The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody

Abstract

We sought to define the pathological features of myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) in an archival autopsy/biopsy cohort. We histopathologically analyzed 2 autopsies and 22 brain biopsies from patients with CNS inflammatory demyelinating diseases seropositive for MOG-antibody by live-cell-based-assay with full length MOG in its conformational form. MOGAD autopsies (ages 52 and 67) demonstrate the full spectrum of histopathological features observed within the 22 brain biopsies (median age, 10 years; range, 1-66; 56% female). Clinical, radiologic, and laboratory characteristics and course (78% relapsing) are consistent with MOGAD. MOGAD pathology is dominated by coexistence of both perivenous and confluent white matter demyelination, with an over-representation of intracortical demyelinated lesions compared to typical MS. Radially expanding confluent slowly expanding smoldering lesions in the white matter as seen in MS, are not present. A CD4+ T-cell dominated inflammatory reaction with granulocytic infiltration predominates. Complement deposition is present in all active white matter lesions, but a preferential loss of MOG is not observed. AQP4 is preserved, with absence of dystrophic astrocytes, and variable oligodendrocyte and axonal destruction. MOGAD is pathologically distinguished from AQP4-IgG seropositive NMOSD, but shares some overlapping features with both MS and ADEM, suggesting a transitional pathology. Complement deposition in the absence of selective MOG protein loss suggest humoral mechanisms are involved, however argue against endocytic internalization of the MOG antigen. Parallels with MOG-EAE suggest MOG may be an amplification factor that augments CNS demyelination, possibly via complement mediated destruction of myelin or ADCC phagocytosis.

Role of B Cells in Multiple Sclerosis and Related Disorders

“…62,63 Typical MS cases are largely anti-MOG negative. 64,65 In a small trial, initial detection of serum anti-MOG and anti-myelin basic protein antibodies has been shown to be correlated with early conversion from clinically isolated syndrome to definite MS. 66 Analysis of pathogenic antibodies could thereby be of value to estimate individual risk of early relapse. However, the association between anti-MOG antibodies and progression to MS has not been reproduced in other trials.…”

Recent developments in MOG-IgG associated neurological disorders

“…The pathological features of MOG-IgG associated disorders were recently analysed in a larger series of two autopsies and 22 brain biopsies from patients with CNS inflammatory demyelinating diseases. 141 Both autopsies and the 22 brain biopsies had similar clinical, radiologic, laboratory and histopathological features. Pathology was dominated by the coexistence of both perivenous and confluent white matter demyelination, with an over-representation of intracortical demyelinated lesions compared with typical MS.…”

Aquaporin-4- und Myelin-Oligodendrozyten-Glykoprotein-Antikörper-assoziierte Optikusneuritis: Diagnose und Therapie

“…Histopathologisch sind Läsionen bei Patienten mit MOG-EM vornehmlich durch einen Verlust der Myelinscheiden und (meist) Komplementablagerungen gekennzeichnet. Als distinktes Merkmal findet sich, anders als bei MS, zusätzlich eine außerhalb der Läsionen nachweisbare perivaskuläre Demyelinisierung [45,46].…”