Lupus and the Immune System: When Defense Turns Into Attack

The immune system works hard to keep foreign substances out of the body, producing antibodies that eliminate bacteria, viruses, and cancer cells. But with lupus, the immune system recognizes itself as the foreign object, and suddenly the antibodies that defend against harmful invaders turn against the body. While the cause of lupus is undetermined, most scientists believe that genes, hormones, and other environmental factors working together are what trigger the immune system’s betrayal against the body.

*Disclaimer:

The information provided in this article is for general informational purposes only and is not intended as medical advice. It should not be used as a substitute for professional diagnosis, treatment, or advice from a qualified healthcare provider. Reliance on any information provided in this article is solely at your own risk.

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According to John Hopkins Lupus Center, many patients with lupus have defects located in their major histocompatibility complex (MHC) genes. MHC genes typically code for antigen-fighting proteins and protect you from invaders, but when defects arise, they can start producing autoantibodies.

Autoantibodies: Antibodies that fight against the body’s own proteins. Once produced, they’ll interact with the complement system, a group of proteins that are essential to the immune system and the body’s inflammatory response.

Inflammatory response: A natural response to injury that promotes recovery. When autoantibodies engage with complement pathways, inflammation can become widespread and cause severe tissue damage.

Even if the body doesn’t produce autoantibodies, its inflammatory response can still fail if the complement system’s genes are already defective. MHC III genes in particular can cause harmful, excessive inflammatory effects within the body. These genes code for the components of the complement system, and if those components are coded incorrectly, then the body will begin producing excessive, harmful inflammatory effects even without autoantibodies. With only a few faulty genes within the immune system, the body can begin systematically destroying itself.

Hormones help modulate, regulate, and maintain the immune system so that it can keep defending the body. However, just like how antibodies and the body’s inflammatory response can turn against itself, these hormones can turn against the body too.

Though not confirmed to have a definitive relationship, one of the main contributing hormones in lupus is assumed to be estrogen, which might explain why lupus tends to be more common in women.

Estrogen is a hormone produced by the endocrine system that is vital in female reproductive health and regulating skeletal, cardiovascular, and central nervous systems.

The endocrine system works hand-in-hand with the immune system, so if the hormones produced by the endocrine system are dysregulated, the immune system will naturally go down with it.

• Estrogen can promote inflammation and interact with special estrogen receptors that lead to an overproduction of autoantibodies.

• Estrogen reduces the effectiveness of cells that help prevent autoimmunity called regulatory T-cells, leading to an unstable immune system.

• Lupus flares occur less during menopause when estrogen levels are at a low and increase during pregnancy when they are at a high.

Alongside estrogen, other hormones like cortisol and testosterone may also play a role in lupus, though their effects are less documented compared to estrogen.

• Cortisol is an anti-inflammatory hormone that is produced when you are stressed and helps contain the immune system.

• When you’re constantly stressed, your immune system can develop an immunity to stress. In an attempt to overcome this immunity, your body will start accumulating cortisol and compromise your immune system. This may explain why some patients seem to develop lupus after extreme emotional stress.

Exposure to something in your environment that weakens the immune system could similarly lead to lupus.

For example, excessive exposure to UV light can lead to a suppressed and weakened immune system. Read more about how sunlight affects people with lupus.

Scientists are still trying to determine a cause for why lupus develops. However, we can be sure that defected genes, hormones, and other external factors may contribute to the disease. The immune system may be the body’s defender, but the moment an autoantibody is produced or hormone levels fall out of balance, the body is at risk of attacking itself.

Causes of Lupus | Johns Hopkins Lupus Center

Estrogen: Hormone, Function, Levels & Imbalances | Cleveland Clinic

Men and Lupus | Lupus Canada

Complement Deficiency | National Library of Medicine

Current Directions in Stress and Human Immune Function | National Library of Medicine

The genetic basis of autoantibody production | Science Direct

The Role of Hormones in Lupus: Why It’s More Common in Women | Rupa Health

What Causes Lupus? | Lupus Foundation of America