ISR Autumn Meeting 2019
1st Place Scientific Oral Presentation
Increased T Cell Plasticity with Dysregulation of Tfh, Tph and Treg Cell Responses in Children with JIA and Down Syndrome-associated Arthritis.
Foley C*1, 2, Floudas A*2, Canavan M2, Monika Biniecka4, MacDermott EJ1, Veale DJ4, Mullan RH3, Killeen OG1, Fearon U2.
1National Centre for Paediatric Rheumatology (NCPR), Our Lady’s Children’s Hospital Crumlin (OLCHC) 2 Molecular Rheumatology, Trinity Biomedical Sciences Institute, TCD 3Dept of Rheumatology, Tallaght University Hospital, TCD 4EULAR Centre of excellence, Centre for Arthritis and Rheumatic Diseases, St Vincent’s University Hospital, UCD.
Juvenile idiopathic arthritis (JIA) is the most common inflammatory arthritis in children, however an aggressive, erosive and previously underdiagnosed arthritis of little known immunological mechanism, occurs 20-times more frequently in children with Down syndrome (Trisomy 21-T21). We have recently described for the first time the clinical features of DA, this study characterises T-and B-cell polyreactivity, T follicular helper (Tfh), pathologically expanded T helper (Tph) and regulatory (Treg) T cell responses and synovial inflammation in Down syndrome-associated Arthritis (DA).
Characterization of B cell subpopulation distribution in children with DA, JIA, T21 and healthy controls.
Identification and enumeration of plastic and poyreactive Tfh, Tph and Th cell responses in children with DA.
Evaluation of potential Tregulatory cell deficit and synovial inflammation in children with DA.
Multiparametric flow-cytometric analysis, SPICE algorithm and tsNE were utilised to examine peripheral blood B-cell populations and T-cell cytokine responses following in vitro stimulation in children with DA, JIA, T21 and healthy controls (HC). Tfh and Tph cell frequency and origin, in addition to Treg cell frequency were also evaluated. Synovial inflammation was assessed by immunohistology.
Expansion of IgM-only memory B-cells was demonstrated in DA compared to JIA, paralleled by decreased frequency of transitional B-cells. T-cell responses in DA were characterised by marked functional plasticity, evident by the increased frequency of polyfunctional CD8+ and CD161+ Th cells, positive for TNF-α, IFN-γ, IL-17A, or GM-CSF compared to all other groups. Significant expansion of CXCR3+CCR6+ (Th1/Th17) Tfh cells and CXCR3+CCR6+ Tph cells, paralleled by decreased CXCR3-CCR6- (Th2) Tfh was observed in children with DA compared to HC and T21. Naïve and memory Treg cells were significantly reduced in DA compared to T21, with a significant reduction in the naïve/memory Treg cell ratio. Marked synovial-tissue inflammation with increased T-and B-cell infiltration were demonstrated in children with DA compared to JIA.
DA is more common and more aggressive than JIA. It is characterised by increased T cell plasticity and polyfunctional Th, Tfh and Tph-cell responses, reduced Treg cell frequency and increased synovial-inflammation, which are distinct from JIA and T21.