Synovial Tissue Response to Treatment with TNF Blockers in Peripheral Spondyloarthritis

Abstract

This review describes the synovial response to treatment in peripheral spondyloarthritis (SpA). A series of recent studies demonstrates that the synovial histopathology is largely homogenous between different SpA subtypes and can be strongly modulated by effective treatment such as tumor necrosis factor (TNF) blockade. This includes a dramatic reduction of the infiltration with inflammatory cells (with the intriguing exception of B lymphocytes and plasma cells), a modulation of structural features such as vascularity, intimal lining layer hyperplasia, and ectopic lymphoid neogenesis, and a down-regulation of a variety of mediators involved in tissue damage. The analysis of tissue response to targeted therapies appears to be a novel and elegant approach to study the immunopathology of human peripheral SpA in vivo. Moreover, detailed cellular and molecular analysis of synovial features allows to identify synovial biomarkers of clinical response to therapeutic interventions which can be used in future early phase clinical trials in SpA.

Keywords: Spondyloarthritis; Synovial biomarkers.; Synovial tissue; TNF blockade.

Fig. (1)

Distinct features of SpA synovitis. In comparison with RA, SpA synovitis displays less synovial lining layer hyperplasia (A), the abcens of intracellular citrullinated proteins (B), and the absence of HLA-DR4/HC gp-39 peptide complexes (C). Vascularity (D) as well as infiltration with polymorphonuclear cells (E) and CD163+ macrophages (F) is clearly increased in SpA. Depositions of uridic acid crystals (G), homogentisic acid (H), and hemosiderin (I) are typical for gout, ochronosis, and pigmented villonodular synovitis, respectively, and are not found in SpA synovitis.