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Evaluation of sublining macrophages by synovial needle biopsy, CD68 immunohistochemistry, and digital image analysis may help to establish evidence based treatments in RA.
Despite decades of research, the aetiology of rheumatoid arthritis (RA) is still unknown. Early theories about its pathogenesis focused on autoantibodies and immune complexes, T cell mediated antigen-specific responses, a T cell independent cytokine network, and aggressive tumour-like behaviour of rheumatoid synovial tissue.1 Recently, B cell targeting approaches underline again the role of autoantibodies. None of these concepts alone could explain the chronic inflammation and progressive joint destruction characteristic of RA.
However, knowledge about the pathophysiological interplay of lymphocytes, macrophages, and local synovial fibroblasts within the synovial membrane has advanced over recent years. The success of treatments targeting tumour necrosis factor α (TNFα) and interleukin (IL) 1 suggest a key role for the monocyte-macrophage system in the pathophysiology of the disease. This is further supported by the fact, that macrophages are abundant within the rheumatoid synovial tissue.2 Moreover, both blood monocytes and tissue macrophages are activated and, in addition to IL1 and TNFα, produce various cytokines, chemokines, and metalloproteinases intimately linked to inflammation and joint destruction.3–5 The significant association between tissue macrophages and radiological progression of the disease6 also points towards an important pathophysiological function. Last but not least, several groups have demonstrated a remarkable reduction in the number of synovial macrophages after antirheumatic treatment.7,8,9,10 It is very likely that various pathogenetic mechanisms result in a final common pathway reflected by activation of synovial macrophages.
In this issue of the Annals Haringman et al examine the effect of antirheumatic treatments on tissue macrophages.11 They combined serial needle biopsies with standardised immunohistological digital image analysis before and after treatment either with disease modifying antirheumatic drugs (DMARDs), biological agents, …
Footnotes
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↵* “The needle and the damage done”. Lyric by Neil Young, Harvest, 1972 (I’ve seen the needle and the damage done, a little part of it in everyone).