Natural Variations in Interleukin-16 Gene Linked to MS Risk in Small Study

Small natural variations within the DNA sequence of the gene for interleukin-16 (IL-16) were linked to an increased susceptibility to multiple sclerosis (MS) in a small group of Iranian patients.

The study, “The Association of Interleukin-16 Gene Polymorphisms with IL-16 Serum Levels and Risk of Multiple Sclerosis,” was published in the journal Immunological Investigations.

IL-16 is secreted by several different immune cells, and is one of the most potent pro-inflammatory cytokines, or signaling molecules that have a specific effect on immune cell interaction and communication, and which stimulate the movement of cells toward inflammation sites.

“There are several lines of evidence including increased IL-16 levels in the spleen, lymph nodes, brain, and microglia in experimental autoimmune encephalomyelitis (EAE) mice [a mouse model of MS] and also its correlation with severity of disease, inflammation, as well as the extent of axonal damage that suggest the involvement of IL-16 in the pathogenesis of MS,” the researchers wrote.

Small variations, called single-nucleotide polymorphisms (SNPs), in the gene coding for IL-16 may alter this cytokine function and deregulate its expression. However, whether SNPs in the IL-16 gene affect a person’s susceptibility to MS is not established.

To test this hypothesis, researchers investigated the link between different SNPs and IL-16 levels in blood samples from relapsing-remitting multiple sclerosis (RRMS) patients and healthy controls in an Iranian population. In total, they analyzed 250 MS patients and 400 controls. Researchers chose three specific SNPs, called rs4072111, rs4778889, and rs11556218, all with a previously established tie to other autoimmune diseases, such as systemic lupus erythematosus.

Researchers found “that the rs4072111C/T and rs11556218T/G polymorphisms of IL16 gene and the serum levels of IL-16 were significantly associated with the susceptibility to MS.” Moreover, they observed that higher blood levels of IL-16 also correlated with disease severity in this Iranian population of patients. Similar results were previously reported in a Chinese MS patient group.

These results show, for a first time in an Iranian population, a link between IL-16 gene polymorphisms and MS risk, via increasing the levels of IL-16 in patients’ blood.

“However, further studies in different populations are needed to establish these polymorphisms as markers for genetic susceptibility to MS,” the researchers concluded.