title: ICOS gene haplotypes correlate with IL10 secretion and multiple sclerosis evolution.
abstract: Human ICOS is a T cell costimulatory molecule supporting IL10 secretion. A pilot study investigating variations of the ICOS gene 3'UTR detected 8 polymorphisms forming three haplotypes (A, B, C). Haplotype-A and -C displayed the highest difference. Activated T cells from healthy AA homozygotes expressed significantly less ICOS and secreted more IL10 than AC heterozygotes, whereas AB heterozygotes displayed intermediate levels. Analysis of 441 multiple sclerosis patients and 793 controls showed that frequency of AA homozygosity was significantly lower in MS patients with relapsing-remitting onset (N=416) than in controls (OR=0.70). Moreover, AA patients with relapsing-remitting onset had lower relapse rate and multiple sclerosis severity score than non-AA patients.
authors.affiliation: Interdisciplinary Research Center of Autoimmune Diseases and Department of Medical Sciences, "A. Avogadro" University of Eastern Piedmont, Novara, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Castelli
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Comi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: Stefania
authors.initials: S
authors.lastname: Nicola
authors.forename: Riccardo
authors.initials: R
authors.lastname: Mesturini
authors.forename: Mara
authors.initials: M
authors.lastname: Giordano
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: Elisa
authors.initials: E
authors.lastname: Cerutti
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tesser
authors.forename: Junji
authors.initials: J
authors.lastname: Yagi
authors.forename: José Maria
authors.initials: JM
authors.lastname: Rojo
authors.forename: Franco
authors.initials: F
authors.lastname: Perla
authors.forename: Maurizio
authors.initials: M
authors.lastname: Leone
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Francesco
authors.initials: F
authors.lastname: Monaco
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D016753:Interleukin-10 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D020413:3' Untranslated Regions; D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D016753:Interleukin-10