title: 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.affiliation: Department of Clinical Immunology, Odense University Hospital, Odense, Denmark. assing@dadlnet.dk
authors.forename: Kristian
authors.initials: K
authors.lastname: Assing
authors.forename: Christian
authors.initials: C
authors.lastname: Nielsen
authors.forename: Maria
authors.initials: M
authors.lastname: Kirchhoff
authors.forename: Hans O
authors.initials: HO
authors.lastname: Madsen
authors.forename: Lars P
authors.initials: LP
authors.lastname: Ryder
authors.forename: Niels
authors.initials: N
authors.lastname: Fisker
mesh_terms: D000328:Adult; D000917:Antibody Formation; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D058747:CHARGE Syndrome / Q000235:genetics / Q000276:immunology*; D048708:Cell Growth Processes; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D057895:Haploinsufficiency; D006706:Homeostasis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018655:Lymphocyte Count; D038041:Lymphopoiesis / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D060168:Thymocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D014611:Vaccination
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D004265:DNA Helicases; C491434:CHD7 protein, human