Genetics of Sjogren's Syndrome

Introduction

Sjogren's syndrome is an autoimmune condition. This syndrome's two most characteristic features are dry eyes and a dry mouth. This is because Sjogren's syndrome leads to inflammation and dysfunction of the lacrimal and salivary glands, producing much less moisture than it should. It can cause long-term dryness throughout the body. Sjogren's syndrome also has many other clinical manifestations, as it affects the body's immune system and other body parts, including the skin, joints, kidneys, digestive system, reproductive organs, lungs, and nervous system. Sjogren's syndrome can develop at any age but is most often diagnosed in people who are older than 40. Women are more commonly affected than men. The cause of Sjogren's syndrome is complex, involving genetic predisposition, immune dysregulation, and environmental factors. Medically, Sjogren's syndrome is classified into two types:

• Primary Sjogren's Syndrome - It develops independently and is not caused by other medical conditions.

• Secondary Sjogren's Syndrome - It occurs by the trigger of any other medical condition.

What Is the Relationship Between Sjogren Syndrome and Genetics?

Sjogren syndrome, like most autoimmune diseases, can run in families. The clinical studies and data about Sjogren syndrome are very limited. More data about this condition would benefit healthcare professionals, individuals, and their family members with Sjogren's syndrome. The genetic risk factor for developing this syndrome is 30 percent, like most autoimmune disorders. However, many other factors, like environmental, gender factors, and any triggering event, such as a virus, also play a key role in developing Sjogren's syndrome. Any changes can occur in the gene due to changes in the behaviors and environmental variations, called epigenetic factors. Gene variations occurring due to epigenetic factors may also be a reason for developing this condition. Genome-wide association studies (GWAS) have performed some studies on patients of European and Asian descent and Han Chinese. Some similarities have been noted, along with many differences. The specific genes that are responsible for Sjogren's syndrome vary by population. More studies are needed to know more about the familial risk of Sjogren syndrome.

1. HAL Gene - One of the most significant genetics responsible for Sjogren's syndrome is within the human leukocyte antigen (HLA) region, mainly the HLA-DR and HLA-DQ loci. Genetic studies have reported the differences in the genetic risk factors for Sjogren's syndrome across different ethnicities. For example, HLA-DR 3 and 2 loci are predominantly noted in white populations. HLA-DRB103 is a significant risk allele in Caucasian populations, whereas the same is less prevalent in Asian populations. A study also shows that primary syndrome caused by the HLA gene has increased anti-Ro/SSA (anti–Sjogren's-syndrome-related antigen A autoantibodies) and anti-La/SB (anti-Sjogren's syndrome B) autoantibody responses.

2. Non-HAL Gene - Non-HAL genes that are responsible for Sjogren's syndrome include cytokine receptors (for example., interferon regulatory factor 5), genes encoding cytokines (for example, interleukin-12A), genes involved in epithelial cell function and apoptosis (for example, FAS), and signaling molecules involved in immune cell activation (for example, STAT4).

Why Is Genetics of Sjogren Syndrome Important?

Knowledge about the genetic influence of Sjogren syndrome will be very beneficial in developing targeted therapies. Targeted therapy uses drugs that target specific genes and proteins that may be responsible for the disease, stop its growth, and destroy it. Knowing the key genes and pathways causing the syndrome will be advantageous for researchers in creating new therapeutic targets and producing precision medicine approaches for personalized treatment.

For example, drugs targeting specific immune pathways involved in Sjogren's syndrome, such as cytokine signaling or B-cell activation, are being investigated in clinical trials. Drugs that target B cells, like Rituximab or cytokines like Interferon-alpha, have been shown to reduce the symptoms in individuals with Sjogren syndrome. Also, identifying biomarkers will help predict disease progression, classify individuals based on risk profiles, and check treatment responses. Genetic testing will help identify individuals at greater risk of developing severe complications, such as lymphoma or systemic involvement. This will require medical professionals to provide early intervention and personalized treatment.

What Is the Treatment for Sjogren Syndrome?

There is no cure for Sjogren syndrome, so the healthcare provider will provide treatment for managing the symptoms. In most people, treatment may not be needed to manage symptoms like dry eyes and mouth. Home remedies like sipping more water and using over-the-counter eye drops may effectively control the symptoms. However, some people may require treatment, which may include:

• Decrease Eye Inflammation - In moderate to severe cases of eye dryness, the eye may get irritated and inflamed, so healthcare professionals may prescribe Lifitegrast or Cyclosporine, which will lubricate the eyes and reduce inflammation.

• Punctal Plugs (Surgery for Dry Eyes) - An eye specialist can surgically seal some or all of the tear duct, which drains the tears from the eyes, to keep the natural tears in the eyes for longer, thereby relieving dryness.

• Saliva Producers - Dentists may suggest over-the-counter supplements or prescriptions like Pilocarpine and Cevimeline to increase saliva production. Some prescription drugs have side effects like excess sweating, increased urination, abdominal pain, and flushing. So it is suggested to follow home remedies like sipping water throughout the day, chewing gum, or sucking on ice chips, which will help to maintain the moisture level in the oral cavity.

• Dental Care Products - Excess dryness can lead to many dental issues, like caries. So, people with Sjogren's syndrome should have frequent dental check-ups, special fluoride treatments, cleanings, or use prescribed toothpaste and mouthwash.

• Address Complications Associated With Sjogren Syndrome - Some individuals may develop other autoimmune disorders, like arthritis symptoms, and healthcare professionals may prescribe nonsteroidal anti-inflammatory drugs (NSAIDs) or arthritis drugs to alleviate pain.

• Vaginal Moisturizers - The healthcare provider may provide over-the-counter or prescription lubricants that help to maintain the moisture of the vagina. It can be used daily or during sexual intercourse.

Conclusion

Sjogren's syndrome is an autoimmune condition affecting the lubricating glands, such as the lacrimal and salivary glands, causing dryness in the mouth and eyes. It can also affect other body parts. As with most autoimmune disorders, Sjogren's syndrome also runs in families. Many studies are conducted to understand and identify genetic risk factors, which may help provide effective management for the condition and early identification of the disease's progression.