CD4+ CD31+ recent thymic emigrants in CHD7 haploinsufficiency (CHARGE syndrome): a case.

Abstract

Lymphocyte counts <2000 cells/μL are associated with early death in infants with CHARGE (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) syndrome and CHD7 haploinsufficiency. Absence of recent thymic emigrants is also accompanied by an Omenn-like syndrome and infant death in CHD7 haploinsufficiency. Studies positively identifying recent thymic emigrants, in relation to CHD7 haploinsufficiency, are non-existent. Thirty two months of flow-cytometric work-up of an athymic (evaluated by four chest X-rays) infant, with a novel CHD7 deletion, demonstrated sparse (<50 cells/mm(3)) but continuous egress of recent thymic emigrants (CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+)) and homeostatic lymphocyte expansion. Infectious or autoimmune episodes (e.g., Omenn-like syndrome) were not detected (despite lymphocyte counts <2000 cells/μL) and excellent vaccination (tetanus, Haemophilus influenzae type B and pneumococcal conjugate vaccines) and proliferation (anti-CD3 and anti-CD28 stimulated) responses were recorded. Her CD4(+) T cells displayed Gaussian distributed TCR (CDR3) spectratypes (22 functional Vβ families). Her CD4(+) T cell profile was also characterized by a slightly increased proportion CD4(+) CD25(+) FoxP3(+) T cells. Since CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+) RTE are reported to be TCR diverse and to contain regulatory T cells, we found it important to report that continuously reduced numbers of CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+) RTE, in the context of CHD7 haploinsufficiency and despite severe lymphopenia, is consistent with an uneventful clinical outcome.

• Authors: Kristian Assing, Christian Nielsen, Maria Kirchhoff, Hans O Madsen, Lars P Ryder, Niels Fisker
• Journal: Human immunology (Hum Immunol) Vol. 74 Issue 9 Pg. 1047-50 (Sep 2013) ISSN: 1879-1166 [Electronic] United States
• PMID: 23747993 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Chemical References

• CD4 Antigens
• CD8 Antigens
• DNA-Binding Proteins
• FOXP3 protein, human
• Forkhead Transcription Factors
• Platelet Endothelial Cell Adhesion Molecule-1
• DNA Helicases
• CHD7 protein, human

Topics

• Adult
• Antibody Formation
• CD4 Antigens (metabolism)
• CD8 Antigens (metabolism)
• CHARGE Syndrome (genetics, immunology)
• Cell Growth Processes
• Child, Preschool
• DNA Helicases (genetics)
• DNA-Binding Proteins (genetics)
• Female
• Forkhead Transcription Factors (metabolism)
• Haploinsufficiency
• Homeostasis
• Humans
• Infant
• Infant, Newborn
• Lymphocyte Count
• Lymphopoiesis (genetics)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Sequence Deletion (genetics)
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes, Regulatory (immunology)
• Thymocytes (immunology)
• Thymus Gland (immunology)
• Vaccination