Multiple sclerosis

HLA-DRB1*15:01

Multiple sclerosis is an inflammatory disease of the central nervous system. The largest genetic contribution comes from HLA-DRB1*15:01. Together with a past Epstein-Barr virus infection, the strongest known environmental factor, this yields a model of predisposition plus trigger.

Predisposition meets trigger

DRB1*15:01 changes which peptides are presented to T cells and favours autoreactive responses against components of the myelin sheath. A large longitudinal study showed that practically all MS cases had a preceding EBV infection. Molecular mimicry between EBV proteins and self structures is a discussed mechanism.

Context

DRB1*15:01 is common and raises risk only moderately; the vast majority of carriers never fall ill. The marker explains predisposition, not course. Genome presents the HLA type as technical evidence and points to the EBV context, without diagnostic claim.

What Genome measures. Presence of the risk allele HLA-DRB1*15:01 and of protective class I types (such as HLA-A*02:01) in the HLA typing.

Related topics

HLA and autoimmunityEBV sequence tracesHLA typing

Sources

  1. 1International MS Genetics Consortium, 2019 Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science 365:eaav7188. doi.org/10.1126/science.aav7188
  2. 2Bjornevik et al., 2022 Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 375:296–301. doi.org/10.1126/science.abj8222