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

Ann Rheum Dis. 2005 May;64(5):715-21. doi: 10.1136/ard.2003.007039. Epub 2004 Oct 7.

Abstract

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Arthritis / diagnostic imaging
  • Arthritis / enzymology
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / enzymology*
  • Arthritis, Rheumatoid / pathology
  • Biomarkers / blood
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granzymes
  • HLA-DR Antigens / blood
  • Histocompatibility Testing
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Radiography
  • Rheumatoid Factor / blood*
  • Serine Endopeptidases / blood*
  • Severity of Illness Index
  • Spondylarthropathies / diagnostic imaging
  • Spondylarthropathies / enzymology

Substances

  • Biomarkers
  • HLA-DR Antigens
  • Rheumatoid Factor
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases