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: Luca Castelli, Cristoforo Comi, Annalisa Chiocchetti, Stefania Nicola, Riccardo Mesturini, Mara Giordano, Sandra D'Alfonso, Elisa Cerutti, Daniela Galimberti, Chiara Fenoglio, Fabiana Tesser, Junji Yagi, José Maria Rojo, Franco Perla, Maurizio Leone, Elio Scarpini, Francesco Monaco, Umberto Dianzani
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 186 Issue 1-2 Pg. 193-8 (May 2007) ISSN: 0165-5728 [Print] Netherlands
• PMID: 17481737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• Antigens, Differentiation, T-Lymphocyte
• ICOS protein, human
• Inducible T-Cell Co-Stimulator Protein
• Interleukin-10

Topics

• 3' Untranslated Regions (genetics)
• Antigens, Differentiation, T-Lymphocyte (genetics)
• Case-Control Studies
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Haplotypes (genetics)
• Humans
• Inducible T-Cell Co-Stimulator Protein
• Interleukin-10 (metabolism)
• Leukocytes, Mononuclear (metabolism)
• Linkage Disequilibrium
• Male
• Multiple Sclerosis (genetics, metabolism)
• Statistics, Nonparametric