RESUMO
BACKGROUND: Juvenile idiopathic arthritis pathogenesis involves a large number of different immune system cells, which are both sources and targets of chemokines, that affect not only their migration but also survival, proliferation, differentiation, production of all cytokine types, degranulation, and also directly stimulating or suppressing angiogenesis. Studyingthe contribution of chemokines to this disease pathogenesis will make it possible to identify new sensitive and specific markers for its diagnosis and subsequent dynamic monitoring of treatment effectiveness. The study aimed to identify a list of the most informative diagnostic markers from a wide range of juvenile idiopathic arthritis patients' blood plasma chemokines. METHODS: The case-control study included 40 diagnosed pathology patients and 20 healthy agematched children. The content of MCP-1/CCL2, MCP-3/CCL7, MIG/CXCL9, MIP-1α/CCL3, MIP-1ß/CCL4, RANTES/CCL5, IFN-γ, IP-10/CXCL10, and MDC/CCL22 were measured by enzyme- linked immunosorbent assay in blood plasma of each person. RESULTS: The following chemokines were included in the list of the most promising diagnostic markers: MCP-1, MIP-1α, MIG, RANTES, and IFN-γ. Their blood plasma content in patients with a diagnosed pathology was from 3 to 60 times (MIG) higher than in the conditionally healthy group. Their sensitivity and specificity exceeded 90%. CONCLUSION: An increase in their content leads to active monocytes/macrophages migration to the site of inflammation, where they suppress effector T-cell activity by binding suppressor exosomes and activate B-cells by autoantigens presentation received due to joint tissue destruction. This allows us to speak about the predominance of the Th1-mediated immune response during the development of studied disease chronic inflammation.
RESUMO
Juvenile idiopathic arthritis (JIA) is a systemic autoimmune disease that affects the joints, leading to disability. Cytokines and signaling molecules expressed by the immune system cells play a key role in JIA pathogenesis. Understanding how their content changes during pathology development can open up new opportunities for its diagnosis and treatment. The blood plasma of 30 patients with JIA (14 males and 16 females with a mean age of 12.2 ± 4.1) and 20 relatively healthy individuals (10 males and 10 females with a mean age of 10.20 ± 5.85) was analyzed to determine the levels of cytokines using the MILLIPLEX® kit. An increase in interleukins (IL)-1α, 1ß, 2, 4, 5, 6, 7, 8, 9, 10, 13, 15, 17F, 22, and 27 and a decrease in IL-3 levels have been shown in patients with JIA. Levels of cytokines, which are important for B-cell activation and proliferation, are increased, while levels of T-cell activating factors remained similar to the control group. Based on our results, it can be assumed that the use of combination therapy aimed at inhibiting both nonspecific interleukins and cytokines that activate B-cells will be more effective for the treatment of JIA.