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bioRxiv · 10.64898/2026.02.11.703666

Elimination of intramuscular immunoglobulin accumulation alleviates Duchenne Muscular Dystrophy

Chang, X.·Chen, Y.·Zhang, L.·Guo, W.·Huang, M.·Liang, Z.·Zhu, E.·Li, G.·Qi, T.·Chang, C.·Guo, X.·Sun, W.·Li, J.·Liu, J.·Qiu, H.·Zhu, L.·Liu, Y.·Chen, J.·Ren, S.·Bai, R.·Wang, J.·Gao, Y.·Song, Y.·Li, F.·Dai, Y.·Wu, Z.·Hu, J.·Ji, W.
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Abstract

Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disorder due to loss of dystrophin, a cytoskeletal protein critical for muscle integrity and functionality. Despite recent therapeutic advances, there remains a significant unmet need for more effective and accessible therapeutics. Here, we discovered an early accumulation of immunoglobulin G (IgG) in the sarcolemma, which exacerbates tissue inflammation and disease progression. The IgG accumulation primarily resulted from ectopic localization of Fc{gamma}R1, a high-affinity IgG Fc receptor, on dystrophin-deficient myofibers. In two independent murine models, eliminating IgG accumulation via B cell depletion provided sustained benefit to alleviate DMD progression. Our findings uncover a novel disease accelerator in DMD and demonstrate the potential to target this mechanism as therapeutics for broader population of patients with DMD.

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Chang, X., Chen, Y., Zhang, L., Guo, W., Huang, M., Liang, Z., Zhu, E., Li, G., Qi, T., Chang, C., Guo, X., Sun, W., Li, J., Liu, J., Qiu, H., Zhu, L., Liu, Y., Chen, J., Ren, S., Bai, R., Wang, J., Gao, Y., Song, Y., Li, F., Dai, Y., Wu, Z., Hu, J., Ji, W.. 2026-02-12. Elimination of intramuscular immunoglobulin accumulation alleviates Duchenne Muscular Dystrophy. https://doi.org/10.64898/2026.02.11.703666

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