engleski

Regulatory T cells in juvenile idiopathic arthritis

Introduction: Regulatory T (TR) cells play a mayor role in the homeostasis of the immune system. Different populations of TR cells have been described, including so-called “ naturally occurring” CD4+CD25+ T cells and IL-10-producing TR1 cells. Animal studies have shown that removal or inactivation of CD4+CD25+ T cells can break natural self-tolerance ; leading to development of autoimmune diseases, while reintroduction of this subset of T cells prevented diseases. Although the recent reports confirmed the role of TR cells in various human pathological conditions but surprisingly little is know about the TR cells in juvenile idiopathic arthritis (JIA). Aim: To explore the level of TR cells in peripheral blood of patients with JIA in relation to disease severity. Patients and Methods: Thirty-four JIA patients (20 with oligoarticular, 9 with polyarticular, and 5 with systemic JIA) and 23 healthy children were enrolled. The diagnosis was established according to the ILAR criteria. Peripheral blood samples were obtained in active and inactive phase of the disease and analysed by means of flow cytometry. The relative and absolute numbers of CD4+CD25+ cells, as well the cells with presumed TR phenotype (CD4+CD25++ and CD4+CD25++CCR4+) were measured. The groups were compared using ANOVA, followed by Student-Newman- Keuls post hoc test. The α -level was set at 0.05. The study was approved by the Ethics Committee of the Zagreb University School of Medicine. Results: Children with the systemic type of JIA had significantly higher levels of CD4+CD25+ lymphocytes than children with other types of JIA or the healthy controls (P<0.05 ; ANOVA) (Table 1). In addition, the level of CD4+CD25+ lymphocytes during remission was higher in patients with polyarticular JIA than in children with oligoarticular JIA or in healthy children (P<0.05 ; ANOVA). The proportions of CD4+CD25++ and CD4+CD25++CCR4+ lymphocytes in the inactive phase of oligoarticular and polyarticular JIA were decreased in comparison to the healthy controls (P<0.05 ; ANOVA), whereas the differences during the active phase were not significant. Conclusion: We found no differences between the JIA patients and healthy children with respect to the regulatory T cell populations (defined both as CD4+CD25++ or CD4+CD25++CCR4+) during the active phase of disease. On the other hand, healthy children had more regulatory T cells compared to patients with JIA in remission. Although the difference between the control group and children with systemic JIA was not significant, the lack of statistical difference was probably due to the relatively small sample size. The increased proportions of CD4+CD25+ lymphocytes in the systemic and polyarticular forms of JIA indicate the inflammatory activity of the immune system during the clinically “ silent” phase of disease. Taken together, our data suggest that the reduction of TR cell population during the remission of JIA might make the patients prone to the break of immune tolerance and activation of the disease. Once the autoimmune process is activated the TR cells might not be able to control it, in spite of increase of their proportion. The enrolment of further patients should help to clarify this issue.

regullatory T cells ; juvenile idiopathic arthritis

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