ICOS gene haplotypes correlate with IL10 secretion and multiple sclerosis evolution.
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.
Castelli
Luca
L
Interdisciplinary Research Center of Autoimmune Diseases and Department of Medical Sciences, "A. Avogadro" University of Eastern Piedmont, Novara, Italy.
Comi
Cristoforo
C
Chiocchetti
Annalisa
A
Nicola
Stefania
S
Mesturini
Riccardo
R
Giordano
Mara
M
D'Alfonso
Sandra
S
Cerutti
Elisa
E
Galimberti
Daniela
D
Fenoglio
Chiara
C
Tesser
Fabiana
F
Yagi
Junji
J
Rojo
José Maria
JM
Perla
Franco
F
Leone
Maurizio
M
Scarpini
Elio
E
Monaco
Francesco
F
Dianzani
Umberto
U
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
D020413:3' Untranslated Regions; D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D016753:Interleukin-10