While Myeloid cells are abundant in lupus arthritis (LA) and rheumatoid arthritis (RA), based on clinical presentation LA and RA are considered distinct diseases. Although inflammatory arthritis is common in patients with lupus, the pivotal mechanisms leading to joint damage have not been investigated. We tested the hypothesis that IL-34, but not CSF-1, is a predictive biomarker that is integral in perpetuating synovial destructive inflammation in both LA and RA. We report the novel findings that:
using longitudinally tracked patients, IL–34, not CSF–1, is a clinical predictive biomarker for both LA and RA; and
IL–34 is more robustly expressed in the synovial tissue, cells and fluid compared to CSF–1 in both LA and RA.
Probing into the IL-34 dependent mechanisms in vitro we find that:
IL–34 promotes synovial hyperplasia more robustly than CSF–1, and increases chemokines that recruit neutrophils and monocytes (Mo) into the synovium in LA and RA;
Mo and neutrophils stimulated by IL–34, via cell contact and/or released mediators, such as ROS, destroy synovial cells;
signalling via the two IL–34 receptors, cFMS and protein–tyrosine phosphatase (PTPRZ), promote IL–34 and CSF–1 mediated synovial cell hyperplasia and cytotoxicity.
Taken together, IL-34-dependent mechanisms are pivotal and similar in mediating LA and RA. Moreover, tracking serum IL-34 is a reliable biomarker for managing the individualised treatment of patients with both LA and RA.
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