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"leaky" SCID - genetic and phenotypic variability of patients with (severe) combined immunodeficiency
Summary
| While complete loss-of function mutations in genes involved in lymphocyte development lead to classical SCID, the phenotype of patients with hypomorphic (leaky) mutations and/or somatic reversions in these genes is less predictable. In addition, infections can significantly modulate the immunological and clinical phenotype. This includes disturbances in the T cell repertoire, gd T cell expansions, dysregulation of IgE production and autoimmune manifestations such as cytopenias, eczema and inflammatory bowel disease. |
TCR-Spectratyping by P. Fisch |
We screen defined patient cohorts meeting the following criteria:
(i) patients with lymphopenia and signs of autoimmunity, lymphoproliferation or chronic eczematous or granulomatous skin or bowel disease with or without susceptibility to infection,
(ii) patients with marker infections indicative of T cell deficiency, but normal immunological screening tests.
These patients are analyzed with a panel of routine immunological screening tests. In some cases, characteristic patterns allow direct targeted analysis for known (S)CID diseases using protein-based assays followed by genetic sequencing. All patients are then studied individually, with respect to aspects of lymphocyte development, immune regulation and immune response to infection.
We also use mouse models of “leaky” SCID that show features of immune dysregulation similar to human patients. In particular, we study the impact of viral infections on the clinical and immunological phenotype of these mice. Lymphocytic choriomeningitis virus (LCMV) infection is used as a model for systemic infection and pneumonia virus of mice (PVM) is used as a model for a local respiratory infection. Following infection, the pattern, the kinetics and the extent of clinical manifestations of immune dysregulation is investigated. Moreover, we characterize the impact of infections on typical immunological features of “leaky” SCID.
Cooperation Partners
- Klaus Schwarz, Institut für Transfusionsmedizin, Universität Ulm
- Paul Fisch, Molekulare Pathologie, Pathologisches Instituts, Uniklinik Freiburg
- API - Arbeitsgemeinschaft Pädiatrische Immunologie
Funding
CCI Tandem Project 4 (BMBF)
"Genetic, immunologic and phenotypic variability of (severe) combined immunodeficiency"
SFB 620, TPA4, Deutsche Forschungsgesellschaft
"Immunologische Charakterisierung von Patienten mit angeborenen Immundefekten"
Publications
For an up-to-date list of publications by Prof. Stephan Ehl please see the PubMed search:
