A genetic basis for the severity of multiple sclerosis

Multiple sclerosis is an autoimmune, neurodegenerative disorder with highly variable long-term outcomes. 1 Jokubaitis VG Campagna MP Ibrahim O et al. Not all roads lead to the immune system: the genetic basis of multiple sclerosis severity. Brain. 2023; 146: 2316-2331 Crossref PubMed Scopus (5) Google Scholar More than 200 common autosomal variants have been associated with the risk of developing multiple sclerosis. 2 International Multiple Sclerosis Genetics ConsortiumMultiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019; 365eaav7188 Crossref Scopus (572) Google Scholar These established risk variants map almost exclusively to genes expressed by peripheral immune cells and CNS-resident microglia. Immunomodulatory disease-modifying therapies target lymphocytes, and particularly B cells, to prevent clinical and radiological inflammatory activity. 3 De Angelis F John NA Brownlee WJ Disease-modifying therapies for multiple sclerosis. BMJ. 2018; 363k4674 Google Scholar However, despite the availability of these therapies, insidious neurological disability continues to accumulate in some patients. 4 Brown JWL Coles A Horakova D et al. Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA. 2019; 321: 175-187 Crossref PubMed Scopus (283) Google Scholar