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. 2004 Oct 7;64(5):715–721. doi: 10.1136/ard.2003.007039

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

R Goldbach-Mansky 1, S Suson 1, R Wesley 1, C Hack 1, H El-Gabalawy 1, P Tak 1
PMCID: PMC1755472  PMID: 15471892

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.

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Figure 1.

Figure 1

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 Box and whisker plots: boxes signify 25th and 75th centiles, whiskers 10th and 90th centiles, crosses are means, dots are outliers. Comparisons were made between disease groups. Means and medians are given, as well as p values for parametric (ANOVA) and non-parametric (Kruskal–Wallis) analyses. Granzyme B values (for patients with levels >10 pg/ml) are computed as log granzyme concentrations in pg/ml. RA, rheumatoid arthritis; SpA, spondylarthropathy; UA, undifferentiated arthritis.

Figure 2.

Figure 2

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 (A) Comparison of log granzyme B concentrations between RF+ and RF– cases (all arthropathies). (B) Comparison of log granzyme B concentrations between RF+ and RF– cases (rheumatoid arthritis cases only). Box and whisker plots: boxes signify 25th and 75th centiles, whiskers 10th and 90th centiles, crosses are means, dots are outliers. Comparisons were made between disease groups. Means and medians are given, as well as p values for parametric (ANOVA) and non-parametric (Kruskall–Wallis) analyses. Granzyme B values (for patients with levels >10) are computed as log granzyme concentrations in pg/ml. RA, rheumatoid arthritis; RF+, rheumatoid factor positive; RF–, rheumatoid factor negative.

Selected References

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