PMID- 20197681
OWN - NLM
STAT- MEDLINE
DCOM- 20100901
LR  - 20171116
IS  - 1423-0097 (Electronic)
IS  - 1018-2438 (Linking)
VI  - 152
IP  - 4
DP  - 2010
TI  - Two newly diagnosed HLA class II-deficient patients identified by rapid 
      vector-based complementation analysis reveal discoordinate invariant chain 
      expression levels.
PG  - 390-400
LID - 10.1159/000288292 [doi]
AB  - 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.
CI  - Copyright 2010 S. Karger AG, Basel.
FAU - Schmetterer, Klaus G
AU  - Schmetterer KG
AD  - Institute of Immunology, Center for Physiology, Pathophysiology and Immunology, 
      Medical University of Vienna, Vienna, Austria.
FAU - Seidel, Markus G
AU  - Seidel MG
FAU - Kormoczi, Ulrike
AU  - Kormoczi U
FAU - Rottal, Arno
AU  - Rottal A
FAU - Schwarz, Klaus
AU  - Schwarz K
FAU - Matthes-Martin, Susanne
AU  - Matthes-Martin S
FAU - Steinberger, Peter
AU  - Steinberger P
FAU - Pickl, Winfried F
AU  - Pickl WF
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100303
PL  - Switzerland
TA  - Int Arch Allergy Immunol
JT  - International archives of allergy and immunology
JID - 9211652
RN  - 0 (Antigens, Differentiation, B-Lymphocyte)
RN  - 0 (CD3 Complex)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (MHC class II transactivator protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RFXAP protein, human)
RN  - 0 (Superantigens)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (invariant chain)
SB  - IM
MH  - Adult
MH  - Agammaglobulinemia
MH  - Antigens, Differentiation, B-Lymphocyte/*biosynthesis/genetics
MH  - CD3 Complex/immunology
MH  - CD4-Positive T-Lymphocytes/*metabolism/pathology
MH  - Cell Line
MH  - Cell Proliferation
MH  - DNA Mutational Analysis
MH  - Female
MH  - Histocompatibility Antigens Class II/*biosynthesis/genetics
MH  - Humans
MH  - Immunologic Deficiency Syndromes/*genetics/metabolism/pathology/physiopathology
MH  - Infant
MH  - Lymphopenia
MH  - Male
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Nuclear Proteins/*genetics
MH  - Superantigens/immunology
MH  - Trans-Activators/*genetics
MH  - Transcription Factors/*genetics
EDAT- 2010/03/04 06:00
MHDA- 2010/09/02 06:00
CRDT- 2010/03/04 06:00
PHST- 2009/02/23 00:00 [received]
PHST- 2009/10/14 00:00 [accepted]
PHST- 2010/03/04 06:00 [entrez]
PHST- 2010/03/04 06:00 [pubmed]
PHST- 2010/09/02 06:00 [medline]
AID - 000288292 [pii]
AID - 10.1159/000288292 [doi]
PST - ppublish
SO  - Int Arch Allergy Immunol. 2010;152(4):390-400. doi: 10.1159/000288292. Epub 2010 
      Mar 3.