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IGHG4 Expression in C2 Human Dorsal Root Ganglion Potentially Links B Cells to Spreading Chronic Neck Pain

Mancilla Moreno, M.; Payne, C.; Mazhar, K.; Arendt-Tranholm, A.; Yap, N.; Chiu, A. P.; Wilde, M. A.; Patel, P. J.; Yousuf, M. S.; Tavares Ferreira, D.; Jarvik, J. G.; Turner, J. A.; Grace, P. M.; Hofstetter, C. P.; Price, T. J.; Curatolo, M.

2024-11-17 pain medicine
10.1101/2024.11.12.24317004 medRxiv
Show abstract

Very little is known about the molecular mechanisms underlying chronic neck pain, a highly prevalent and burdensome condition. We analyzed the C2 dorsal root ganglion (DRG) of patients with neck pain who underwent C1-2 arthrodesis surgery. Using spatial transcriptomics, we provide the first report of IGHG4 expression in a human DRG. IGHG4 encodes immunoglobulin G4 (IgG4). Infiltration of IgG4-producing lymphocytes characterizes IgG4-related disease, an immune-mediated inflammatory condition, and IgG4 autoantibodies sensitize DRG sensory neurons. The expression was found only in one of the 8 patients analyzed, was very high, and co-localized with B cells, which have a crucial role in IgG4 production. The findings uncover a molecular mechanism potentially involved in chronic neck pain in patients susceptible to infiltration of IgG4-producing B cells.

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