ABSTRACT
PURPOSE: Complete interferon-γ receptor 1 (IFN-γR1) deficiency is a primary immunodeficiency causing predisposition to severe infection due to intracellular pathogens. Only 36 cases have been reported worldwide. The purpose of this article is to describe a large novel deletion found in 3 related cases, which resulted in the complete removal of the IFNGR1 gene. METHODS: Whole blood from three patients was stimulated with lipopolysaccharide (LPS) and IFN-γ to determine production of tumor necrosis factor (TNF), interleukin-12 p40 (IL-12p40) and IL-10. Expression of IFN-γR1 on the cell membrane of patients' monocytes was assessed using flow cytometry. IFNGR1 transcript was analyzed in RNA and the gene and adjacent regions were analyzed in DNA. Finally, IL22RA2 transcript levels were analyzed in whole blood cells and dendritic cells. RESULTS: There was no expression of the IFN-γR1 on the monocytes. Consistent with this finding, there was no IFN-γ response in the whole blood assay as measured by effect on LPS-induced IL-12p40, TNF and IL-10 production. A 119.227 nt homozygous deletion on chromosome 6q23.3 was identified, removing the IFNGR1 gene completely and ending 117 nt upstream of the transcription start of the IL22RA2 gene. Transcript levels of IL22RA2 were similar in patient and control. CONCLUSIONS: We identified the first large genomic deletion of IFNGR1 causing complete IFN-γR1 deficiency. Despite the deletion ending very close to the IL22RA2 gene, it does not appear to affect IL22RA2 transcription and, therefore, may not have any additional clinical consequence.
Subject(s)
Gene Deletion , Immunologic Deficiency Syndromes/genetics , Opportunistic Infections/genetics , RNA, Messenger/genetics , Receptors, Interferon/genetics , Receptors, Interleukin/genetics , Adult , Blood Cells/drug effects , Blood Cells/immunology , Blood Cells/pathology , Child, Preschool , Chromosomes, Human, Pair 6 , Dendritic Cells/immunology , Dendritic Cells/pathology , Female , Gene Expression Regulation , Homozygote , Humans , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/physiopathology , Infant , Interferon-gamma/pharmacology , Interleukin-10/genetics , Interleukin-10/immunology , Interleukin-12 Subunit p40/genetics , Interleukin-12 Subunit p40/immunology , Lipopolysaccharides/pharmacology , Opportunistic Infections/immunology , Opportunistic Infections/physiopathology , Pedigree , Primary Cell Culture , RNA, Messenger/immunology , Receptors, Interferon/deficiency , Receptors, Interferon/immunology , Receptors, Interleukin/immunology , Sequence Analysis, DNA , Transcription, Genetic , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology , Interferon gamma ReceptorSubject(s)
Epstein-Barr Virus Infections/virology , Hematopoietic Stem Cell Transplantation , Immunologic Deficiency Syndromes/surgery , Lymphohistiocytosis, Hemophagocytic/surgery , Child , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/immunology , Humans , Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/immunology , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/virology , Male , Treatment OutcomeABSTRACT
Lymphangiomatosis is a rare disorder. It is commonly localised in the skeletal system and called Gorham's disease, and in thoracic or abdominal organs. Involvement of the pericardium is rare and has been described in less than 20 patients worldwide. The case of a 14-year-old boy presenting with asymptomatic chylopericardium and interstitial lung disease is presented. After lung biopsy, performed to confirm the diagnosis of pulmonary lymphangiomatosis, he developed chylothorax and massive loss of chyle via chest drains. Thoracic duct ligation did not result in clinical improvement. Treatment with interferon α2b was given and because of clinical deterioration radiotherapy was added to the treatment. This resulted in a rapid decrease of chyle production in the patient.
Subject(s)
Biopsy/adverse effects , Lung Diseases/congenital , Lymphangiectasis/congenital , Pericardial Effusion/etiology , Adolescent , Diagnosis, Differential , Humans , Lung Diseases/diagnosis , Lymphangiectasis/diagnosis , MaleABSTRACT
An 8-year-old girl presented with cramp and tingling of the hands due to hypocalcaemia caused by pseudohypoparathyroidism.