The Genetics of Lupus - An Overview

What Is Systemic Lupus Erythematosus?

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. Autoimmune disease is a condition in which one’s own immune system attacks their own tissues and causes inflammation and tissue damage in the affected part or organs. Systemic lupus erythematosus is the most common type of lupus.

Lupus can affect any body part, such as the joints, skin, lungs, kidneys, brain, and blood vessels. Common signs and symptoms include fatigue, fevers, skin rashes, hair loss, anemia, tingling sensations or white or blue color changes in the finger during a cold, and joint pain or swelling. This condition is not associated with any certain gene, but individuals with lupus often have family members with similar autoimmune conditions.

What Are the Risk Factors for Developing Lupus?

The following have the highest risk of developing lupus:

• Genetics: People with a family history of lupus have an increased chance of developing lupus. A study shows that about two percent of kids whose parents have lupus are more likely to develop lupus.

• Gender: Anyone can develop lupus. However, women have an increased chance of getting lupus compared to men. Women are about 9 to 10 times more inclined to get lupus than men.

• Age: Lupus is more commonly diagnosed in the 20s and 30s. However, even children and elderly people can get lupus.

• Race: African-American women are two to three times more prone for lupus than Caucasian women. Even Hispanic, Asian, and Native American women are commonly affected. However, a severe form of lupus is noted in African-American and Hispanic women.

Is Lupus Hereditary?

Lupus has an increased probability of having genetic or hereditary causes. However, environmental exposure also has a notable role in developing lupus. Genetic researchers were able to identify approximately 100 genetic variations that are linked to lupus. Some of the most common genes associated with lupus are IRF5 (interferon regulatory factor 5), NCF2 (neutrophil cytosolic factor 2), PTPN22 (protein tyrosine phosphatase non-receptor type 22), STAT4 (signal transducer and activator of transcription 4), and TREX1 (three prime repair exonuclease 1). Ongoing genetic research continues to identify many new genes that play a pivotal role in the development of lupus.

A recent study has identified that the TLR7 (toll-like receptor) gene could be one of the major genetic drivers of lupus. The main role of this gene is to activate the immune system. It is located on the X chromosome. Also, it is involved in recognizing and binding to other molecules.

This gene regulates the recognition of single-stranded RNA-based pathogens and then triggers the immune response by stimulating the immune system to produce more B cells.

So, an overactive TLR7 gene can mistakenly consider the body’s tissues and organs as pathogens and cause increased B cell production, leading to lupus development. However, more studies are still required to understand the genetic influence on the development of lupus fully.

Researchers say that not a single gene but many different genes are involved in developing this condition, which is called polygenic disease. Also, epigenetics, which means how the lifestyle and environment can make changes in the genes work, has also been involved in lupus development.

Many scientists agree that genes alone cannot trigger lupus in most people. Environmental factors also play a significant role in the development of lupus. More recent research suggests that multiple factors can contribute to the development of lupus, including medication, emotional stress, physical injuries, exposure to ultraviolet rays from the sun or even lightbulbs, strenuous activities, pregnancy and childbirth, and much more.

What Is the Prevalence of Lupus in Families?

Studies have shown that lupus does tend to run in families. There needs to be more information about the disease's hereditary factor for individuals willing to know if they or their family members are more prone to developing it. The evidence is mostly unreliable, but researchers have discovered some inherited tendencies.

There is no useful method for accurately predicting this condition in specific individuals. The siblings of those individuals with SLE have an increased risk compared to the general population. According to the Lupus Foundation of America, siblings of an individual with lupus have about a 20 percent chance of developing lupus later. Approximately five percent of children born to a parent with lupus have the chance of developing this disease.

In families with lupus people, all members have a higher load of lupus-causing genetic factors called alleles than normal people. People with lupus have more alleles than necessary; similarly, it is more likely to pass on to their closest relatives.

A better understanding of the disease-causing genetic loci and their involvement in specific lupus phenotypes is required to predict disease outcomes accurately. The studies regarding the same are ongoing. Also, the genetic factors that increase the SLE developing risk can increase the risks of other autoimmune diseases. This is why individuals with SLE have high risk for other autoimmune diseases, including autoimmune thyroid disease, rheumatoid arthritis, and others.

What Is the Treatment for Lupus?

There is no cure for lupus, but lupus management will help calm the symptoms. Lupus management mainly aims to prevent flares, treat the presenting symptoms, and reduce organ damage and other problems. Then, lupus management will depend on the patients presenting with illnesses.

The medications commonly used for lupus management include:

• Nonsteroidal Anti-inflammatory Drugs (NSAIDs) - These drugs help to reduce pain and swelling in the body.

• Corticosteroids - It acts by reducing swelling, tenderness, and pain. If taken in high doses, they help to calm the immune system.

• Antimalarial drugs - These drugs not only prevent malaria but also treat skin rashes, joint pain, fatigue, and lung inflammation.

• BLyS-specific Inhibitors - These drugs link the abnormal B cell production found in people with lupus.

• Immunosuppressive Agents - In severe cases of lupus, these medications are recommended. They can cause serious side effects.

Conclusion:

Lupus is a chronic autoimmune disease that runs in families. Genetic research is being conducted to determine the disease's exact link and heredity. There is no cure for this condition. However, the treatment is considerably better than in the past, and in the future, it will be far better still.