The following is a summary of “Synovial innate immune exhaustion is associated with worse pain in knee osteoarthritis,” published in the December 2024 issue of Rheumatology by Philpott et al. 

Uncontrolled pain in knee osteoarthritis (OA) remains a major challenge. Synovial innate immune cell infiltration (synovitis) is linked to worse pain, but the role of immune regulatory cells is unclear. 

Researchers conducted a retrospective study to identify synovial innate immune cell subsets and mechanisms linked to worse pain in knee OA.  

They examined synovial tissue biopsies from 122 patients with knee OA pain (Knee injury and OA Outcome Score; KOOS) to investigate links between histopathology and pain severity. They used spatial transcriptomics and proteomics to synovial tissue microenvironments (n=32) and conducted single-cell RNA sequencing (n=8) to characterize synovial cell composition and communication networks in patients with more severe pain. 

The results showed that synovial microvascular dysfunction and perivascular edema were associated with worse KOOS pain (-10.76 [95%CI -18.90, -2.61]). Patients with more pain had fewer immune-regulatory macrophages, expanded fibroblast subsets, and heightened neurovascular remodeling pathways. Synovial macrophages from these patients displayed immune exhaustion, decreased phagocytic function (-19.42% [95%CI -35.96, -2.89]), and their conditioned media-induced neuronal cell stress in the dorsal root ganglia. 

Investigators found that exhaustion, dysfunction, and loss of immune-regulatory macrophages were linked to worse pain in OA. These factors may represent important therapeutic targets for managing knee OA pain. 

Source: acrjournals.onlinelibrary.wiley.com/doi/abs/10.1002/art.43089