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Updated: Jun 10, 2026

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
09:32

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis

Published on: October 15, 2021

Two HLA class I genes independently associated with multiple sclerosis

Jenny Link1, Aslaug R Lorentzen, Ingrid Kockum

  • 1Karolinska Institutet, Department of Clinical Neuroscience, CMM L8:00, SE-17176 Stockholm, Sweden. jenny.link@ki.se

Journal of Neuroimmunology
|August 4, 2010
PubMed
Abstract

Insights

Human leukocyte antigen (HLA) class I genes influence multiple sclerosis (MS) risk. This study identified specific HLA-A and HLA-C alleles impacting MS susceptibility, offering new insights into the disease

Area of Science:

  • Immunogenetics
  • Neuroimmunology
  • Human Genetics

Background:

  • The human leukocyte antigen (HLA) system plays a critical role in immune response and is implicated in autoimmune diseases like multiple sclerosis (MS).
  • While HLA-DRB1 is a known risk factor for MS, the specific contributions of HLA class I alleles remain incompletely understood.
  • Previous research suggested potential protective roles for HLA-A*02 and HLA-C*05 in MS susceptibility.

Purpose of the Study:

  • To comprehensively investigate the role of HLA class I alleles in modulating the risk of multiple sclerosis (MS).
  • To identify specific HLA class I alleles associated with MS susceptibility or protection.
  • To elucidate the independent contributions of different HLA genes within the class I region.

Main Methods:

  • Genotyping of HLA-DRB1, HLA-A, and HLA-C alleles was performed in a cohort of 1529 MS patients and 1814 controls from Sweden and Norway.
  • Logistic regression analysis was employed for simultaneous assessment of all alleles.
  • Statistical models were adjusted for potential confounding factors to ensure robust findings.

Main Results:

  • Independent genetic effects were observed for HLA-DRB1, HLA-A, and HLA-C genes.
  • The previously reported protective association of HLA-A*02 was confirmed (Odds Ratio [OR]=0.73, p=9.2 x 10⁻⁴).
  • A novel association was identified for HLA-C*08, indicating an increased risk of MS (OR=1.85, p=0.0093).

Conclusions:

  • The HLA class I region harbors at least two distinct genetic factors that influence MS risk.
  • These factors are characterized by independent associations with specific alleles of the HLA-A and HLA-C genes.
  • The findings highlight the complex genetic architecture of MS susceptibility within the HLA locus.

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