| Hypomorphic Rag mutations can cause destructive midline granulomatous disease. | |
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MedLine Citation:
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PMID: 20489056 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Destructive midline granulomatous disease characterized by necrotizing granulomas of the head and neck is most commonly caused by Wegener granulomatosis, natural killer/T-cell lymphomas, cocaine abuse, or infections. An adolescent patient with myasthenia gravis treated with thymectomy subsequently developed extensive granulomatous destruction of midface structures, palate, nasal septum, airways, and epiglottis. His lymphocyte numbers, total immunoglobulin G level, and T-cell receptor (TCR) repertoire appeared normal. Sequencing of Recombination activating gene-1 (Rag1) showed compound heterozygous Rag1 mutations; a novel deletion with no recombinase activity and a missense mutation resulting in 50% Rag activity. His thymus was dysplastic and, although not depleted of T cells, showed a notable absence of autoimmune regulator (AIRE) and Foxp3(+) regulatory T cells. This distinct Rag-deficient phenotype characterized by immune dysregulation with granulomatous hyperinflammation and autoimmunity, with relatively normal T and B lymphocyte numbers and a diverse TCR repertoire expands the spectrum of presentation in Rag deficiency. This study was registered at www.clinicaltrials.gov as #NCT00128973. |
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Authors:
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Suk See De Ravin; Edward W Cowen; Kol A Zarember; Narda L Whiting-Theobald; Douglas B Kuhns; Netanya G Sandler; Daniel C Douek; Stefania Pittaluga; Pietro L Poliani; Yu Nee Lee; Luigi D Notarangelo; Lei Wang; Frederick W Alt; Elizabeth M Kang; Joshua D Milner; Julie E Niemela; Mary Fontana-Penn; Sara H Sinal; Harry L Malech |
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Publication Detail:
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Type: Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural Date: 2010-05-20 |
Journal Detail:
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Title: Blood Volume: 116 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-27 Completed Date: 2010-09-30 Revised Date: 2011-08-29 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 1263-71 Citation Subset: AIM; IM |
Affiliation:
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Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. sderavin@niaid.nih.gov |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00128973 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Animals Cells, Cultured Forkhead Transcription Factors Gene Rearrangement Genes, Immunoglobulin Granulomatous Disease, Chronic / etiology*, pathology*, surgery Homeodomain Proteins / genetics*, physiology* Humans Immunoglobulin G / immunology, metabolism Immunophenotyping Lymphocytes / immunology, metabolism Male Mice Mutation, Missense / genetics* Recombinases / metabolism Severe Combined Immunodeficiency / etiology*, pathology* T-Lymphocytes, Regulatory / immunology, metabolism, pathology Thymectomy Transcription Factors Transgenes / physiology |
| Grant Support | |
ID/Acronym/Agency:
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N01-CO-12400/CO/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/APECED protein; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Homeodomain Proteins; 0/Immunoglobulin G; 0/Recombinases; 0/Transcription Factors; 128559-51-3/RAG-1 protein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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