The Genetics of Sjogren's

Researchers find six new Sjogren's syndrome genes

With the completion of the first genome-wide association study for Sjögren's syndrome, an international coalition of researchers led by scientists at the Oklahoma Medical Research Foundation has identified six new disease-related genes.

Their work appears in the journal Nature Genetics.

Sjögren's syndrome is an autoimmune disease in which the immune system becomes confused and turns against the body's moisture-producing glands, damaging the ability to produce saliva or tears. Common symptoms include dry eyes and dry mouth, but the disease can also affect other organs and cause a variety of additional symptoms including severe fatigue, arthritis and memory problems.

The Sjögren's Syndrome Foundation estimates as many as 4 million Americans have the disease. Despite outnumbering patients with lupus, multiple sclerosis and other more commonly recognized autoimmune diseases, research into Sjögren's has been slow, said OMRF scientist Kathy Sivils, Ph.D.

"One problem has always been identifying true Sjögren's patients and collecting enough samples, partly because there's still disagreement on the criteria for the disease and clinical testing is not easy," she said. "So much work goes into classifying patients that it makes building collections of samples more difficult."

This research required Sjögren's researchers from around the world putting together about 2,000 patient samples, which were tested against more than 7,000 healthy controls.

The results were exactly what the researchers were hoping to see. In addition to the previously known HLA gene related to the disease, the group was able to identify six new Sjögren's genes and begin working to understand their functions.

"This is a first step," said OMRF scientist Christopher Lessard, Ph.D., lead author of the paper. "Now that we've identified these genes, we can dig down and start to understand how these genetic variants alter normal functions of the immune system."

So far, the international team of researchers led by Sivils, called the Sjögren's Genetics Network, or SGENE, has found these disease-related genes:

  • IRF5 and STAT4 which are "master regulators" that activate cells during an immune response
  • CXCR5 directs traffic for lymphocytes and may help explain why immune cells target moisture-producing glands.
  • TNIP1 is a binding partner with another autoimmune disease-related gene, TNFAIP3, which "cuts the brakes" on the immune system.
  • IL12A is one subunit of a protein that acts as a messenger between cells and modulates immune responses.
  • BLK is a B-cell gene which might account for increased numbers of antibodies.

Currently, the only treatment for Sjögren's syndrome is to target symptoms. Patients with chronic dry mouth use artificial saliva to chew and swallow. Dry eyes, which sometimes are difficult to open or blink, require artificial tears to function.

"I know it's a long ways off, but I hope these discoveries will open the door for researchers to find therapeutics that work at the genetic level to stop the disease," she said.

Thanks for sharing this. I was a little bit confused though. They said that the only treatment is to target symptoms. That's not right. . . People are put on DMARDs and biologics for Sjogren's as well, particularly when there is systemic involvement

Thanks, Stoney, for the correction. Anything you would like to post about treatment options would be helpful. I'm just learning about Sjogren's myself.

Very interesting, dancermom. We finally have an answer as to why they have not done more research on SS. I do believe that all hope begins in the research lab, so we are on the way to better treatments in the future, hopefully for ourselves, if not for our children, and grandchildren!

Yes Stoney, I had been taking Enbrel for about 2 years, and was taken off it the first of the year by my GP. I had the worst flu/bronchitis/UTI of my life, and could not get over it. The Enbrel was targeting Psoriatic Arthritis, however, the first problem I noticed was not a severe spike in pain, but the increased dryness in my eyes and mouth!

Ok so I was diagnosed when I was preggo with Sjrogrens. I have celiac disease. Post pregnancy I followed up with a Rheumatologist and was told after shmiers test and other blood test I don’t have it. I have horrible allergies, joint pain etc… Was bitten by a tick at age 8 I’m now 26 got a lot of immune probs… I’m thinking I got Lyme disease :frowning:

We have a community for that, too, Celiacdiva, and SK and I are there as well. Feel free to belong to both. You can find the link to the Lyme community by scrolling down and looking at the communities list on the right hand side of the page.

Hi Celiacdiva,

There is some very good information and are lots of helpful people there, glad to help you with your concerns.

What a shame you were bitten, if I had my way children would never have to suffer more than a skinned knee!

Yes, children should be made invulnerable. :)