W136 - Proinflammatory Memory CD4+ T Cell Markers Are Elevated in the Circulation of Patients with Juvenile Idiopathic Arthritis

Abstract Text: Juvenile idiopathic arthritis (JIA) is an autoimmune disease in children characterized by chronic inflammation of the joints. In patients with JIA, pro-inflammatory CD4+ helper T cells have been suggested to play an important role in driving synovial inflammation. However, only limited data on peripheral blood immune cell changes exist in JIA patients. We studied circulating immune cells, in particular the memory CD4+ T-cell compartment, using multiparameter flow cytometry to compare patients with JIA (n=77) to healthy age- and sex-matched controls (n=53). Interestingly, we detected an elevated frequency of circulating CD4+CXCR5-PD-1hi T peripheral (Tph) cells (p < 0.0001), a T-cell subset suggested to provide help to B cells in inflamed tissues in patients with JIA compared to controls. Moreover, increased frequencies of tumor necrosis factor-alpha (TNF-α) (p < 0.0001), interleukin (IL)-2 (p=0.0003), and interferon-gamma (IFN-γ) (p=0.0155) producing CD4+ memory T cells were detected in JIA patients compared to controls, when PBMCs were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin. In summary, the memory CD4+ T cell compartment in patients with JIA shows alterations, characterized by T-cell signatures linked to proinflammatory functions and enhanced T-cell-B-cell interactions. These signatures could potentially be utilized in the development of T-cell based biomarkers to monitor JIA disease activity.