Content area
Full Text
DOI: 10.1007/s10875-007-9097-8
Journal of Clinical Immunology, Vol. 27, No. 5, September 2007 ( C
2007)
Two Patients with Complete Defects in Interferon Gamma Receptor-Dependent Signaling
JEROEN G. NOORDZIJ,1 NICO G. HARTWIG,2 FRANK A. W. VERRECK,4 SANDRA DE BRUIN-VERSTEEG,1,2 TJITSKE DE BOER,4 JAAP T. VAN DISSEL,3 RONALD DE GROOT,2 TOM H. M. OTTENHOFF,4 and JACQUES J. M. VAN DONGEN1,5
Received February 26, 2007; accepted April 5, 2007 Published online: 21 May 2007
Unusual susceptibility to mycobacterial infections can be caused by deleterious mutations in genes that encode the interferon- receptor 1 chain. Such mutations hamper the activation of macrophages by a type 1 immune response and result in enhanced survival of intracellular pathogens. We here report two patients with unusual mycobacterial infections, both diagnosed with homozygous deleterious interferon- receptor 1 gene mutations. Patient 1 became ill after Bacillus Calmette Gurin vaccination at the age of 9 months and died at the age of 18 months. She carried a homozygous C71Y mutation in the extracellular part of the mature interferon- receptor 1 protein, resulting in the lack of detectable protein expression and absence of interferon- dependent signaling. Patient 2 became ill at the age of 3 years, is still alive at 19 years of age, and has suffered from ve successive infection episodes with atypical mycobacteria. A homozygous splice-site mutation in intron 3 was identied, resulting in the deletion of exon 3 at the mRNA level and consequently a truncated interferon- receptor 1 protein with absence of the transmembrane domain. Protein expression and interferon- dependent signaling were not detectable. KEY WORDS: Mycobacterial infection; Flow cytometric analysis; Deleterious IFNGR1 mutations ; Splice-site mutation; ELISA.
Financial support: Revolving Fund 2000 of the Erasmus MC Rotterdam, Rotterdam, The Netherlands.
1Department of Immunology, Erasmus MC/University Medical Center Rotterdam, Rotterdam, The Netherlands.
2Department of Pediatrics, Division of Immunology and Infectious Diseases, Erasmus MC/ University Medical Center Rotterdam, Rotterdam, The Netherlands.
3Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
4Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
5To whom correspondence should be addressed to Department of Immunology, Erasmus MC/ University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; e-mail: [email protected].
INTRODUCTION
The interferon- receptor (IFN- R) consists of two chains, the ligand-binding...