title: Successful haploidentical hematopoietic stem cell transplantation in a patient with SCID due to CD3ε deficiency: need for IgG-substitution 6 years later.
abstract: BACKGROUND
  The CD3 co-receptor complex is essential for signal transduction after specific binding of the T-cell receptor (TCR). CD3E encodes the CD3ε chain, one of the protein components (γ-, δ-, ε- and ζ-chain) of the CD3 co-receptor. As previously reported in one family CD3ε deficiency causes SCID.
  
  
  METHODS
  We report on a patient with SCID due to CD3ε deficiency treated by HLA-haploidentical stem cell transplantation (SCT) (donor: mother) 15 years ago which resulted in development of normal T- and B-cell immunity. Despite conditioning donor cell engraftment was confined to T cells, while all other blood cell lineages remained of patient origin (split chimerism). In spite of normal functions, T-cell numbers never reached normal levels and naïve CD45+RA+ T-cells remained low. At 6 years after SCT the patient developed signs of humoral immunodeficiency, requiring regular substitution of IgG.
  
  
  RESULTS
  In a retrospective genetic work up 11 years after SCT, a homozygous splice site mutation in CD3E was identified resulting in the loss of CD3ε protein. The loss of B-cell function as observed in the patient was reflected by a lack of switched memory B cells. To rule out a primary role of CD3ε in B-cell function we studied expression of CD3E in B-cells which was found not to be expressed.
  
  
  CONCLUSIONS
  The clinical presentation of a secondary loss of specific humoral immunity in this constellation of split chimerism after allogeneic haploidentical SCT is unusual and unexpected in a patient with a primary T-cell defect. A most likely explanation is the gradual loss of T-helper-cell function.
authors: Institute of Transfusion Medicine, University Ulm, Germany.
authors: M
authors: M
authors: Fuehrer
authors: Institute of Transfusion Medicine, University Ulm, Germany.
authors: U
authors: U
authors: Pannicke
authors: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany.
authors: C
authors: C
authors: Schuetz
authors: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany.
authors: E-M
authors: EM
authors: Jacobsen
authors: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany.
authors: A
authors: A
authors: Schulz
authors: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany.
authors: W
authors: W
authors: Friedrich
authors: Institute of Transfusion Medicine, University Ulm, Germany.
authors: K
authors: K
authors: Schwarz
authors: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany.
authors: M
authors: M
authors: Hönig
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006720:Homozygote; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007223:Infant; D007231:Infant, Newborn; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D017252:CD3 Complex; C115335:CD3E protein, human; D007074:Immunoglobulin G