Multiple Sclerosis Stems from Immune System, Not Nervous System

The genetic starting point for autoimmune diseases like multiple sclerosis (MS) and type 1 diabetes may be TK, according to a study published in Nature on October 29, 2014.

A multifaceted team of researchers developed a new mathematical formula to scour existing DNA databases in order to determine why inherited DNA variations contribute to disease. The sequencing techniques they developed examined epigenetic characteristics of specialized immune cells. Previously, the researchers had used a similar tool to study 21 different autoimmune diseases, and they were able to apply that method to the current project.

The researchers probed 39 genome-wide association studies (GWAS) — which each enlist thousands of participants – to identify DNA blocks implicated in genetic factors for diseases. GWAS rarely point to altered proteins, however. The researchers believe this is because only a few protein-encoding gene variants with these DNA codes have been investigated, let alone associated with autoimmune disease.

Investigators found the presence of specific gene variants differ among autoimmune diseases, which can further alter the functional ability of the immune system. This remained true even though the genetic variants are not within genes.

The majority of DNA changes related to autoimmune diseases occurred in the section of DNA known as “enhancers.” The enhancers of DNA — which is typically shaped in stringy molecules – allow DNA to fold so the various proteins can interact with each other. The enhancers also allow the bending of DNA to activate switches that can turn on specific genes. The enhancers the researchers identified as essential to DNA interaction had not been previously thought to have any functional role.

“Once again, research is revealing new meaning in the world of DNA once thought of as junk — short, seemingly random DNA sequences that in fact serve meaningful roles in human physiology,” Alex Marson, MD, PhD, the corresponding author for the study, said in a press release.

After combing through data collected about DNA patterns, the researchers determined T helpers, a type of immune cell, may be a response to stimuli that increase the risk of autoimmune diseases. The researchers believe MS therefore stems from the immune system, and not from genetic variants associated with the nervous system.

“This is highly consistent with the new multiple sclerosis treatments that work on the immune system, suggesting that we finally have a good handle as to the underlying causes of MS,” David A. Hafler, MD, co-first author of the study, continued in the press release. He went on to explain that the immune system plays a primary role in MS, and is almost certainly an autoimmune disease.

The researchers hope these findings can ultimately lead to better diagnosis and improved treatments.