A2.15 Relative Overexpression of Transmembrane Versus Soluble TNF in Human and Experimental Spondyloarthritis

Abstract

Background Macrophages and their pro-inflammatory cytokines, including TNF, are pivotal mediators of chronic synovitis in rheumatoid arthritis (RA) as well as spondyloarthritis (SpA). Despite similar levels of synovial macrophage infiltration and similar clinical responses to TNF blockade in both diseases, SpA is characterised by a more pronounced infiltration with alternatively activated CD163+ macrophages and ongoing osteoproliferation. This study aimed to investigate whether these differences were related to a differential expression and/or function of TNF between both diseases. Methods Expression of transmembrane TNF (tmTNF) and soluble TNF (sTNF) was measured in IFN-γ, IL-4 or IL-10 polarised macrophages obtained from healthy donors. Expression of TNF and its receptors was measured in synovial fluid (SF) and synovial tissue biopsies (ST) of actively inflamed knee joints of SpA and RA patients. Mice transgenically overexpressing tmTNF (TgA86) were evaluated for spondylitis and arthritis. Results In vitro polarisation with IL-10 specifically induced the expression of CD163 on macrophages, mimicking the phenotype in SpA synovitis. IL-10 and IL-4 polarised macrophages secreted less TNF than classically, IFN-γ-polarised macrophages (p Conclusions tmTNF is relatively overexpressed by CD163+ alternatively polarised macrophages in SpA synovitis and leads to an axial and peripheral SpA phenotype in transgenic mice.