JUN 29, 2016

What's Triggering Your Autoimmune Disease?

WRITTEN BY: Kara Marker

For not completely understood reasons, certain genetic and environmental factors influence the body’s immune system to attack itself in the form of over 80 types of autoimmune diseases. It is as if the body is responding to a virus that isn’t there, scientists from the Hospital for Special Surgery hypothesize. How can we reassure the immune system that there’s no reason to attack healthy cells?

According to senior study author Mary K. Crow, MD, viral sequences in our genome exist from thousands of years ago. The genetic material is not enough to cause disease, but they are just enough like the original virus DNA that genetic mutations can cause lymphocytes of the immune system to detect them as foreign and dangerous, recognition powerful enough to launch an immune attack.

Crow and her team sought to understand how the body can confuse these ancient viral sequences as pathogens, potentially uncovering ways to alter the human genome so the viral genes do not cause autoimmune diseases like lupus and Sjogren’s syndrome.

Lupus is the name given to an autoimmune attack on the skin, joints, and/or bodily organs. Lupus is especially known for constant flare-ups of symptoms followed by periods of stable health. More than five million people around the world are believed to have some form of lupus, which ranges in severity.

Pronounced “SHOW-grins” syndrome, the other autoimmune disease of interest to the study’s scientists causes dryness, fatigue, chronic pain, neuropathies, and lymphomas. Remarkably, 90 percent of Sjogren’s patients are women, with a total of more than four million Americans affected by this systemic disease.

Crow hypothesized that virus-like elements called LINE-1 (L1) retroelements could be at the root of causation for autoimmune disease. The idea is that abnormal expression of these elements causes immune cells to recognize them as a threat, activating the innate immune response to act immediately as well as the overproduction of interferon-1 (INF-1) that the rest of the immune systems understands as a signal to launch a massive immune attack on the cells with these elements.

Given a real viral invasion, the production of interferon is vital to human health. When there’s no real virus to attack, though, only healthy cells are affected.

The researchers took biopsies from the kidneys of 24 patients with lupus nephritis and salivary gland tissue biopsies from 31 patients with Sjogren’s syndrome. In comparison to healthy tissue biopsies, the researchers were able to confirm the activity of L1 retroelements in the activation of the innate immune response as well as interferon overproduction.

“It is intriguing to think that virus-derived elements in our genome are either quiet and don’t cause any trouble, or they get stirred up and contribute to disease,” Crow said. Her findings implicate L1 retroelements as well as potentially other similar virus-like elements from the human genome. With further research, Crow and her team could be close to introducing gene therapy as a way to prevent L1 retroelements and other ancient viral genome pieces from falsely activating the immune system.

The study was recently published in the journal Arthritis & Rheumatology.

Sources: Hospital for Special Surgery, Sjogren’s Syndrome Foundation, Lupus Foundation of America