Where genes and environment meet

Autoimmune diseases arise when the body raises an immune response against substances normally present in the body.  In other words, your immune system attacks your body, as if your body is a foreign invader within itself.  In a healthy immune system, the protective proteins recognize normal body proteins as 'self'.  The 'self' proteins are supposed to be ignored by the immunity cells.  The problem comes when this recognition system breaks down and 'self proteins' are interpreted as invading proteins.  This attack on 'self' leads to autoimmunity. 

Although millions of men suffer from autoimmune issues, it's primarily a disease of women.  Many theories are being investigated to help define why 75% of autoimmune sufferers are women, but there have been no conclusive results yet.  Fortunately, the research on treatment of AIs has led to some breakthroughs that improve the lives of sufferers.  The difficulties associated with diagnosing AIs, and the complexity of studying a disease with a genetic-environmental interaction, hampers the ability of researchers to focus in on causitive conditions.[4]

The tendency for autoimmune diseases to run in families suggests a strong genetic component, but inconsistent appearance and severity point to environmental factors as having a prominent role in developing any particular autoimmunity.  If a family member has an AI, you are more likely to develop an AI, but it's not a certainty.  The genetics are complex, and no one gene or gene group has been found that can be clearly linked to the chance of developing an autoimmune response.   Celiac disease may be the only autoimmune disease identified for which an environmental trigger has been identified, gluten, and the disease is currently treated by removing gluten from the diet forever.   Very recent studies have identified an additional environmental trigger that appears to be linked to the incidence of other autoimmune diseases.

 

DNACredit: Wikimedia commonsSalt millCredit: wikimedia commons

A series of fortunate events

Three recent studies published in the journal Nature suggest a surprising link between autoimmune disease and a simple environmental factor – salt.  By connecting a series of ideas, and testing them with experiments, researchers are creating a molecular model of how salt may affect the body’s inflammatory response.  An overblown inflammatory response is a factor of many autoimmune diseases, and by looking at a protein involved in the inflammatory pathway, researchers are beginning to suspect an effect of salt on autoimmune disease.

When the body’s immune system overreacts, the body begins to attack healthy tissue, a condition known as autoimmunity.  A hallmark of many, but not all, autoimmune diseases is inflammation.  Inflammation is a result of cytokine production and, when properly kept in check, is a normal healthy response to disease. Interleukin 17 (IL-17) is one of the proteins that can cause inflammation and is produced by TH17 cells.  These studies focus on those TH17 cells, a type of helper T cell. The overproduction of TH17 cells has been linked to some forms of autoimmunity.   Excess TTH17 cells leads to excess IL-17 which can contribute to autoimmune disease. 

The Regev Lab

Until now, the switch that led to overproduction of TH17 cells has been unknown, but Aviv Regev and her colleagues used nanowires to manipulate genes in immune cells, which allowed them to create a model of how TH17 cells are controlled.  By using the nanowires to turn genes on and off in the TH17 cells they were able to study individual genes and show which genes cause the TH17 cells to divide and proliferate.[1]

The Kuchroo Lab

An affiliated team led by Vijay Kuchroo discovered that TH17 cells are signaled by a protein called SGK1.  This protein helps to stabilize the TH17 cells through a series of additional proteins and signaling mechanisms. SGK1 was known to be necessary for sodium transport and maintaining salt concentrations in other cells. Kuchroo et al combined these two ideas and discovered that, when mouse cells are grown in high salt concentration, SGK1 is produced at higher levels and leads to an increase in TH17 cells.[2]

The Hafler Lab

A third group led by David Hafler confirmed Kuchroo’s findings in both mouse and human cells.  They also found that the TH17 cells generated under high salt conditions exhibit a pathogenic (disease causing) phenotype with an upregulation of several pro-inflammatory cytokines.  So not only does high salt lead to more TH17 cells, these TH17 cells are making a lot of cytokines that lead to inflammation.  They further investigated the effects of high salt by feeding mice a high salt diet. These mice developed a more severe form of an animal autoimmune disease.[3]

The short version:

Are you following so far?  Inflammation is a part of many autoimmune diseases.  TH17 cells make a protein that causes inflammation.  High salt leads to excess TH17 cells (and thereby more inflammation).  In mice, high salt leads to an autoimmune disease.

While it seems an easy jump to apply these findings in mice to humans, they are different species and the human response to salt may not be the same.  Clearly more studies are needed, including human studies with carefully controlled groups consuming monitored diets.  These recent publications do, however, show a lot of promise towards finding more environmental factors that contribute to autoimmune disease.

Does this mean you should follow a low-salt diet? Well, there are lots of good reasons for that already, but if you have been diagnosed with an inflammatory autoimmune disease such as psoriasis, it may be well worth the effort to cut down on salt and see if it helps your disease.

Autoimmune diseases are difficult to diagnose, and many sufferers are labeled "chronic complainers" for years before a definative diagnosis is made.  If you have chronic, unexplained fever, fatigue and malaise - three very common AI symptoms - convince your physician to begin testing for an autoimmune disease.  Making a definative list of every symptom you feel you have can help your physican narrow the possibilities and begin with testing for the most likely culprits.