Identification of synovial biomarkers of response to experimental treatment in early‐phase clinical trials in spondylarthritis

Abstract

Conclusion. Changes in synovial macrophage subsets, PMN levels, and MMP-3 expression reflect response to treatment in SpA. The ability of these parameters to correctly identify effective therapy makes them interesting biomarkers for use in early-phase clinical trials in SpA.

Absence of a classically activated macrophage cytokine signature in peripheral spondylarthritis, including psoriatic arthritis

“…Paraffin-embedded tissue sections were stained with hematoxylin and eosin. Global cellular infiltration, vascularity, and synovial lining hyperplasia were assessed by semiquantitative scoring (scale of 0-3 for each feature) by 2 independent observers (BV and DB) who were blinded to the diagnosis and clinical data, as extensively described and validated previously (6)(7)(8)(9)(10)(11). The scores assigned by the 2 observers never differed by Ͼ1 point.…”

“…Of interest, the total number of macrophages is similar in RA and SpA synovitis, but the subset expressing the M2 surface marker, CD163 (4,5), is clearly increased in the latter (6)(7)(8). Moreover, this specific macrophage subset, but not the total number of macrophages, is correlated with disease activity and reflects response to treatment in SpA (9)(10)(11).…”

Juvenile Spondyloarthritis

“…The partial overlap with other JIA subtypes, with the exception of slightly lower vascularity in juvenile polyarthritis and higher inflammatory cell infiltration in juvenile oligoarthritis, emphasizes the need for further biologic characterization of JIA in order to define pathophysiologic, rather than phenotypic, subgroups (Kruithof, Van den Bossche et al 2006). It is of interest that resident tissue macrophages, PMNs, and lining layer thickness, did correlate with global disease activity in adult SpA, and that changes in expression of synovial macrophage subsets, PMNs, and MMP-3 clearly reflected response to treatment (Kruithof, De Rycke et al 2006). …”

Relative Expression of Soluble tnf Versus Transmembrane tnf in Spondyloarthritis

“…However, it is as yet unclear in how far these differences contribute to human pathology. [8][9][10] As indicated, TACE (ADAM17, CD156b or EC 3.4.24) is the enzyme responsible for limited proteolysis of tmTNF at Ala76 and Val77, leading to the shedding of sTNF. TACE is a type I transmembrane protein which belongs to a disintegrin and metalloproteinase domain (ADAM) family, which in turn belongs to metzincin super-family.…”