CTLA4 and primary progressive multiple sclerosis: They found that although there was no differences in the allelic distribution of the G49 allele between the MS patients and the controls, the G49 allele was present in a significantly larger percentage of PPMS patients in comparison to patients with a bout onset of the disease, thus supporting the hypothesis that CTLA-4 mutations could be involved in the pathogenesis of PPMS by affecting the down regulation of T cell function and thus contributing to the low-grade inflammatory process that characterizes PPMS [129].