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Researchers at the Medical Center - University of Freiburg are creating the basis for improved diagnostics and targeted therapy with a new classification of childhood immune diseases.

If autoimmune diseases occur in childhood and are accompanied by swollen lymph glands or an enlarged spleen, this indicates a congenital disorder of the immune system. The exact diagnosis is difficult, but crucial for therapy. A study conducted by the Center for Chronic Immunodeficiency at the Medical Center - University of Freiburg has now provided new insights into autoimmune lymphoproliferative diseases in children. Crucial biomarkers have been identified that allow different immune diseases to be differentiated. The study, funded by the Wilhelm Sander Foundation and the German Research Foundation, was published in the journal Lancet Haematology on January 30, 2024.

"We now have a better concept for diagnosing these complex immune diseases and offering tailored treatments," says Prof. Dr. Stephan Ehl, Medical Director of the Center for Chronic Immunodeficiency at the Medical Center - University of Freiburg and member of the Cluster of Excellence CIBSS - Centre for Integrative Biological Signalling Studies at the University of Freiburg. "This is an important step towards personalized medicine for children with these rare immune disorders."

When the body attacks its own blood

Autoimmune lymphoproliferative disorder (ALPS) is a congenital chronic disease in which a signaling pathway that keeps the immune system in balance is disrupted. Patients show excessive growth of lymphocytes and form autoantibodies against their own blood cells. With targeted drug therapy, the disease can be controlled very well and has a good prognosis. In many patients with these symptoms, however, the signaling pathway is intact. They are referred to as "ALPS-like", but often do not respond to ALPS treatment and have a more severe course.

Course of the study

The study, which was conducted between 2008 and 2022, examined 431 children with suspected ALPS, under the hypothesis that other signaling pathways are disturbed in the patients. 71 children were diagnosed with ALPS using highly specific biomarkers. In 90 children, disorders of several other signaling pathways were identified, for which targeted therapies were often possible. "The results show that there may be other genetic diseases in addition to ALPS," says Pauline Hägele, first author of the study and doctoral student at the Center for Chronic Immunodeficiency at the Medical Center - University of Freiburg. "Through our study, we have introduced the new classification of autoimmune lymphoproliferative immunodeficiencies (ALPID) for these patients. ALPID is a warning signal that the disease may be more serious than ALPS. At the same time, advanced genetic testing in ALPID patients can enable targeted therapies and thus prevent severe progression."

Original title of the publication: "Diagnostic evaluation of pediatric autoimmune-lymphoproliferative immunodeficiencies (ALPID): A prospective cohort study"
DOI: 10.1016/S2352-3026(23)00362-9
Link to the study:https://www.sciencedirect.com/science/article/pii/S2352302623003629?via%3Dihub