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.
Goldbach-Mansky
R
R
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeltal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Suson
S
S
Wesley
R
R
Hack
C E
CE
El-Gabalawy
H S
HS
Tak
P P
PP
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