title: CD1A and CD1E gene polymorphisms are associated with susceptibility to multiple sclerosis.
abstract: Multiple sclerosis (MS) is thought to be an autoimmune T-cell-mediated disease directed at myelin antigens of the central nervous system. Besides myelin proteins, lipid components of CNS are supposed to play a role as antigens for T cells in MS. CD1 is a family of MHC-like glycoproteins specialized in capturing and presenting a variety of microbial and self lipids and glycolipids to antigen-specific T cells. CD1-restricted T cells specific for gangliosides and sulfatide have been isolated from subjects with MS and in mice with experimental allergic encephalopathy. We genotyped exon 2 of CD1A and CD1E in 205 MS patients and 223 unrelated healthy controls and determined their association with the presence of anti-ganglioside and anti-sulfatide antibodies. CD1E 01-01 is associated with a reduced risk of MS (OR 0.54, p=0.001); CD1A 02-02 (OR 1.99, p=0.012) or CD1E 02-02 (OR 2.45, p=0.000) with an increased risk. The combination of the genotypes CD1A 02-02 and CD1E 02-02 is present in 90.7% of patients but in only 9.4% controls (OR 94.16, p= 0.000). CD1A and CD1E polymorphisms contribute to the polygenic susceptibility to MS. The functional effects of CD1 polymorphisms are unknown, however changes in CD1 alleles may affect numerous immunological functions.
authors.affiliation: Neurocenter of Southern Switzerland, Ospedale Civico, Lugano, Switzerland.
authors.forename: C M
authors.initials: CM
authors.lastname: Caporale
authors.forename: F
authors.initials: F
authors.lastname: Notturno
authors.forename: M
authors.initials: M
authors.lastname: Pace
authors.forename: A
authors.initials: A
authors.lastname: Aureli
authors.forename: V
authors.initials: V
authors.lastname: Di Tommaso
authors.forename: G
authors.initials: G
authors.lastname: De Luca
authors.forename: D
authors.initials: D
authors.lastname: Farina
authors.forename: A
authors.initials: A
authors.lastname: Giovannini
authors.forename: A
authors.initials: A
authors.lastname: Uncini
mesh_terms: D000328:Adult; D000368:Aged; D018949:Antigens, CD1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; C417738:CD1e antigen