When autoimmune diseases during childhood appear with swollen lymph glands and an enlarged spleen, this could be a sign for a congenital disorder of the immune system. A certain diagnosis is difficult, but crucial for treatment. In a study, conducted by the Center for Chronic Immunodeficiency at the University Medical Center Freiburg, new insights about autoimmune lymphoproliferative diseases in children could be made. To this end, various biomarkers were identified, which allow a distinction between different diseases of the immune system. The study, funded by the Wilhelm Sander Foundation and the DFG (German Research Foundation), was published on January 30th, 2024, in the scientific journal LancetHaematology.
“We now have a better concept for diagnosing these complex diseases of the immune system and for offering custom-made treatments”, says Prof. Dr. Stephan Ehl, medical director of the Center for Chronic Immunodeficiency at the University Medical Center Freiburg and member of the Cluster of Excellence CIBSS – Centre for Integrative Biological Signalling Studies at the University of Freiburg. “It is an important step in the direction of personalized medicine for children with these rare immune system disorders.”
When the Body attacks its own Blood
The autoimmune lymphoproliferative syndrome (ALPS) is a congenital chronic disease, characterized by a disruption of a signalling pathway responsible for keeping the immune system balanced. Patients show abnormal lymphocyte growth and build auto antibodies against their own blood cells. With targeted drug therapy, it is possible to keep this disease in check with a good prognosis. Many patients with these symptoms have an intact signalling pathway, though. They are “ALPS-like”, but oftentimes don’t respond to ALPS treatment and have a severe disease progression.
Course of the Study
The study, conducted from 2008 to 2022, examined 431 children with suspected ALPS, under the hypothesis that other signalling pathways were disrupted. ALPS was diagnosed in 71 children, using highly specific biomarkers. 90 children were diagnosed with disruptions of multiple other pathways, where oftentimes, specific treatments were possible. “The results show, that besides ALPS, other genetic conditions could be present”, says Pauline Hägele, first author of the study and doctoral candidate at the Centre for Chronic Immunodeficiency at the University Medical Center Freiburg. “We, through our study, have introduced the new classification as autoimmune lymphoproliferative immunodeficiencies (ALPID). ALPID is a warning signal that the disease could be more serious than ALPS. At the same time, further genetic examinations in ALPID patients could enable targeted therapies and prevent severe disease progressions.”
Original publication
Pauline Hägele, Paulina Staus, Raphael Scheible, Annette Uhlmann, Maximilian Heeg, Christian Klemann, Maria Elena Maccari, Henrike Ritterbusch, Martin Armstrong,
Ioana Cutcutache, Katherine S Elliott, Horst von Bernuth, Timothy Ronan Leahy, Jörg Leyh, Dirk Holzinger, Kai Lehmberg, Peter Svec, Katja Masjosthusmann, Sophie Hambleton, Marcus Jakob, Monika Sparber-Sauer, Leo Kager, Alexander Puzik, Martin Wolkewitz, Myriam Ricarda Lorenz, Klaus Schwarz, Carsten Speckmann, Anne Rensing-Ehl, Stephan Ehl, ALPID study group (2024). Diagnostic evaluation of pediatric autoimmune-lymphoproliferative immunodeficiencies (ALPID): A prospective cohort study. In: Lancet Hematology. DOI: 10.1016/S2352-3026(23)00362-9
CIBSS-profile of Prof. Dr. Stephan Ehl