Autoantibodies attacking the heart in lupus patients Credit Hand-drawn image by Xiaokan Zhang/Vunkak-Novakovic Lab

Cardiovascular disease is the primary cause of death in individuals with lupus, an autoimmune disease that occurs when the immune system attacks the body’s own tissues and organs, including the heart, blood, lungs, joints, brain, and skin. Lupus myocarditis, inflammation of the heart muscle, can be extremely serious as it can disrupt the normal rhythm and strength of the heartbeat. However, understanding the mechanisms of this complex disease is challenging and studying it is difficult.

A long-standing question about lupus is why some patients develop myocarditis while others remain unaffected, and why the clinical manifestations of affected patients range so dramatically, from no symptoms at all to severe heart failure. Lupus is characterized by a large number of autoantibodies, which are immune proteins that mistakenly target a person’s own tissues or organs, with different specificities for various molecules. These autoantibodies, similar to our genes, may explain why different individuals experience different symptoms.

Researchers have long suspected that certain autoantibody signatures may be the key to understanding the varied clinical presentations seen in lupus patients. Identifying the specific autoantibodies responsible for heart damage has been very difficult due to the lack of experimental models that accurately mimic the cardiac disease in lupus patients. The animal models currently used have limitations due to differences in cardiac physiology, and human cell cultures are unable to fully replicate the complexity and function of the human heart.

New study shows that autoantibodies can directly affect heart disease in lupus patient

The researchers created small cardiac tissues from healthy adult human stem cells, and then they matured the tissues using metabolic and electromechanical signals. Afterward, they exposed the tissues to the autoantibodies present in the blood of lupus patients who had myocarditis and those who did not. The team found that the way the patients’ autoantibodies attached to the heart tissue depended on the type and severity of their myocardial damage. Some patients with severe myocarditis had unique autoantibodies that mainly targeted dying cardiac cells, while those with weakened heart pump function had autoantibodies that mostly focused on the surface of live cells. Interestingly, the team also found that the autoantibodies binding to live cardiac cells could have powerful biological effects on the tissues without the presence of immune cells, potentially revealing new mechanisms that could lead to heart failure in lupus patients.

The study also identified four autoantibodies that may directly affect the heart muscle. These findings could assist in identifying lupus patients with the highest risk of developing heart disease, informing the development of new therapeutic strategies, and potentially extending to other autoimmune diseases.

“This study is the first to show that autoantibodies can directly cause injury to the heart in this complicated autoimmune disease,” said Gordana Vunjak-Novakovic, the leader of the team. She is the University Professor and the Mikati Foundation Professor of Biomedical Engineering, Medical Sciences, and Dental Medicine at Columbia. “It’s astonishing that the miniature heart tissues we’ve created using human stem cells and ‘organs-on-chip’ technology can replicate organ-level functions in a way that is specific to each patient, particularly for such a complex disease. We are now in an era where we can examine the progression and treatment of diseases using seemingly simple yet highly controllable and predictive models of human organs. It feels like we are living in the future.”