Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy |
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Authors: | Email author" target="_blank">Dominique?BaetenEmail author Elli?Kruithof Leen?De Rycke Anemieke?M?Boots Herman?Mielants Eric?M?Veys Filip?De Keyser |
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Institution: | (1) Department of Rheumatology, Ghent University Hospital, Ghent, Belgium;(2) Department of Pharmacology, Organon NV, Oss, The Netherlands |
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Abstract: | Considering the relation between synovial inflammation and global disease activity in rheumatoid arthritis (RA) and the distinct
but heterogeneous histology of spondyloarthropathy (SpA) synovitis, the present study analyzed whether histopathological features
of synovium reflect specific phenotypes and/or global disease activity in SpA. Synovial biopsies obtained from 99 SpA and
86 RA patients with active knee synovitis were analyzed for 15 histological and immunohistochemical markers. Correlations
with swollen joint count, serum C-reactive protein concentrations, and erythrocyte sedimentation rate were analyzed using
classical and multiparameter statistics. SpA synovitis was characterized by higher vascularity and infiltration with CD163+ macrophages and polymorphonuclear leukocytes (PMNs) and by lower values for lining-layer hyperplasia, lymphoid aggregates,
CD1a+ cells, intracellular citrullinated proteins, and MHC–HC gp39 complexes than RA synovitis. Unsupervised clustering of the
SpA samples based on synovial features identified two separate clusters that both contained different SpA subtypes but were
significantly differentiated by concentration of C-reactive protein and erythrocyte sedimentation rate. Global disease activity
in SpA correlated significantly with lining-layer hyperplasia as well as with inflammatory infiltration with macrophages,
especially the CD163+ subset, and with PMNs. Accordingly, supervised clustering using these synovial parameters identified a cluster of 20 SpA
patients with significantly higher disease activity, and this finding was confirmed in an independent SpA cohort. However,
multiparameter models based on synovial histopathology were relatively poor predictors of disease activity in individual patients.
In conclusion, these data indicate that inflammatory infiltration of the synovium with CD163+ macrophages and PMNs as well as lining-layer hyperplasia reflect global disease activity in SpA, independently of the SpA
subtype. These data support a prominent role for innate immune cells in SpA synovitis and warrant further evaluation of synovial
histopathology as a surrogate marker in early-phase therapeutic trials in SpA. |
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