Background We have recently described that IL-15 induces higher CD69 expression on lymphocytes compared to several cytokines described in rheumatoid synovium. A growing body of evidence supports that these two molecules can play an important role in the perpetuation of synovitis in RA.
Objectives To determine IL-15 serum levels and the expression of CD69 on PBL from RA patients and to assess their possible correlation with several clinical and biological parameters.
Methods IL-15 and TNF-a serum levels were measured by ELISA (R&D Systems) and CD69 expression on PBL was assessed by flow cytometry, both in RA patients (n = 25) and healthy donors (n = 15). Each RA patient was evaluated at the time of sample collection for the following variables: morning stiffness (MS), pain visual analogic scale (0–100 mm), number of tender (TJC) and swollen (SJC) joints (Fuchs 28 joints count), patient and physician global disease activity assessment (GDA) in a Likert scale (0–4), ESR and CRP. Those patients that fulfilled 5 or more of the next criteria were considered to have an active disease: pain score > 25 mm; TJC > 5; SJC > 3; patient GDA > 1; physician GDA > 1; ESR > 25 mm and RCP > 0.8 mg/dl. DAS28 score was also calculated. Student t test and Pearson correlation test were applied for statistical analysis.
Results IL-15 and TNF-a serum levels from RA patients were significantly higher than that from healthy donors (314.6 ± 72.3 vs. 12.9 ± 3.1 pg/ml, p = 0.0001; and 233.1 ± 97.9 vs 74.2 ± 30 pg/ml, p = 0.06, respectively). The percentage of CD69 positive PBL in RA patients was also higher that in controls (12.6 ± 1.2 vs. 9.7 ± 0.8; p = 0.03). The percentage of CD69+ PBL correlated with DAS score (r = 0.382; p < 0.05). In addition, MS and TNF-a levels also correlated (r = 0.49; p = 0.015). Mean serum concentrations of IL15 and TNF-a in patients with active disease were higher than these cytokine levels in patients considered inactive (274 vs. 112.4 pg/ml and 337.6 vs. 211 pg/ml, respectively), although this difference did not reached statistical significance likely due to the low number of patients with inactive disease (n = 6).
Conclusion Our data showed a correlation between CD69 expression on PBL and clinical parameters, suggesting a pathogenic role for this molecule in RA. Further studies are needed to evaluate the clinical significance of elevated levels of IL15 in RA patients.
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