Autoantibodies and chronic pain - Unraveling new mechanisms contributing to pain in rheumatic disease

2026-07-22

Pain is one of the most problematic symptoms of rheumatic disease such as rheumatoid arthritis (RA) and fibromyalgia (FM). We have earlier discovered that antibodies (immunoglobulin, IgG) purified from blood of seropositive rheumatoid arthritis (RA) patients induce pain-like behavior when transferred to mice, independent of inflammatory reactions. Even though FM is not considered an autoimmune disease, it has been suggested that neuroimmune dysregulation contribute to the pathogenesis. Therefore, we purified IgG from FM patients and found that also IgG from FM patients, but not healthy controls, have pronociceptive properties in mice, and surprisingly, bind to satellite glial cells in dorsal root ganglia. Our findings highlights the importance of expanding our view on which chronic pain conditions that could have an underlying autoimmunity as part of the pain pathology. Thus, the overall objective of this project is to investigate both general, and disease specific, pain-inducing mechanisms mediated by RA and FM IgG. Objective 1. Investigate how IgG from RA and FM patients induce pain-like behavior after transfer to mice Objective 2. Search for RA and FM IgG induced maladaptive changes in sensory neurons that mediate hyperexcitability and long-term pain-like behavior Using patient and healthy control samples, in vivo mouse behavioral assays, primary neuronal and non-neuronal cell cultures together with stat-of-the-art methodology, we will investigate how RA and FM-associated autoantibodies alter sensory neuronal excitability. If successful our project will not only challenge the view of how antibodies can contribute to pain but also pin-point specific mechanisms by which disease-relevant antibodies induce and maintain pain independent of previously described inflammatory mechanisms. Such findings promise to resolve currently unanswered questions concerning symptoms of pain in RA and FM, and to pave the way for the development of new pain-relieving therapies.

Sweden

2025-10-15