title: Neonatal screening for severe combined immunodeficiency in Brazil.
abstract: OBJECTIVE
  To apply, in Brazil, the T-cell receptor excision circles (TRECs) quantification technique using real-time polymerase chain reaction in newborn screening for severe combined immunodeficiency and assess the feasibility of implementing it on a large scale in Brazil.
  
  
  METHODS
  8715 newborn blood samples were collected on filter paper and, after DNA elution, TRECs were quantified by real-time polymerase chain reaction. The cutoff value to determine whether a sample was abnormal was determined by ROC curve analysis, using SSPS.
  
  
  RESULTS
  The concentration of TRECs in 8,682 samples ranged from 2 to 2,181TRECs/μL of blood, with mean and median of 324 and 259TRECs/μL, respectively. Forty-nine (0.56%) samples were below the cutoff (30TRECs/μL) and were reanalyzed. Four (0.05%) samples had abnormal results (between 16 and 29TRECs/μL). Samples from patients previously identified as having severe combined immunodeficiency or DiGeorge syndrome were used to validate the assay and all of them showed TRECs below the cutoff. Preterm infants had lower levels of TRECs than full-term neonates. The ROC curve showed a cutoff of 26TRECs/μL, with 100% sensitivity for detecting severe combined immunodeficiency. Using this value, retest and referral rates were 0.43% (37 samples) and 0.03% (3 samples), respectively.
  
  
  CONCLUSIONS
  The technique is reliable and can be applied on a large scale after the training of technical teams throughout Brazil.
authors.affiliation: Department of Immunology, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: Marilia Pyles Patto
authors.initials: MP
authors.lastname: Kanegae
authors.affiliation: Department of Immunology, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: Lucila Akune
authors.initials: LA
authors.lastname: Barreiros
authors.affiliation: Department of Pediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Juliana Themudo Lessa
authors.initials: JT
authors.lastname: Mazzucchelli
authors.affiliation: APAE-SP, São Paulo, SP, Brazil.
authors.forename: Sonia Marchezi
authors.initials: SM
authors.lastname: Hadachi
authors.affiliation: APAE-SP, São Paulo, SP, Brazil.
authors.forename: Laura Maria
authors.initials: LM
authors.lastname: de Figueiredo Ferreira Guilhoto
authors.affiliation: Hospital Geral de Pirajussara, São Paulo, SP, Brazil.
authors.forename: Ana Lúcia
authors.initials: AL
authors.lastname: Acquesta
authors.affiliation: Department of Pediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil; Hospital Pimentas Bonsucesso, Guarulhos, SP, Brazil.
authors.forename: Isabel Rugue
authors.initials: IR
authors.lastname: Genov
authors.affiliation: Amparo Maternal, São Paulo, SP, Brazil.
authors.forename: Silvia Maia
authors.initials: SM
authors.lastname: Holanda
authors.affiliation: Hospital Nossa Senhora da Conceição, Porto Alegre, RS, Brazil.
authors.forename: Regina Sumiko Watanabe
authors.initials: RS
authors.lastname: Di Gesu
authors.affiliation: Department of Pediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Goulart
authors.affiliation: Department of Pediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Amélia Miyashiro Nunes
authors.initials: AM
authors.lastname: Dos Santos
authors.affiliation: Clínica de Medicina Preventiva do Pará (CLIMEP), Belém, PA, Brazil.
authors.forename: Newton
authors.initials: N
authors.lastname: Bellesi
authors.affiliation: Department of Pediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Beatriz Tavares
authors.initials: BT
authors.lastname: Costa-Carvalho
authors.affiliation: Department of Immunology, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, SP, Brazil. Electronic address: condino@icb.usp.br.
authors.forename: Antonio
authors.initials: A
authors.lastname: Condino-Neto
mesh_terms: D000367:Age Factors; D001938:Brazil; D059788:Dried Blood Spot Testing; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000097:blood* / Q000235:genetics; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016511:Severe Combined Immunodeficiency / Q000097:blood* / Q000175:diagnosis*; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D011948:Receptors, Antigen, T-Cell
keywords: Combined immunodeficiency; Imunodeficiência combinada; Imunodeficiência primária; Linfócitos T; Neonatal screening; Primary immunodeficiency; SCID; T lymphocytes; TRECs; Triagem neonatal