Multiple Sclerosis: Microglia, Monocytes, and Macrophage-Mediated Demyelination

• Published in: Journal of neuropathology and experimental neurology Vol. 80; no. 10; pp. 975 - 996
• Main Authors: Prineas, John W, Parratt, John D E
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.10.2021
• Subjects: Adolescent; Adult; Aged; Apoptosis; Blood vessels; Demyelinating diseases; Demyelinating Diseases - pathology; Development and progression; Female; Health aspects; Humans; Immunoglobulin G; Macrophages; Macrophages - pathology; Macrophages - ultrastructure; Male; Microglia - pathology; Microglia - ultrastructure; Middle Aged; Monocytes; Monocytes - pathology; Monocytes - ultrastructure; Multiple sclerosis; Multiple Sclerosis - pathology; Original; Young Adult; Australia; United Kingdom; Subpial demyelination; Oligodendrocyte apoptosis; Myeloid cells; Secondary progressive MS; Acute multiple sclerosis; Antibody-dependent cellular phagocytosis; Monocyte encephalopathy
• ISSN: 0022-3069; 1554-6578; 1554-6578
• DOI: 10.1093/jnen/nlab083

Abstract This study examined the roles of microglia and monocytes in myelin destruction in patients with early multiple sclerosis (MS). Twenty-two cases were studied; the clinical duration was <9 weeks in 10 cases. Twenty myeloid cell subtypes or categories were identified including 2 cell types not known previously to occur in demyelinating diseases. Commencing myelin breakdown in plaques and in perivascular and subpial tissues occurred in the immediate presence of infiltrating monocytes and was effected by a homogeneous population of IgG-positive Fc receptor-bearing early phagocytes interacting with abnormal myelin. Oligodendrocyte apoptosis was observed in intact myelinated tissue bordering areas of active demyelination. Capillaries in the cerebral cortex plugged by large numbers of monocytes were common in acute cases of MS and in a patient with a neuromyelitis optica variant and extreme systemic recruitment of monocytes. In an MS patient with progressive disease, microglial nodules centered on MHC-II-positive capillaries plugged by monocytes were present in the cerebral cortex. This constitutes a new gray matter lesion in MS.