Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schmetterer, KG; Seidel, MG; Körmöczi, U; Rottal, A; Schwarz, K; Matthes-Martin, S; Steinberger, P; Pickl, WF.
Two newly diagnosed HLA class II-deficient patients identified by rapid vector-based complementation analysis reveal discoordinate invariant chain expression levels.
Int Arch Allergy Immunol. 2010; 152(4):390-400
Doi: 10.1159/000288292
Web of Science
PubMed
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- Seidel Markus
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- Abstract:
- Background: Primary immunodeficiencies represent the 'molecular Achilles' heels' of human immunity. Detailed analyses of primary immunodeficiencies extend our knowledge of pivotal immunological processes, lead to novel diagnostic algorithms and shorten the time to diagnosis. Methods: Clinical/immunological phenotypes of 2 unrelated patients from Austria with combined immunodeficiency were determined. Leukocyte subpopulations of these patients, their parents and healthy controls were analyzed by flow cytometry. Patient-derived Epstein-Barr virus (EBV)transformed B cell lines were established and complemented by candidate cDNAs. Suspected mutations were confirmed by DNA sequencing. Results: Phenotyping revealed a lack of constitutive human leukocyte antigen (HLA) class II expression on antigen-presenting cells of both patients, compatible with MHC class II deficiency. Rapid vector-based complementation analysis of the patients' B cells identified HLA class II transactivator (CIITA) deficiency in patient VIP1 and regulatory factor X (RFX) AP deficiency in patient VIP2. CIITA deficiency was caused by a homozygous p. Glu381X mutation. RFXAP deficiency resulted from a homozygous p. Ser123ThrfsX15 mutation, not described in the Middle European population so far. Of note, HLA class II-associated invariant chain (Ii) expression levels were significantly reduced in VIP1 and 3 additional EBV-transformed B cell lines of CIITA-deficient patients but normal in EBV-transformed B cells from VIP2. In addition, peripheral blood B cells from the parents of VIP1 showed significantly reduced HLA-DR and -DP expression levels compared to healthy controls. Conclusions: Analysis of patients' intracellular Ii and their parents' surface HLA class II expression levels might help to identify CIITA-deficient patients already during initial phenotyping. Copyright (C) 2010 S. Karger AG, Basel
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Agammaglobulinemia -
- Antigens, CD3 - immunology
- Antigens, Differentiation, B-Lymphocyte - biosynthesis Antigens, Differentiation, B-Lymphocyte - genetics
- CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - pathology
- Cell Line -
- Cell Proliferation -
- DNA Mutational Analysis -
- Female -
- Histocompatibility Antigens Class II - biosynthesis Histocompatibility Antigens Class II - genetics
- Humans -
- Immunologic Deficiency Syndromes - genetics Immunologic Deficiency Syndromes - metabolism Immunologic Deficiency Syndromes - pathology Immunologic Deficiency Syndromes - physiopathology
- Infant -
- Lymphopenia -
- Male -
- Middle Aged -
- Mutation - genetics
- Nuclear Proteins - genetics
- Superantigens - immunology
- Trans-Activators - genetics
- Transcription Factors - genetics
- Find related publications in this database (Keywords)
- Immunodeficiency
- HLA class II deficiency
- MHC II deficiency
- Superantigens
- Invariant chain