Ann Rheum Dis 64:715-721 doi:10.1136/ard.2003.007039
  • Extended report

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

  1. R Goldbach-Mansky1,
  2. S Suson1,
  3. R Wesley1,
  4. C E Hack2,
  5. H S El-Gabalawy3,
  6. P P Tak4
  1. 1Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
  2. 2Sanquin Research at the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, Netherlands
  3. 3Division of Rheumatology, University of Manitoba, Winnipeg, Manitoba, Canada
  4. 4Division of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Netherlands
  1. 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;
  • Accepted 18 September 2004
  • Published Online First 7 October 2004


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.