New study classifies atherosclerosis as an autoimmune disease

Atherosclerosis should be classified as an autoimmune disease. That is the conclusion of a new international study featuring Klaus Ley, MD, founding co-director of the Immunology Center of Georgia, part of the Medical College of Georgia at Augusta University, Georgia Research Alliance Bradley Turner Eminent Scholar Chair in Immunology and professor of physiology.

In autoimmune diseases, the immune system turns against its own body through pathogenic B or T cells that attack self proteins, leading to severe organ damage. The new study, “Artery tertiary lymphoid organs encode a pathogenic high-affinity autoantibody−autoantigen pair in atherosclerosis,” was recently published in Nature Cardiovascular Research and shows key similarities between atherosclerosis and established autoimmune diseases like Multiple Sclerosis, Type 1 Diabetes and Rheumatoid Arthritis.

“This study uses an ingenious approach that Dr. [Andreas] Habenicht, the senior author, developed,” Ley said. “B cell receptor heavy and light chain sequences from tertiary lymphoid organs were used to construct recombinant monoclonal antibodies, which were screened for binding atherosclerotic plaque.”

According to the American Heart Association, atherosclerosis is a condition where cholesterol joins with other substances to form plaque along the walls on inside of the arteries, causing the blood vessels to narrow and become less flexible. This research identifies high-affinity, autoreactive antibodies, which – subsequent to adoptive transfer into mice – accelerates atherosclerosis. One of the autoantibodies is directed against histone 2B. Although H2B is not atherosclerosis-specific, it seems to become accessible to the antibodies in atherosclerotic plaque.

For decades, researchers have debated whether atherosclerosis can be classified as an autoimmune disease because clear defining evidence has been lacking. Now, a team led by Habenicht, MD, of LMU University Hospital in Germany, and Changjun Yin, PhD, of Sun Yat-sen University in China, has reported findings suggesting that atherosclerosis meets several key criteria of an autoimmune disorder.

The researchers found that vaccinating mice with histone 2B accelerated the progression of atherosclerosis. They then strengthened these findings by analyzing data from a clinical study of 495 participants recruited from the general population in Guangzhou, China.

“Our data are likely to have transformative power, because they characterize atherosclerosis as an autoimmune disease,” Habenicht said. “They have fundamental and far-reaching implications for future research as they allow to develop new types of diagnostics and immunotherapeutics, before the development of myocardial infarcts and strokes. However, this study is only providing a glimpse into a long and challenging journey.”

Ley has spent more than two decades investigating the role of the immune system in atherosclerosis and how it contributes to plaque buildup in the arteries. His work centers on the growing evidence that atherosclerosis is an autoimmune disease, raising the possibility of treating it by targeting the immune response itself.

The ultimate goal of Ley’s research is to develop immune-based therapies that can slow down or reverse the disease. His team is exploring several promising approaches, designing tolerogenic treatments that teach the immune system not to attack the body’s own tissues. Together, these efforts could lead to new treatments that complement existing cholesterol-lowering drugs and lifestyle interventions.