Journal of Clinical Immunology

, Volume 32, Issue 1, pp 82–88

Newborn Screening for Severe Combined Immunodeficiency; The Wisconsin Experience (2008–2011)

  • James W. Verbsky
  • Mei W. Baker
  • William J. Grossman
  • Mary Hintermeyer
  • Trivikram Dasu
  • Benedetta Bonacci
  • Sreelatha Reddy
  • David Margolis
  • James Casper
  • Miranda Gries
  • Ken DeSantes
  • Gary L. Hoffman
  • Charles D. Brokopp
  • Christine M. Seroogy
  • John M. Routes
Article

Abstract

Severe combined immunodeficiency is a life-threatening primary immune deficiency characterized by low numbers of naïve T cells. Early diagnosis and treatment of this disease decreases mortality. In 2008, Wisconsin began newborn screening of infants for severe combined immunodeficiency and other forms of T-cell lymphopenia by the T-cell receptor excision circle assay. In total, 207,696 infants were screened. Seventy-two infants had an abnormal assay. T-cell numbers were normal in 38 infants, abnormal in 33 infants, and not performed in one infant, giving a positive predictive value for T-cell lymphopenia of any cause of 45.83% and a specificity of 99.98%. Five infants with severe combined immunodeficiency/severe T-cell lymphopenia requiring hematopoietic stem cell transplantation or other therapy were detected. In summary, the T-cell receptor excision circle assay is a sensitive and specific test to identify infants with severe combined immunodeficiency and severe T-cell lymphopenia that leads to life-saving therapies such as hematopoietic stem cell transplantation prior to the acquisition of severe infections.

Keywords

SCID TREC lymphopenia newborn screening 

Abbreviations

SCID

Severe combined immunodeficiency

HSCT

Hematopoietic stem cell transplantation

NBS

Newborn screening

TREC

T-cell receptor excision circles

References

  1. 1.
    Puck JM. Population-based newborn screening for severe combined immunodeficiency: steps toward implementation. J Allergy Clin Immunol. 2007;120(4):760–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Brown L, Xu-Bayford J, Allwood Z, Slatter M, Cant A, Davies EG, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117(11):3243–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Buckley RH. Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes. Immunol Res. 2011;49(1–3):25–43.PubMedCrossRefGoogle Scholar
  4. 4.
    Routes JM, Grossman WJ, Verbsky J, Laessig RH, Hoffman GL, Brokopp CD, et al. Statewide newborn screening for severe T-cell lymphopenia. JAMA. 2009;302(22):2465–70.PubMedCrossRefGoogle Scholar
  5. 5.
    Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2005;115(2):391–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Baker MW, Laessig RH, Katcher ML, Routes JM, Grossman WJ, Verbsky J, et al. Implementing routine testing for severe combined immunodeficiency within Wisconsin's newborn screening program. Public Health Rep. 2010;125 Suppl 2:88–95.PubMedGoogle Scholar
  7. 7.
    Baker MW, Grossman WJ, Laessig RH, Hoffman GL, Brokopp CD, Kurtycz DF, et al. Development of a routine newborn screening protocol for severe combined immunodeficiency. J Allergy Clin Immunol. 2009;124(3):522–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Douek DC, Vescio RA, Betts MR, Brenchley JM, Hill BJ, Zhang L, et al. Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution. Lancet. 2000;355(9218):1875–81.PubMedCrossRefGoogle Scholar
  9. 9.
    Accetta D, Syverson G, Bonacci B, Reddy S, Bengtson C, Surfus J, et al. Human phagocyte defect caused by a Rac2 mutation detected by means of neonatal screening for T-cell lymphopenia. J Allergy Clin Immunol. 2011;127(2):535–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Sirvent N, Monpoux F, Pedeutour F, Fraye M, Philip P, Ticchioni M, et al. Jacobsen's syndrome, thrombocytopenia and humoral immunodeficiency. Arch Pediatr. 1998;5(12):1338–40.PubMedCrossRefGoogle Scholar
  11. 11.
    Eberle P, Berger C, Junge S, Dougoud S, Buchel EV, Riegel M, et al. Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11.2 microdeletion and partial DiGeorge syndrome. Clin Exp Immunol. 2009;155(2):189–98.PubMedCrossRefGoogle Scholar
  12. 12.
    Griffith LM, Cowan MJ, Notarangelo LD, Puck JM, Buckley RH, Candotti F, et al. Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management. J Allergy Clin Immunol. 2009;124(6):1152–60.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • James W. Verbsky
    • 1
    • 2
  • Mei W. Baker
    • 3
    • 5
  • William J. Grossman
    • 1
    • 6
  • Mary Hintermeyer
    • 7
  • Trivikram Dasu
    • 1
  • Benedetta Bonacci
    • 1
  • Sreelatha Reddy
    • 1
  • David Margolis
    • 1
  • James Casper
    • 1
  • Miranda Gries
    • 7
  • Ken DeSantes
    • 5
  • Gary L. Hoffman
    • 3
    • 4
  • Charles D. Brokopp
    • 3
    • 4
  • Christine M. Seroogy
    • 5
  • John M. Routes
    • 1
    • 2
  1. 1.Department of PediatricsMedical College of WisconsinMilwaukeeUSA
  2. 2.Children’s Research InstituteMilwaukeeUSA
  3. 3.Wisconsin State Laboratory of HygieneUniversity of Wisconsin-MadisonMadisonUSA
  4. 4.Department of Population Health SciencesUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  5. 5.Department of PediatricsUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  6. 6.BiotheraEaganUSA
  7. 7.Department of Advanced Practice NursingChildren’s Hospital of WisconsinMilwaukeeUSA

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