Heart failure: autoimmune mechanism behind disease progression enables vaccine therapy

Research study conducted at Humanitas reveals that the progression of heart failure is driven by an autoimmune reaction targeting stressed heart tissues. Scientists have developed and tested a prototype vaccine designed to suppress inflammation and alleviate symptoms in a laboratory model of the disease.

Non-ischemic heart failure has traditionally been viewed as a mechanical-metabolic condition: the heart muscle, weakened by aging or increased workload due to vascular narrowing, struggles to pump blood effectively. However, a study conducted at the IRCCS Humanitas Research Hospital suggests that an autoimmune reaction may significantly contribute to disease progression. Immune cells called T lymphocytes recognize stressed heart tissue due to specific molecules produced under stress, infiltrate the organ, and activate inflammatory processes that impair its function.

This newly discovered mechanism could pave the way for innovative therapeutic strategies. Researchers identified some of the molecules that trigger the autoimmune response and used them to develop a prototype vaccine. Unlike traditional vaccines, which stimulate the immune system, this tolerizing vaccine retrains the immune system’s activation. Tested in an experimental model of the disease, the vaccine successfully prevented inflammation and improved heart function.

The study, published in Circulation Research, was led by Marinos Kallikourdis, Associate Professor at Humanitas University and Group Leader of the Adaptive Immunity Laboratory, and Gianluigi Condorelli, Full Professor at Humanitas University, Director of the Cardiology Research Program and Head of the Cardio Center at IRCCS Humanitas Research Hospital.

“For the first time, our work demonstrates that non-ischemic heart failure has a strong autoimmune component. Its progression is driven by the recognition of specific molecules – known as autoantigens – by T lymphocytes. Moreover, such molecules are sufficient to produce symptoms, which can be mitigated by targeting the immune activation mechanism,” explained Kallikourdis and Condorelli. “Although our findings are currently limited to an experimental model of the disease, the next steps involve validating these results in clinical settings and developing safe methods to bring these solutions to patients. It’s a long road, but one worth traveling.”

The Immune System’s Role in Heart Failure

Heart failure is a common and debilitating condition affecting approximately 600,000 people in Italy – one in ten individuals over 65. In industrialized countries, it remains a leading cause of disability and mortality among the elderly.

Despite the availability of therapies such as ACE inhibitors, sartans, aldosterone antagonists, and beta-blockers, developing more effective treatments remains a significant challenge in modern cardiology. Humanitas is at the forefront of innovative research in this field.

“Over the last decade, advancements in cardio-immunology have revealed the critical role of inflammation and immune cell recruitment in heart failure progression. Without these processes, the disease would not advance to the severe condition we know today,” noted Prof. Gianluigi Condorelli. “This study, published in Circulation Research, offers new insights: for the first time, we have demonstrated that heart failure have many features of an autoimmune disorder.”

The Study: Heart Failure as an Autoimmune Disease

Using novel methods developed at Humanitas to analyze proteins involved in immune processes, scientists studied a laboratory model of heart failure. They identified key molecules produced by the stressed heart that activate pro-inflammatory immune processes.

“In addition to demonstrating in the laboratory that these molecules are sufficient to activate the immune system and impair heart function, we analyzed blood samples from patients with heart failure and detected immune cells capable of recognizing those very molecules: further evidence of their clinical relevance” notes Marco Cremonesi, a researcher at Humanitas and one of the lead authors of the study, alongside Elisa Martini and Arianna Felicetta

Finally, the team developed and tested a prototype tolerizing vaccine that suppresses – rather than stimulates – the immune response, promoting tolerance to the identified molecules.

“These preliminary experiments demonstrate that recognizing heart failure as a disease with strong autoimmune features opens the door to innovative and more effective therapies,” said Marinos Kallikourdis. “The prototype tolerizing vaccine we tested exemplifies how cardio-immunology can revolutionize cardiology by leveraging immunology-based therapies to better treat cardiovascular diseases.”