IgG Autoantibodies and Fc Signaling: A New Axis of Neuropathic Pain in Endometriosis 2265840

Abstract

Abstract Introduction Endometriosis is a chronic inflammatory disease redefined as a neuroimmune pain syndrome. Pain arises from neuroimmune crosstalk, driving peripheral and central sensitization. Sensory nerves release SP and CGRP, amplifying inflammation and lesion growth. This abstract proposes that B cell—derived IgG autoantibodies trigger neuropathic pain through the FcγR axis, linking neurons, macrophages, and microglia–offering a new immunomodulatory target. Methods Therapeutic strategies target the B cell—FcγR axis to modulate neuroimmune pain in endometriosis. Approaches include B cell depletion with anti-CD20 antibodies, FcγR or BTK inhibition, and blockade of neuropeptides such as CGRP and SP. Additional options include TRPV1 antagonists and NGF/BDNF neutralization to reduce hyperinnervation, inflammation, and neuropathic pain. Results Immunomodulatory and neuro-targeted therapies show promise beyond hormonal treatments. Targeting the B cell—FcγR axis with anti-CD20 antibodies, BTK inhibitors, or FcγR antagonists may reduce cytokine release and IgG-mediated neuropathic pain. Blocking CGRP-RAMP1 signaling lessens hyperalgesia and lesion growth, while TRPV1, NGF, and BDNF inhibition can desensitize nerves and reduce inflammation. Conclusion Endometriosis involves intertwined neuroimmune and inflammatory pathways driving chronic pain. Neurogenic inflammation, hyperinnervation, and immune dysregulation sustain sensitization. B cell—derived IgG autoantibodies acting through the FcγR axis may trigger neuropathic pain and glial activation, linking peripheral inflammation to central sensitization and chronic pelvic pain. Funding Source n/a Topic Categories Neuroimmunology (NEUR)