Immunopathology of multiple sclerosis

Abstract

Two decades of clinical experience with immunomodulatory treatments for multiple sclerosis point to distinct immunological pathways that drive disease relapses and progression. In light of this, we discuss our current understanding of multiple sclerosis immunopathology, evaluate long-standing hypotheses regarding the role of the immune system in the disease and delineate key questions that are still unanswered. Recent and anticipated advances in the field of immunology, and the increasing recognition of inflammation as an important component of neurodegeneration, are shaping our conceptualization of disease pathophysiology, and we explore the potential implications for improved healthcare provision to patients in the future.

Genome‐wide association studies of multiple sclerosis

“…Since then, a great deal of effort has been expended to better characterise these associations both genetically and functionally, although we still do not understand how changes to antigen display increase risk for MS or any other autoimmune disease 47. One of the main challenges to interrogating the MHC is the complexity of the region: multiple alleles in the region are under both positive and balancing natural selection in different populations, leading to complex long‐range haplotype structures, and many of the genes in the classical regions also show high‐sequence homology.…”

Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

“…Multiple sclerosis is a central nervous system disease characterized by a complex pathophysiology,1 the fundamental features of which have been derived from the analysis of post mortem tissue 2, 3, 4, 5. Spinal cord pathology is an important determinant of permanent neurological disability with cardinal characteristics being inflammatory demyelination, synaptic, neuronal and axonal loss 6, 7, 8, 9, 10, 11.…”

G1m1 predominance of intrathecal virus‐specific antibodies in multiple sclerosis

“…B cells can present antigens to T cells, undergo affinity maturation and clonal expansion, and differentiate into antibody‐secreting cells 2. In a majority of MS patients, antibody‐secreting cells are present in the central nervous system, and locally produced immunoglobulin G (IgG) can be detected in the cerebrospinal fluid (CSF) as oligoclonal bands (OCB) 3.…”