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- Study Description
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Important Links and Information
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- Instructions for requestors
- Data Use Certification (DUC) Agreement
- Talking Glossary of Genetic Terms
We identified germline heterozygous mutations in CTLA4 in members of four families with severe immune dysregulation. Human CTLA4 haploinsufficiency caused dysregulation of FoxP3+ regulatory T (Treg) cells and lymphocytic infiltration of target organs, mimicking Ctla4 homozygous mice. Patients also exhibited a B cell phenotype, with progressive loss of B cells and accumulation of autoreactive CD21lo B cells. This study demonstrates a critical quantitative role for CTLA-4 in human immune homeostasis.
- Study Design:
- Case Set
- Study Type:
- Case Set
- Total number of consented subjects: 5
- Subject Sample Telemetry Report (SSTR)
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- Authorized Access
- Publicly Available Data
- Link to other NCBI resources related to this study
- Study Inclusion/Exclusion Criteria
Inclusion criteria: Combination of hypogammaglobulinemia and/or CD4 lymphopenia, and infiltration of at least one non-lymphoid organ [brain, lungs and gastrointestinal tract] with lymphocytic aggregates, autoimmune cytopenia.
Exclusion criteria: Any known previously identified genetic defects for immune dysregulation and lymphoproliferation
- Molecular Data
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Type Source Platform Number of Oligos/SNPs SNP Batch Id Comment Whole Exome Capture Agilent SureSelect 38Mb N/A N/A Whole Exome Capture Agilent SureSelect Human All Exon v3 - 50Mb N/A N/A Next-Generation Sequencing Illumina HiSeq 2500 N/A N/A Next-Generation Sequencing Thermo Fisher Scientific SOLiD Next-Generation Sequencing N/A N/A - Selected Publications
- Diseases/Traits Related to Study (MeSH terms)
- Authorized Data Access Requests
- Study Attribution
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Principal Investigator
- Gulbu Uzel, MD. National Institutes of Health, Bethesda, MD, USA.
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Co-Principal Investigators
- Michael J. Lenardo, MD. National Institutes of Health, Bethesda, MD, USA.
- Thomas A. Fleisher, MD. National Institutes of Health, Bethesda, MD, USA.
- Stuart G. Tangye, PhD. Garvan Institute of Medical Research, Sydney, Australia.
- Eric Meffre, PhD. Yale University School of Medicine, New Haven, CT, USA.
- Dat. Q. Tran, MD. University of Texas Medical School, Houston, TX, USA.
- Steven M. Holland, MD. National Institutes of Health, Bethesda, MD, USA.
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Funding Sources
- Intramural Research. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
- Intramural Research Program, NIH , CC. National Institutes of Health, Bethesda, MD, USA.
- 1066694 (to S.G.T.). National Health and Medical Research Council of Australia (Cancer Council NSW), Canberra, Australia.
- 1027400 (to S.G.T.). National Health and Medical Research Council of Australia (Cancer Council NSW), Canberra, Australia.
- 1016953 (to S.G.T.). National Health and Medical Research Council of Australia (Cancer Council NSW), Canberra, Australia.
- RG 12-08 (to S.G.T.). National Health and Medical Research Council of Australia (Cancer Council NSW), Canberra, Australia.
- AI071087 (to E.M.). National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
- AI095848 (to E.M.). National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
- AI061093 (to E.M.). National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
- 5R01HL113304-01 (to D.Q.T.). National Institutes of Health, Bethesda, MD, USA.
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Principal Investigator