Raised granzyme B levels are associated with erosions in patients with early rheumatoid factor positive rheumatoid arthritis.
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.
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeltal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
R
R
Goldbach-Mansky
S
S
Suson
R
R
Wesley
C E
CE
Hack
H S
HS
El-Gabalawy
P P
PP
Tak
D000328:Adult; D001168:Arthritis / Q000000981:diagnostic imaging / Q000201:enzymology; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D053804:Granzymes; D006684:HLA-DR Antigens / Q000097:blood; D006650:Histocompatibility Testing; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011859:Radiography; D012217:Rheumatoid Factor / Q000097:blood*; D012697:Serine Endopeptidases / Q000097:blood*; D012720:Severity of Illness Index; D025242:Spondylarthropathies / Q000000981:diagnostic imaging / Q000201:enzymology
D015415:Biomarkers; D006684:HLA-DR Antigens; D012217:Rheumatoid Factor; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases