title: Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.
abstract: In some Caucasian populations, multiple sclerosis (MS) susceptibility has been independently related to given alleles of HLA or Gm systems that respectively code for major histocompatibility complex class I and II antigens or immunoglobulin G heavy chains. Whether given combinations of alleles at both series of loci simultaneously influence MS susceptibility and/or severity was investigated by comparing 147 French MS patients and 226 geographically-matched healthy controls. The G2m(-23)/HLA-B35 phenotype and G1m(-1)/HLA-B7(-)/HLA-DR2 phenotype were respectively associated with significant protection against (relative risk = 0.05) and susceptibility to (relative risk = 4.3) MS. When considering MS severity, the presence of HLA-B7 antigen correlated with a more severe disease in Gm1/Gm3 heterozygous patients, but not in Gm3/Gm3 homozygous patients. Conversely, an HLA-B12-associated milder disease was restricted to Gm3/Gm3 homozygotes. These results demonstrate the combined influence on MS of genetic loci that are unlinked but immune response-associated. Combined Gm and HLA typing is very likely able to serve as a prognostic indicator in this disease.
authors.forename: J P
authors.initials: JP
authors.lastname: Salier
authors.forename: R
authors.initials: R
authors.lastname: Sesboüé
authors.forename: C
authors.initials: C
authors.lastname: Martin-Mondière
authors.forename: M
authors.initials: M
authors.lastname: Daveau
authors.forename: P
authors.initials: P
authors.lastname: Cesaro
authors.forename: B
authors.initials: B
authors.lastname: Cavelier
authors.forename: A
authors.initials: A
authors.lastname: Coquerel
authors.forename: L
authors.initials: L
authors.lastname: Legrand
authors.forename: J M
authors.initials: JM
authors.lastname: Goust
authors.forename: J D
authors.initials: JD
authors.lastname: Degos
mesh_terms: D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000235:genetics*; D007074:Immunoglobulin G / Q000235:genetics*; D008297:Male; D009103:Multiple Sclerosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D012306:Risk
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G