As we are rapidly learning, autoimmune diseases appear to be a result of an unclear combination of genetics, environment and immune regulatory problems. While we don’t completely understand the contribution of each in terms of proportions and impact, researchers have been somewhat successful in starting to put the pieces of the genetic puzzle together. (This is also occurring regarding environmental impacts, though this is beyond the scope of this article.) Here we take a look at some of the important genetic findings studies have yielded in terms of how our DNA contributes to the emergence of autoimmune disease.
This is a tough question to answer except to say that genes definitely seem to play a major role in this regard. This is evidenced by the sheer number of gene locations that have been linked in some way to autoimmune disorders. This genetic table on Eupedia.com offers a list of genes connected to individual autoimmune conditions, which you might find helpful.
As with so many other disorders in medicine, the exact nature of genetic influence and how much it accounts for in terms of disease formation is presently still very much a mystery. But, that mystery does seem to be unfolding slowly. It does appear thus far that a combination of genes and environment is required for these diseases to manifest. Beyond that, we are still working out the particulars.
For an overview of our current understanding of genetic factors in autoimmune disease, this page from the NIH covers the topic quite well. It’s clear from these and other sources that autoimmune conditions are most certainly inheritable (though not always passed on and/or activated) – confirmed through twin studies and clinical observation within families. Researchers have also discovered that while some genes promote development of disease, others serve protective functions.
The HLA (Human Leukocyte Antigen) genes are the human version of a gene group found more widely in nature, called the MHC (Major Histocompatibility Complex), which reside on chromosome 6 and code for something called cell surface proteins.
As it sounds, these are proteins that reside on the outside of a cell, and which can therefore function as antigens or present antigens to the immune system for assessment. In those affected by one or more of the HLA genes, the body may not recognize the corresponding proteins (or the antigens they present) as native, which of course stimulates an autoimmune response.
The HLA gene family (known as “loci”, for their locations on chromosome 6) has been extensively studied in terms of their relationship to autoimmune conditions. Classified into three MHC groups, class II appears to have the most impact on autoimmune conditions. Though our understanding of this group of genes still leaves us short of being able to develop effective treatments at the moment (at least clinically, for the most part), the ongoing research and impressive rate of discovery leaves us with great hope for the near future.
Some common examples of HLA genes that have been correlated with and implicated in autoimmune disease include:
As with the HLA family above, the IL genes code for a group of proteins known as “interleukins” which are a type of “cytokine”. (I mention these terms because many with autoimmune conditions may be familiar with them. Other cytokines that you may have heard of include tumor necrosis factor (TNF) and the interferons.)
These proteins are inflammatory mediators (among other things) that act as messengers within the body and cells, promoting and regulating our immune responses. When they act inappropriately against the self, inflammation of various organs is the result.
Some of the conditions affected by variation in the IL gene family are:
There are dozens if not hundreds of genes and gene families that have been correlated with various autoimmune diseases. While an expansive look at these genes is beyond the purpose of this article, let’s take a quick look at a few of the better-known examples.
Other genes connected to autoimmune diseases include are below, with links to NIH and other academic studies:
This list is of course far from exhaustive and merely provides some examples of other genes that have been discovered and are now being researched for their connections to autoimmune disorders. More information can be found at many of the links provided above.
About the Author
Dr. Rothbard is a professional medical writer and consultant based in New York City, specializing in medical education articles targeted at a variety of audiences, from children through clinicians. After leaving medicine, he worked as a biology and medical science educator for several years, before deciding to pursue writing full-time. He may be reached at [email protected].
This blog post was originally published by AutoimmuneMom.com, written by Dr. Rothbard, and first published on Jul 17, 2014.