AB0033 The identification of IL-17A+, IL-17RA+ and IL-17RC+ lymphoid and myeloid cells in blood of treatment naÏve early and in synovial fluid of established psoriatic arthritis patients

Abstract

BackgroundInterleukin (IL)-17A is a pro-inflammatory cytokine and is involved in the pathogenesis of psoriatic arthritis (PsA) (1,2). Various cells can produce IL-17A. However, it is not clear which cell types in PsA patients are responsible for the production of IL-17A. In addition, the expression of IL-17RA and IL-17RC on different cell types is not well defined.ObjectivesTo identify IL-17A, IL-17RA and IL-17RC positive cells in blood of first diagnosed PsA patients with arthritis and in synovial fluid of established PsA patients with active disease.MethodsFresh blood was taken from first diagnosed DMARD and steroid naïve PsA patients (n=10), having arthritis in 1 or more joints (PsA blood). The diagnosis was made by a rheumatologist according to the CASPAR-criteria. In addition, fresh synovial fluid was obtained from established PsA patients (PsA SF) with active disease (n=10) and treated with either methotrexate (n=3) or adalumimab (n=3) or NSAIDs (n=4). Multicolor flow cytometric analysis was performed on PsA blood and PsA SF. For the detection of IL-17A, IL-17RA or IL-17RC the following antibodies were used: IL-17A-PE (eBioscience), IL-17RA or isotype control IgG1k (both Biolegend), IL-17RC or isotype control IgG2b (both R&D systems). The following markers were used to discriminate between different cell populations: T cell subsets (CD3, CD4, CD8, CD45RO, CCR6, TCRγδ), B cells (CD19), NK cells (CD15-CD16+), neutrophils (CD15+CD16+), monocytes (CD33+CD14+CD16+/-), mast cells (CD117+FcER1a+) and eosinophils (CD15+FcER1a+).ResultsDifferent lymphoid and myeloid cell types were IL-17A positive in PsA blood of first diagnosed PsA patients such as CD3+, TCRγδ+, CD4+, CD8+ lymphoid cells, CD14+ monocytes and eosinophils. In PsA SF of established PsA patients TCRγδ+ T cells, neutrophils, NK cells and eosinophils were IL-17A positive.In both groups, no difference in expression of IL-17RA and IL-17RC was found on CD4+, CD8+, CD4+CD45RO+CCR6+/-, TCRγδ+ and CD19+ lymphoid cells compared to their isotype control. In contrast, the expression of IL-17RA and IL-17RC was increased compared to their isotype control on neutrophils and monocytes in PsA blood and on neutrophils, monocytes, mast cells and eosinophils in PsA SF.ConclusionsThese preliminary data show that not only lymphoid cells but also specific myeloid cell types may be sources of IL-17A in PsA. Furthermore, not lymphoid cells but IL-17RA/IL-17RC positive myeloid cells such as monocytes, neutrophils, mast cells and eosinophils may be potential target cells for IL-17A.Together, these data suggest a more broad, but specific IL-17A-IL-17RA/RC signaling network between different cell types important in the IL-17A-driven pathogenesis of PsA.References Lubberts E. Nat Rev Rheumatol 2015, 11: 415–29.McInnes IB, et al. Lancet 2015, 386: 1137–46. Disclosure of InterestNone declared