When 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 by Stephan Ehl (A01) at the the Centre for Chronic Immunodeficiency, 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 was published in the journal Lancet Haematology on 30 January 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 Centre for Chronic Immunodeficiency, Medical Center – University of Freiburg and member of the CRC 1160 at the University of Freiburg. ‘This is an important step towards personalised 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 signalling 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 signalling pathway is intact. They are labelled 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 signalling pathways are disturbed in the patients. Highly specific biomarkers were used to diagnose ALPS in 71 children. In 90 children, disorders of several other signalling 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 researcher at the Centre for Chronic Immunodeficiency.
‘Through our study, we have introduced the new classification of autoimmune lymphoproliferative immunodeficiencies (ALPID) for these patients. ALPID is a warning sign that the disease may be more serious than ALPS. At the same time, extended genetic testing in ALPID patients can enable targeted therapies and thus prevent severe progression.’
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
