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<p>Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system. B cell depleting treatments are effective MS therapies, and while antibodies may serve as a biomarker, little is known about how they participate in MS pathology. Using a proteolipid protein 1 complex-specific (PLP1c) recombinant antibody cloned from cerebrospinal fluid plasmablasts of MS patients, we studied the development and resolution of antibody-mediated demyelinating lesions in vivo in mice. Demyelination was complement-dependent and resolved over four weeks. Because of the previously described impact of microglia on remyelination, we targeted microglia depletion with CSF1R inhibition to test their role in this model. Despite a significant reduction in total microglia following CSF1R inhibition, microglia or macrophage density was high in recovering lesions. Premyelinating oligodendrocyte populations were altered without impacting gross lesion recovery. Future work will determine if PLP1c-binding antibodies are representative of other MS-derived antibodies, and how pathogenic MS autoantibodies may contribute to the variability of MS lesion remyelination.</p>

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CSF1R inhibition following antibody mediated demyelination has limited impact on remyelination

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月9日

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  • Lisa C. Golden,
  • Graham C. Peet,
  • Rebecca E. Rodriguez,
  • Nicholas J. Jahahn,
  • Gregory P. Owens,
  • Jeffrey L. Bennett,
  • Wendy B. Macklin

摘要

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system. B cell depleting treatments are effective MS therapies, and while antibodies may serve as a biomarker, little is known about how they participate in MS pathology. Using a proteolipid protein 1 complex-specific (PLP1c) recombinant antibody cloned from cerebrospinal fluid plasmablasts of MS patients, we studied the development and resolution of antibody-mediated demyelinating lesions in vivo in mice. Demyelination was complement-dependent and resolved over four weeks. Because of the previously described impact of microglia on remyelination, we targeted microglia depletion with CSF1R inhibition to test their role in this model. Despite a significant reduction in total microglia following CSF1R inhibition, microglia or macrophage density was high in recovering lesions. Premyelinating oligodendrocyte populations were altered without impacting gross lesion recovery. Future work will determine if PLP1c-binding antibodies are representative of other MS-derived antibodies, and how pathogenic MS autoantibodies may contribute to the variability of MS lesion remyelination.