Differential contribution of immune effector mechanisms to cortical demyelination in multiple sclerosis
Lagumersindez-Denis N, Wrzos C, Mack M, Winkler A, van der Meer F, Reinert MC, Hollasch H, Flach A, Brühl H, Cullen E, Schlumbohm C, Fuchs E, Linington C, Barrantes-Freer A, Metz I, Wegner C, Liebetanz D, Prinz M, Brück W, Stadelmann C, Nessler S.
Acta Neuropathol. online article
Cortical demyelination is a widely recognized hallmark of multiple sclerosis (MS) and correlate of disease progression and cognitive decline. The pathomechanisms initiating and driving gray matter damage are only incompletely understood. Here, we determined the infiltrating leukocyte subpopulations in 26 cortical demyelinated lesions of biopsied MS patients and assessed their contribution to cortical lesion formation in a newly developed mouse model. We find that conformation-specific anti-myelin antibodies contribute to cortical demyelination even in the absence of the classical complement pathway. We conclude that biologics depleting CCR2+ monocytes might be attractive candidates for preventing cortical lesion formation and ameliorating disease progression in MS.
