BackgroundJuvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Our group has recently demonstrated that extended oligoarticular and polyarticular JIA mostly evolve to a rheumatoid arthritis (RA)-like phenotype in adulthood. Disturbances in B cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cell immune responses are associated with RA pathogenesis, but their exact role in JIA development is poorly understood.ObjectivesThe main goal of this study was to characterize the frequency and phenotype of B, Tfh and Tfr cells in peripheral blood and the cytokine environment present in circulation in children with with extended oligoarticular JIA (eoJIA) and polyarticular JIA (pJIA) when compared to healthy controls, children with persistent oligoarticular JIA (poJIA) and adult JIA patients.MethodsBlood samples were collected from 105 JIA patients (children and adults) and 50 age- and gender-matched healthy individuals. Peripheral blood mononuclear cells were isolated and the frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry. Serum levels of APRIL, BAFF, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, IL-22, IFN-γ, PD-1, PD-L1, sCD40L, CXCL13 and TNF were measured by multiplex bead-based immunoassay and/ or ELISA in all groups included.ResultsThe frequency of B, Tfh and Tfr cells was similar between JIA patients and controls. Children with eoJIA and pJIA, but not poJIA, had significantly lower frequencies of plasmablasts, regulatory T cells and higher levels of Th17-like Tfh cells in circulation when compared to controls. Furthermore, APRIL, BAFF, IL-6 and IL-17A serum levels were significantly higher in pediatric eoJIA and pJIA patients when compared to controls. These immunological alterations were not found in adult JIA patients in comparison to controls.ConclusionChanges in B and Tfh cell subpopulations, but not in Tfr cells, were found in peripheral blood of children with eoJIA and pJIA when compared to controls. Our results suggest a potential role and/ or activation profile of B and Th17-like Tfh cells in the pathogenesis of eoJIA and pJIA, but not poJIA.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
BackgroundJuvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children1. Our group has recently demonstrated that extended oligoarticular (eoJIA) and polyarticular JIA (pJIA) mostly evolve to a rheumatoid arthritis (RA) like phenotype in adulthood2. Disturbances in B cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cell immune responses are associated with the pathogenesis of RA3,4, but their exact role in JIA development is not entirely known.ObjectivesThe main goal of this study was to characterize the frequency and phenotype of B, Tfh and Tfr cells in peripheral blood of children with eoJIA and pJIA when compared to healthy controls and children with persistent oligoarticular JIA (poJIA).MethodsBlood samples were collected from children with eoJIA (n=5), pJIA (n=11) and poJIA (n=19) treated with disease modifying anti-rheumatic drugs. A group of age-matched healthy individuals (n=8) was used as control. Peripheral blood mononuclear cells were isolated and the frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry.ResultsThe frequency of B, Tfh and Tfr cells was similar between JIA patients and controls. Children with eoJIA and pJIA, but not poJIA, had higher levels of naïve B cells and lower frequencies of post-switch memory B cells and plasmablasts when compared to controls. Th17-like Tfh cells were significantly increased in all JIA patients when compared to controls. B cell phenotype was similar between JIA patients and controls, but a reduced activated phenotype of Tfh cells was observed in JIA patients in comparison to controls.ConclusionChanges in B and Tfh cell subpopulations, but not in Tfr cells, were found in peripheral blood of children with JIA when compared to controls. The increased frequencies of Th17-like Tfh cells detected in JIA when compared to controls suggests a potential role of these cells in JIA pathogenesis. A treatment effect on the activation state of B, Tfh and Tfr cells cannot be excluded.References[1]Ravelli, A. & Martini, A. Juvenile Idiopathic Arthritis. Lancet 369, 767–778 (2007).[2]Oliveira-ramos, F. et al. Juvenile idiopathic arthritis in adulthood: fulfillment of classification criteria for adult rheumatic diseases, long-term outcomes and predictors of inactive disease, functional status and damage. 1–10 (2016)[3]Moura, R. A., Graca, L. & Fonseca, J. E. To B or not to B the conductor of rheumatoid arthritis orchestra. Clin. Rev. Allergy Immunol. 43, 281–291 (2012).[4]Deng, J., Wei, Y., Fonseca, V. R., Graca, L. & Yu, D. T follicular helper cells and T follicular regulatory cells in rheumatic diseases. Nat. Rev. Rheumatol. 15, 475–490 (2019).AcknowledgementsC. Tomé was supported by a fellowship from Fundação para a Ciência e a Tecnologia (FCT) (PD/BD/135520/2018), Portugal. This work was supported by a grant from Sociedade Portuguesa de Reumatologia.Disclosure of InterestsNone declared.
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