ICOS gene haplotypes correlate with IL10 secretion and multiple sclerosis evolution

6 páginas, 2 figuras, 3 tablas -- PAGS nros. 193-198
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
This work was partially supported by Telethon grant E1170 (Rome), FISM grant 2005/R/10 (Genoa), AIRC (Milan), PRIN Project (MIUR, Rome), Fondazione Cariplo (Milan), Compagnia di San Paolo (Turin), Fondazione Cassa di Risparmio di Cuneo (Cuneo), Regione Piemonte (Turin), and Associazione “Amici di Jean” (Turin)