granzyme B+ cytotoxic cells

are associated with joint damage in patients with recent onset

rheumatoid arthritis.

Kraan MC, Haringman JJ, Weedon H, Barg EC, MD, Ahern MJ, Smeets

TJ, Breedveld FC, Tak PP.

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@...

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.

PMID: 15082476

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