Understanding Lupus: What Causes This Complex Autoimmune Disease?

Lupus is a chronic autoimmune disease that affects millions of people worldwide. Unlike a typical immune system that fights off foreign invaders, the immune system of someone with lupus mistakenly attacks their own healthy tissues and organs, leading to inflammation and damage throughout the body. When that happens, it can cause a host of symptoms, most commonly pain and overall fatigue.

The big question remains: What exactly causes lupus?

While scientists haven't pinpointed a single, definitive cause, the current understanding is that lupus results from a complex interplay between several key factors: genetics, hormones, and environmental triggers.

1. The Role of Genetics

Lupus is not directly inherited like a simple trait, but having a family history does increase a person's risk. This suggests that certain genes—or combinations of genes—can predispose someone to develop the condition.

• Genetic Predisposition: Researchers have identified approximately 200 genes that are more commonly found in individuals with lupus. These genes are believed to influence the immune system's function, increasing the likelihood of malfunction when exposed to a trigger.

• Not a Guarantee: It's important to remember that simply having these genes is not enough to cause lupus. It only raises the risk, suggesting that another factor must "flip the switch."

"SLE is a polygenetic disease. Around 200 genes have been discovered (as of March 2025) that increase the risk for SLE. However, most people with these genes never develop SLE. Other internal factors (like female hormones and low vitamin D levels) and external factors (like cigarette smoke, ultraviolet light, etc) interact with these genes, leading to excessive immune system activation." - Dr. Don Thomas, The Lupus Encyclopedia Blog

2. Hormonal Factors

Though not a "woman's disease," lupus is far more common in women than in men (about 9 out of 10 people with lupus are female), and it most often develops during the reproductive years (ages 15 to 44). This strong gender link has led researchers to investigate the role of hormones, particularly estrogen.

• Estrogen Connection: Estrogen is known as an "immunoenhancing" hormone, which means it can boost the activity of the immune system. The higher estrogen levels in women may contribute to their stronger immune response, which in turn might make them more susceptible to autoimmune diseases like lupus.

• Low Vitamin D Levels: Vitamin D is not just a "vitamin" ...it is an essential hormone that impacts many aspects of one's health, including immune regulation. There have been many studies showing the correlation between vitamin D deficiency and increased disease activity in SLE patients.

3. Environmental Triggers

For people with a genetic and hormonal predisposition, something in the environment often acts as the "trigger" that initiates the disease or causes a flare-up of symptoms. These potential triggers can be various factors encountered in daily life:

• Sunlight (UV Light): Exposure to ultraviolet (UV) light, primarily from the sun, is a well-known trigger. For susceptible people, it can cause lupus skin lesions or spark an internal response that leads to a full-body flare.

• Infections: Exposure to certain viral infections, most notably the Epstein-Barr Virus (EBV), is believed to potentially initiate lupus or cause a relapse in some individuals.

• Medications: A condition known as Drug-Induced Lupus can be triggered by a reaction to certain prescription drugs, such as some blood pressure medications, anti-seizure drugs, and antibiotics. The symptoms typically disappear once the medication is stopped.

• Chemical Exposure: Exposure to certain toxins, such as silica dust (often in occupational settings) and cigarette smoke, has also been implicated as a potential environmental factor.

• Stress: While not a direct cause, severe emotional or physical stress (like surgery, injury, or major life events) is a common factor reported to precede a lupus flare-up.

4. T Cells and Interferon

Researchers have been investigating, identifying, and tracking imbalances in certain types of T cells in lupus patients. T cells are white blood cells that are an integral part of the immune system. In many instances, what has been discovered is that lupus patients have too many "T helper" cells and too few "regulatory T" cells. This imbalance leads to the production of autoantibodies that attack healthy cells and tissues.

Another implication of this imbalance involves interferon. Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses. Lupus patients tend to have excess type I interferon. Type I interferon helps fight viral infections, but in lupus, these high amounts of type I interferon communicate with white blood cells and are overactive, and attack healthy body parts by mistake. That is why the development of the new lupus treatment Anifrolumab (Saphnelo) is promising to many SLE patients because it interferes with type I interferon activity.

The Bottom Line

Currently, the most accepted model for the cause of lupus is a three-way convergence:

Genetics+Hormones+Environmental Triggers→Lupus

Until the precise cause is discovered, research continues to focus on how these three elements interact. Understanding these risk factors is crucial for early diagnosis, treatment, and managing the disease to help those living with lupus lead healthier, more fulfilling lives.

Compiled by Kelli Roseta

Sources:

• Mayo Clinic: https://www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20365789

• Lupus Foundation of America: https://www.lupus.org/resources/what-causes-lupus

• Johns Hopkins Lupus Center: https://www.hopkinslupus.org/lupus-info/lupus/

• WebMD: https://www.webmd.com/lupus/understanding-lupus-prevention

• Cleveland Clinic: https://my.clevelandclinic.org/health/diseases/4875-lupus

• MedlinePlus: https://medlineplus.gov/lupus.html

• Lupus Encyclopedia: Early Signs of Lupus: What to Look For (Updated) - The Lupus Encyclopedia

• The Rheumatologist: Lupus Immunology Findings Provide Insights for Rheumatologists - The Rheumatologist

**All resources provided by this blog are for informational purposes only, not to replace the advice of a medical professional. Kelli encourages you to always contact your medical provider with any specific questions or concerns regarding your illness.   All intellectual property and content on this site and in this blog is owned by morethanlupus.com.  This includes materials protected by copyright, trademark, or patent laws. Copyright, More Than Lupus 2025.