The Involvement of HLA Class II Alleles in Multiple Sclerosis: A Systematic Review with Meta-analysis

Area of Science:

• Immunogenetics
• Neuroimmunology
• Human Genetics

Background:

• Multiple Sclerosis (MS) is a CNS demyelinating disease with unpredictable progression.
• Genetic factors, particularly Human Leukocyte Antigen (HLA) alleles, confer the highest risk for MS.
• Ethnic variability in HLA alleles necessitates a global analysis of their association with MS.

Purpose of the Study:

• To systematically review and meta-analyze existing literature on the association between MS and HLA class II genes across all ethnicities.
• To summarize the transethnic risk and protective roles of specific HLA class II alleles in MS susceptibility.

Main Methods:

• Systematic search of meta-analyses and systematic reviews concerning MS and HLA associations.
• Inclusion of 5 articles with data from 15,232 MS patients and 24,194 ethnically matched controls.
• Analysis of Human Leukocyte Antigen (HLA) class II gene variants, including DRB1 and DQB1 alleles.

Main Results:

• DRB1*15 and DQB1*06:02 alleles significantly increase MS risk across various ethnic groups (e.g., Caucasians, Chinese, South Americans).
• DRB1*01, DRB1*09, DRB1*11, DRB1*12, and DRB1*16 alleles demonstrate a protective effect against MS.
• The DQB1*06:02 risk allele is implicated in MS-like disease in humanized mice, mediated by autoimmune responses to myelin peptides.

Conclusions:

• Both DQB1 and DRB1 gene variants play crucial, and potentially equal, roles in MS susceptibility and protection globally.
• Understanding HLA class II associations provides insights into MS pathogenesis and potential therapeutic targets.
• The specific amino acid residues within HLA molecules influence peptide binding and autoimmune responses in MS.