Differential expression and response to anti‐TNFα treatment of infiltrating versus resident tissue macrophage subsets in autoimmune arthritis

Abstract

Synovial macrophages play a pivotal role in the pathogenesis of chronic autoimmune arthritis by contributing to local inflammation and tissue damage and are therefore a primary target for therapeutic intervention. The aim of the present study was to investigate in more detail the relative contribution of different synovial macrophage subsets with potentially different inflammatory or anti-inflammatory functions by analysing the two most frequent forms of human autoimmune arthritis, spondyloarthropathy (SpA) and rheumatoid arthritis (RA). Both infiltrating macrophages from peripheral blood expressing myeloid-related proteins (MRP) 8 and 14, and resident tissue macrophages expressing CD163 were abundant in inflamed synovium. Whereas the global number of synovial macrophages was similar in both diseases, infiltrating macrophages were increased in the RA lining layer in contrast with resident tissue macrophages, which were more frequently observed in SpA. Soluble MRP8/MRP14 complexes, which were secreted locally in the joint during the infiltration process, were increased in the serum of arthritis patients and, in contrast with soluble CD163 shed from resident tissue macrophages, correlated well with global inflammatory parameters. Treatment in vivo with anti-TNFalpha had a rapid and pronounced effect on the infiltration of MRP-positive macrophages into tissues, as evidenced by histopathological analysis and serum MRP8/MRP14 levels. Taken together, these data support an important role for infiltrating versus resident tissue macrophages in human autoimmune synovitis and indicate that macrophage products such as soluble MRP8/MRP14 complexes are valuable biomarkers for the experimental and clinical monitoring of specific disease mechanisms in vivo.

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

“…In fact, CRP level is an important biomarker of radiographic progression in RA patients receiving DMARDs (methotrexate), but this predictive value disappears when RA patients are treated with TNFi (34). Moreover, calprotectin serum levels significantly decrease after TNFi treatment and are independently associated with radiographic progression in RA (14,17).…”

“…Calprotectin serum levels decrease significantly after TNFi treatment (15), and therefore monitoring of the response to biologic therapy might be useful (16). Infliximab (IFX) significantly decreases calprotectin serum levels in RA patients, which is confirmed by immunohistochemical staining for MRP-8/MRP-14 on serial synovium sections, showing a progressive decrease in the number of infiltrating MRP-14-positive macrophages (17). The results of a recent study suggest that calprotectin could be a predictor of the response to biologic therapy in RA (18).…”

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).…”

The Effect of Class A Scavenger Receptor Deficiency in Bone

“…There are several subpopulations of resident macrophages including perivascular, peritoneal, synovial, intestinal, alveolar, and bone marrow macrophages (11)(12)(13). In bone marrow, hematopoietic stem cells give rise to osteoclasts that are derived from monocyte/macrophage precursors (14 -16).…”