Genetics and Sjögren’s

Does Sjögren’s run in families?

Sjögren’s, like most autoimmune diseases, can run in families. The clinical risk data is limited in Sjögren’s, but data is needed and would be helpful to patients and clinicians advising patients and their families. Like most autoimmune diseases genetic risk factors account for roughly 30% of the overall risk of developing Sjögren’s, along with environmental and gender factors, and a triggering event, for example a virus. Factors involved in gene regulation also play a role in developing the disease, referred to as Epigenetic factors. The specific genes that confer risk in Sjögren’s vary by population. Genome Wide Association studies have been performed on patients of European, Han Chinese, and Asian descent. There are some similarities, but many differences. Therefore, it is important to interpret the published data that we do have in the context of the population and geography of where the study was performed. The data may or may not be relevant to your family. Even less is known about the familial risk of Sjögren’s in the setting of another autoimmune disease.

Both the Innate immune response, immediate to ward off an infection, and the Adaptive immune response, which in long-lasting (memory) and highly specific, are reflected in the Sjögren’s specific genes identified to date. Immune response genes have the highest density on the X-chromosome. Since females carry 2 copies of the X-chromosome (XX) compared to the one copy in males (XY), females may be more susceptible to immune dysregulation. Also, Sjögren’s patients may have fragments of virus incorporated in their genome, retroviral long interspersed nuclear element 1, which can activate the Innate immune system leading to increased Interferon production (Type 1 INF) which can fuel inflammation and autoimmunity.

Further research on the genetics and immune responses in Sjögren’s will lead to understanding the immune dysregulation that occurs in the disease, and guide strategies to regain balance in the immune system.

If my family member has Sjögren’s, should I get tested?

Not under most circumstances. Testing should be driven by the presence of symptoms that suggest an autoimmune disease, like Sjögren’s. However, if a family member has symptoms such as, joint pain, severe fatigue, dry eye, dry mouth, vaginal dryness, nerve pain, etc. the possibility of Sjögren’s should be considered, and appropriate consultation and testing performed. The presence of Interstitial Lung Disease (ILD), mucosal associated lymphoid tissue (MALT) Lymphoma, or Primary Biliary Cholangitis (PBC) in the family member should raise suspicion for Sjögren’s if any of the wide range of possible Sjögren’s symptoms are present.

The one situation where a female family member of a Sjögren’s patient might seek testing is prior to pregnancy to screen for the presence of the SSA (Ro) and/ or SSB (La) autoantibody. These autoantibodies are associated with neonatal lupus and fetal heart block, and preventive strategies can minimize risk. However, there are no studies that assess the risk/benefit of performing these screening tests on family members of a Sjögren’s patient. Individual cases should be discussed with a treating physician, rheumatologist, and/or possibly a high-risk fetal medicine specialist.

This article was first printed in the Foundation's patient newsletter for members, Conquering Sjögren's. Click here to learn more about becoming a member.