Our group has a focus on learning from the natural histories of rare primary immunodeficiencies (PID), i.e. those with onset early in life and treatable by hematopoietic stem cell transplantation (HSCT).
- Natural history studies on indication and outcome of primary immunodeficiencies (PID) requiring hematopoietic stem cell transplantation (HSCT) – e.g. combined immunodeficiencies and XIAP deficiency. What is the evolution of a particular PID condition with and without HSCT? Are there clear clinical/laboratory indicators which can identify patients, who are at a particular risk for critical complications? How can this knowledge improve our clinical care for these vulnerable patients? One main research focus since 2011 in this regard has been a long-term prospective outcome study on patients with profound combined immunodeficiency (P-CID). In this IEWP-EBMT anchored international multicenter study (conducted together with S. Ehl, Freiburg) the group follows >120 P-CID patients with and without HSCT and explores clinical, genetic and laboratory factors predictive of outcome.
- Newborn Screening for severe congenital T cell lymphopenia: What is the incidence of severe congenital T cell lymphopenia in Germany and how does the introduction of newborn screening since August 2019 improve early diagnosis, management and outcome? What are the underlying genetic conditions and how do they differ (e.g. influenced by migration factors) to other Western countries (e.g. North America). How can we connect existing patient registries to follow and understand these patients long-term? To address these questions Carsten Speckmann is guiding a collaborative registry effort of the German Society for Newborn Screening (DGNS), German Pediatric Working Party (API) and European Society for Immunodeficiencies (ESID). Carsten Speckmann is speaker of the German Pediatric Working Party (API) Screening Committee (AG Screening) and has accompanied the political process of SCID screening implementation in Germany over the past 10 years.
Combined immunodeficiencies (CID) are a heterogeneous group of inherited immune disorders with impaired T cell development or function manifesting through increased susceptibility to infections and/or immune dysregulation. Due to lack of data on the natural history, there are currently no clear treatment concepts for patients with P-CID, in particular with respect to the appropriate indication and time point for HSCT. This P-CID cohort will include patients with “atypical” SCID (mutation in a SCID causing gene, but manifestation after 1 year of age), patients with a range of rare defined primary immunodeficiencies, but also patients with so far genetically undefined combined immunodeficiencies. At study entry, the local center decides and carefully documents, whether and why the patient undergoes HSCT or not. Patients who are not transplanted are followed up yearly and severe events related to the PID as well as decisions for secondary HSCT are documented. Patients undergoing HSCT also have standardized follow-up evaluation schedules. All patients will be analyzed with respect to survival, frequency of severe events (infections, immune dysregulation, HSCT related complications) and quality of life. A concomitant genetic and immunological study will aim at a better phenotypic characterization and elucidation of new genetic causes for P-CID. This first prospective outcome study on P-CID will provide important information on prognosis and treatment decisions in this potentially life-threatening disease. The study is anchored with the EBMT-IEWP network.
SCID newborn screening
Newborn screening for SCID has been implemented in the routine nationwide screening program in August 2019. The impact of early diagnosis on treatment and outcome for SCID patients in Germany will be investigated by a collaborative registry effort of the German Society for Newborn Screening (DGNS), German Pediatric Working Party (API) and European Society for Immunodeficiencies (ESID).
- Clinical and molecular heterogeneity of RTEL1 deficiency. Speckmann, S. S. Sahoo, M. Rizzi, S. Hirabayashi, A. Karow, N. K. Serwas, M. Hoemberg, N. Damatova, D. Schindler, J.-B. Vannier, S. J. Boulton, U. Pannicke, G. Göhring, K. Thomay, J. J. Verdu-Amoros, H. Hauch, W. Woessmann, G. Escherich, E. Laack, L. Rindle, M. Seidl, A. Rensing-Ehl, E. Lausch, C. Jandrasits, B. Strahm, K. Schwarz, S. R. Ehl, C. Niemeyer, K. Boztug, and M. W. Wlodarski. Front Immunol 8: 449, 2017
- A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis. Speckmann, S. Doerken, A. Aiuti, M. H. Albert, W. Al-Herz, L. M. Allende, A. Scarselli, T. Avcin, R. Perez-Becker, C. Cancrini, A. Cant, S. Di Cesare, A. Finocchi, A. Fischer, H. B. Gaspar, S. Ghosh, A. Gennery, K. Gilmour, L. I. Gonzalez-Granado, M. Martinez-Gallo, S. Hambleton, F. Hauck, M. Hoenig, D. Moshous, B. Neven, T. Niehues, L. Notarangelo, C. Picard, N. Rieber, A. Schulz, K. Schwarz, M. G. Seidel, P. Soler-Palacin, P. Stepensky, B. Strahm, T. Vraetz, K. Warnatz, C. Winterhalter, A. Worth, S. Fuchs, A. Uhlmann, and S. Ehl. J Allergy Clin Immunol 139: 1302–1310, 2017.
- X-linked inhibitor of apoptosis (XIAP) deficiency: the spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis. Speckmann, K. Lehmberg, M. H. Albert, R. B. Damgaard, M. Fritsch, M. Gyrd-Hansen, A. Rensing-Ehl, T. Vraetz, B. Grimbacher, U. Salzer, I. Fuchs, H. Ufheil, B. H. Belohradsky, A. Hassan, C. M. Cale, M. Elawad, B. Strahm, S. Schibli, M. Lauten, M. Kohl, J. J. Meerpohl, B. Rodeck, R. Kolb, W. Eberl, J. Soerensen, H. von Bernuth, M. Lorenz, K. Schwarz, U. Zur Stadt, and S. Ehl. Clin Immunol 149: 133–141, 2013.
- Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency. Speckmann, U. Pannicke, E. Wiech, K. Schwarz, P. Fisch, W. Friedrich, T. Niehues, K. Gilmour, K. Buiting, M. Schlesier, H. Eibel, J. Rohr, A. Superti-Furga, U. Gross-Wieltsch, and S. Ehl. Blood 112: 4090–4097, 2008. (IF16.6)
- Clonality analysis after retroviral-mediated gene transfer to CD34+ cells from the cord blood of ADA-deficient SCID neonates. Schmidt*, D. A. Carbonaro*, C. Speckmann*, M. Wissler, J. Bohnsack, M. Elder, B. J. Aronow, J. A. Nolta, D. B. Kohn, and C. von Kalle. Nat Med 9: 463–468, 2003. (*equal contribution)
Complete list of publications: https://pubmed.ncbi.nlm.nih.gov/?term=Speckmann%2C+Carsten+%5BAuthor%5D&sort=date
BMBF: Genetic and immunological variability in patients with lymphoproliferation and autoimmunity (ALPS) (Subproject within the PID-NET rare disease network to explore the nature of primary immunodeficiencies associated with abnormal lymphoproliferation, funding period 2014-2018)