edoc

Dominantly inherited combined immunodeficiency as a consequence of heterozygous germline mutations in V(D)J recombination enzymes.

Jauch, Annaïse Julie. Dominantly inherited combined immunodeficiency as a consequence of heterozygous germline mutations in V(D)J recombination enzymes. 2021, Doctoral Thesis, University of Basel, Faculty of Science.

[img] PDF
Restricted to Repository staff only until 31 March 2023.

21Mb

Official URL: https://edoc.unibas.ch/82523/

Downloads: Statistics Overview

Abstract

Human immunodeficiencies associated with biallelic mutations in genes required for the generation of the B and T lymphocyte antigen receptors are prototypic inborn errors of immunity. We detected novel heterozygous missense mutations in critical genes implicated in the B and T cell receptor generation, termed RAG1/RAG2 and LIG4 and demonstrated that those can be associated with clinically severe immunodeficiency and immune- dysregulation. By analyzing murine models with titrable in vivo RAG activity we experimentally linked Rag gene dosage to lymphocyte development, anti-viral immunity and immune dysregulation.
Our study widens the spectrum of immunological and clinical phenotypes associated with RAG and LIG4 deficiency, which might have important implications for future molecular diagnosis and enabling effective targeted therapeutic interventions.
Advisors:Recher, Mike
Committee Members:Hess, Christoph and Oxenius, Annette
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immunodeficiency (Recher)
UniBasel Contributors:Recher, Mike and Hess, Christoph
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:14109
Thesis status:Complete
Number of Pages:112
Language:English
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss141090
edoc DOI:
Last Modified:25 Jun 2021 04:30
Deposited On:24 Jun 2021 09:42

Repository Staff Only: item control page