RHEUMATOLOGY, 2024 (SCI-Expanded)
Objectives: JIA is the most common rheumatic disease of childhood; the pathogenesis is associated with T-cell activation. T-cell activation can be counterbalanced by signals generated by inhibitory receptors (IRs) such as CTLA-4, PD-1, LAG-3 and TIM-3. Here, we identify the role of IRs in the pathogenesis of different JIA subtypes. Methods: In total, we included 67 oligoarticular JIA, 12 IgM-RF negative polyarticular JIA, 17 enthesitis-related arthritis, 11 systemic JIA patients and 10 healthy controls. We collected plasma (and SF) samples from the patients either at the onset or during a flare of their disease. We measured the soluble levels of co-IRs (IL-2R alpha, 4-1BB, CD86, TGF-beta 1, CTLA-4, PD-L1, PD-1, TIM-3, LAG- 3, Galectin-9) by cytometric bead array kits and their cellular expression (PD-1, CTLA-4, TIM-3, LAG-3) by flow cytometry. We compared the plasma levels and cellular expressions of different co-IRs within different JIA subgroups. Results: The polyarticular JIA group was different from the three other examined JIA subgroups, having higher levels of plasma sCTLA-4 (P < 0.001), sPD-1 (P < 0.05) and s4-1BB (P < 0.05) when compared with the other JIA subgroups and healthy controls. We analysed the cellular surface expression of different co-IRs on the peripheral blood mononuclear cells of different JIA subtypes. Similar to plasma levels, both the percentage (P < 0.05) and the mean fluorescence intensity (P < 0.01) of CTLA4 expression were higher in the polyarticular JIA subgroup. Conclusion: This is the first report studying the expression profile of different co-IRs in different subtypes of JIA. Polyarticular JIA patients had a different co-IR profile, having more CTLA-4, PD-1 and 4-1BB in their plasma than the other subtypes of JIA.