Non-SCID combined immunodeficiencies: a diagnostic and therapeutic challenge

• Antragsteller: Professor Dr. Stephan Ehl; Dr. Klaus Schwarz
• Fachliche Zuordnung: Kinder- und Jugendmedizin
• Förderung: Förderung von 2016 bis 2020
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 287543091

Non-SCID combined immunodeficiencies (CID) are rare immunodeficiencies defined by impaired T cell immunity leading to severe infections, autoimmunity and malignancies. The genetic basis of CID is heterogeneous. Haematopoietic stem cell transplantation (HSCT) iscurative, but it is unclear when a T cell deficiency is severe enough to justify the risks of HSCT. We postulate that nature and extent of the T cell deficiency and their evolution over time are key factors determining the prognosis for CID patients that are to some extent independent of the genetic diagnosis. This justifies consideration of individual rare CIDs as a group. EuroCID members have initiated in 2011 a prospective study on the natural history ofpatients with profound CID (P-CID). Here, we propose to perform a detailed genetic and longitudinal immunologic characterization of CID patients identified through the P-CID study or by TREC-based newborn screening. EuroCID will also include patients with Nijmegen breakage syndrome as genetically well-defined CID. Correlation of genetic and immunological findings with clinical data will (1) provide new insights into the limiting factorsof human T cell immunity by identification of new genes and genotype-immunotypephenotype relationships, (2) help to identify biomarkers predictive of a poor outcome and (3) allow the development of treatment recommendations concerning indication and time-point of HSCT. This is the first time that a prospective study systematically collects information ongenotype-immunotype-phenotype to define optimal treatment for CID patients.

• DFG-Verfahren: Sachbeihilfen
• Internationaler Bezug: Frankreich, Israel, Italien, Polen
• Kooperationspartnerinnen / Kooperationspartner: Professor Dr. Alessandro Aiuti; Professorin Dr. Hanna Gregorek; Despina Moshous, Ph.D.; Professorin Dr. Capucine Picard; Professorin Dr. Polina Stepensky