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

R Goldbach-Mansky¹, S Suson¹, R Wesley¹, C E Hack², H S El-Gabalawy³, P P Tak⁴

¹ Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
² Sanquin Research at the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, Netherlands
³ Division of Rheumatology, University of Manitoba, Winnipeg, Manitoba, Canada
⁴ Division of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Netherlands

Correspondence to:
Dr Paul P Tak
Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, F4-218, PO Box 22700, 1100 DE Amsterdam, Netherlands; p.p.tak{at}amc.uva.nl

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.

Abbreviations: ACR, American College of Rheumatology; CTL, cytotoxic T lymphocyte; DMARD, disease modifying antirheumatic drug; ESSG, European Spondylarthropathy Study Group; NIAMS, National Institute of Arthritis and Musculoskeletal and Skin Diseases; PCR-SSP, polymerase chain reaction–sequence specific primer; RF, rheumatoid factor; SpA, spondylarthropathy; UA, undifferentiated arthritis

Keywords: granzyme B; rheumatoid arthritis; rheumatoid factor

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