People with a rare immune disease often wait years before receiving the correct diagnosis. During that time, symptoms worsen, organs can become damaged, and the impact on daily life increases. On 19 May, Helen Leavis, Professor of Clinical Immunology at Utrecht University and internist-clinical immunologist at UMC Utrecht, delivered her inaugural lecture Unravelling dysregulated immunity – universal insights and rare diseases. In her lecture, she showed how new technologies, innovative treatments, and intensive collaboration can contribute to better care for people with complex immune diseases.
Our immune system protects us against bacteria, viruses, and other external threats. But when the regulation of that system is disrupted, people can become seriously ill. Sometimes the immune system is not active enough, leading to infections. In other cases, the immune system becomes overactive and causes inflammation that damages the body itself. In some patients, both occur at the same time. “A well-functioning immune system depends on balance,” Helen Leavis explains. “When that balance is disrupted, very severe diseases can develop.”
To illustrate what this means in practice, Helen shared the stories of two young women with HLH, a rare and life-threatening dysregulation of the immune system. Patients with HLH develop an extreme inflammatory response that can damage multiple organs.
The first patient, a 26-year-old woman, became critically ill after an Epstein-Barr virus infection, also known as glandular fever. Her immune system spiraled completely out of control. She developed inflammation in multiple organs and her blood values rapidly deteriorated. Despite intensive treatment with strong immunosuppressive drugs and chemotherapy, she died after a devastating illness.
The second story involved another young woman with a very similar condition. She too became critically ill following an Epstein-Barr virus infection and was admitted to the intensive care unit. Being at an international conference, Helen discussed her case with experts from abroad. This resulted in the recommendation to add a new biological therapy to her treatment. Thanks to close collaboration between physicians, researchers, the hospital pharmacy, international partners, and the healthcare inspectorate, the medication became available within hours. The treatment proved successful, and the patient is now recovering following a stem cell transplantation.
“With HLH, both patients and physicians start at a disadvantage,” says Helen. “Patients are often much sicker than they appear on the outside. Early recognition and rapid treatment by experts are crucial.” Treating these patients requires close collaboration between different specialties, including haematology, infectious diseases, intensive care, pulmonology, and clinical immunology. “As a clinical immunologist, I often feel like the spider in the web.”
One of the biggest challenges in rare immune diseases is early recognition. On average, it takes around five years before patients with a rare disease receive the correct diagnosis. New technologies can help shorten that time.
At UMC Utrecht, Helen works on applications of artificial intelligence (AI) and advanced DNA diagnostics to recognize disease patterns earlier. Techniques such as whole genome sequencing allow researchers to identify genetic causes of immune disorders with increasing precision. AI models also offer new possibilities.
Together with colleagues, Helen developed a clinical decision support tool that can help identify patients with an increased risk of immune deficiencies at an earlier stage.
“You cannot recognize what you do not know,” she says. “That is why we must continue to increase knowledge about rare immune diseases.”
Treatment options are also rapidly evolving. According to Helen, clinical immunology is ideally positioned to bring innovative therapies to patients more quickly. She highlighted stem cell transplantation in adults, CAR-T cell therapy, and drug repurposing: the use of existing medicines for new applications.
Several studies on these innovative treatments are currently ongoing at UMC Utrecht. Helen is also conducting research into common variable immunodeficiency (CVID), a disorder in which patients are unable to produce sufficient antibodies. Some of these patients also develop severe chronic inflammation. Together with researchers in the Netherlands and abroad, she is working on new insights and treatments for this patient group.
In her inaugural lecture, Helen also addressed the societal challenges surrounding rare diseases, including the often non-transparent reimbursement rules for expensive medicines. For many of these conditions, large clinical trials or treatment guidelines do not exist. As a result, access to new therapies is often difficult for these patients, even when physicians have strong indications that a treatment may be effective. “Patients with a rare disease also deserve access to proper treatment,” she emphasizes. “We need a system in which expertise, collaboration and real-world data carry more weight.”
According to Helen, this requires a different way of assessing effectiveness and reimbursement for medicines used in rare diseases.
Collaboration is a common thread throughout Helen’s work. Within UMC Utrecht, she works closely with the Center for Translational Immunology, the Department of Medical Microbiology and the Julius Center for Health Sciences and Primary Care. Internationally, she collaborates with experts and research centers in countries including Germany and the United States.
With her chair, Helen strengthens UMC Utrecht’s strategic research program Infection & Immunity. The focus is on improving diagnostics, developing innovative treatments and advancing personalized care for patients with rare immunological diseases.
Helen concluded her oration with a clear message: “I will continue to speak out and contribute to improving the quality of life of people with rare diseases.”
