Multiple sclerosis and the CTLA4 autoimmunity polymorphism CT60: no association in patients from Germany, Hungary and Poland

Abstract

Polymorphisms in the CTLA4 gene region have been associated with susceptibility to autoimmune diseases. The recently described single nucleotide polymorphism CT60, located in the 3' untranslated region of CTLA4 is associated with Graves' disease, thyroiditis, autoimmune diabetes and other autoimmune diseases. A case-control association study was conducted in German, Hungarian and Polish multiple sclerosis (MS) patients and regional control individuals for the CTLA4 CT60 and +49A/G polymorphisms. No significant association of these polymorphisms or respective haplotypes with MS was found. No association of CT60 genotypes with T cell expression of ICOS and CTLA-4 after in vitro stimulation was detected.

Polymorphisms in CD28, CTLA-4, CD80 and CD86 genes may influence the risk of multiple sclerosis and its age of onset

“…However the results of these investigations are inconsistent and ambiguous. Some of them did not show the influence of CTLA-4 on MS (Dyment et al, 2002, Greve et al, 2008, Roxburgh et al , 2006. On the contrary, the results of other studies reported the association of this gene with multiple sclerosis susceptibility (Harbo et al, 1999, Kantarci et al, 2003, Ligers et al, 1999.…”

Involvement of Immune Regulation in Multiple Sclerosis

“…The B7 molecules, CD80 and CD86, interact with receptors found on DCs and when the balance of these interacting proteins is off, exacerbated symptoms of MS often develop. Although it has been suggested that CTLA-4 serves a protective role in the brain that leads to MS once inhibited, 123,124 there is conflicting research regarding this, 133,134 calling for additional study to determine the true nature of this relationship. There has also been a lack of consistency in the effects of CTLA-4 polymorphisms on varying cohorts, [131][132][133][134] which indicates a possible ethnic relationship between MS and variations in CTLA-4.…”

“…120 In contrast, studies performed using Italian, Japanese, Iranian, German, Hungarian, and Polish cohorts were unable to conclude that there was an association between CTLA-4 polymorphisms and MS in their patients. [131][132][133][134] It should be noted that the sample sizes for some of these studies were small. Based on the differing groups in which a connection between CTLA-4 and MS was observed, the association is perhaps indicative of an ethnic component, which requires further investigation to elucidate the true nature of the relationship.…”

Futility of the autoimmune orthodoxy in multiple sclerosis research

“…While ADEM and EAE are comparable disorders, MS is shown to be a different disease. This is further attested to by the failure of large epidemiological studies to show an association between MS and other autoimmune disorders [5].…”