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Newborn Screening for Severe Combined Immunodeficiency: Analytic and Clinical Performance of the T Cell Receptor Excision Circle Assay in France (DEPISTREC Study)

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Abstract

Severe combined immunodeficiency (SCID) is characterized by a major T cell deficiency. Infants with SCID are asymptomatic at birth but die from infections in the first year of life if not treated. Survival rates are better for early treatment. SCID therefore meets criteria for newborn screening (NBS). T cell receptor excision circle (TREC) quantification is a reliable marker of T cell deficiency and can be performed using Guthrie cards. The DEPISTREC project was designed to study the feasibility, clinical utility, and cost-effectiveness of generalized SCID screening in France. About 200,000 babies from all over the country were screened at birth with a commercial kit. We determined assay performance and proposed a cutoff for classification of results. Our findings suggest that, given clearly established validation rules and decision-making procedures, the TREC assay is a suitably specific and sensitive method for high-throughput SCID screening. Clinical Trials: NCT02244450

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Abbreviations

BTA:

Beta-actin

C1:

low-TREC control

C2:

no-TREC control

C3:

high-TREC control

DBS:

Dried blood spot

NBS:

Newborn screening

PID:

Primary immunodeficiency

SCID:

Severe combined immunodeficiency

TREC:

T cell receptor excision circle

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Funding

PRMEN1322265N (French Ministry of Health)

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Authors and Affiliations

  1. Laboratoire d’Immunologie, CHU Nantes, 44093, Nantes, France

    Marie A. P. Audrain, Alexandra J. C. Léger, Caroline A. F. Hémont, Marie G. M. Rimbert, Aurore Prat, Enora M. Q. Pinel & Maxime A. G. Fournier

  2. Centre de Recherche en Transplantation et Immunologie UMR1064, Inserm, Université de Nantes, Nantes, France

    Caroline A. F. Hémont & Marie G. M. Rimbert

  3. Laboratoire de dépistage néonatal, CHU Nantes, Nantes, France

    Sophie M. Mirallié

  4. Service de Biochimie et Biologie Moléculaire Grand Est, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Lyon, France

    David Cheillan & Eléonore Divry

  5. Plateforme de Méthodologie et Biostatistique, Direction de la Recherche, CHU Nantes, Nantes, France

    Aurélie M-P. Le Thuaut & Véronique A. Sébille-Rivain

  6. Direction de la Recherche, Cellule Innovation, CHU Nantes, Nantes, France

    Cécile G. L. Dert

  7. Service d’oncologie pédiatrique, CHU Nantes, Nantes, France

    Caroline J. C. Thomas

Authors
  1. Marie A. P. Audrain
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  2. Alexandra J. C. Léger
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  3. Caroline A. F. Hémont
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  4. Sophie M. Mirallié
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  5. David Cheillan
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  6. Marie G. M. Rimbert
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  7. Aurélie M-P. Le Thuaut
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  8. Véronique A. Sébille-Rivain
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  9. Aurore Prat
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  10. Enora M. Q. Pinel
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  11. Eléonore Divry
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  12. Cécile G. L. Dert
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  13. Maxime A. G. Fournier
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  14. Caroline J. C. Thomas
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Contributions

Marie Audrain, Sophie Mirallie, Caroline Thomas, Cécile Dert, and Véronique Sébille-Rivain designed the study. Marie Audrain, Enora Pinel, Aurore Prat, Caroline Hemont, Marie Rimbert, David Cheillan, and Eléonore Divry collected the data, which was analyzed and interpreted by Marie Audrain, Alexandra Léger, Maxime Fournier, Caroline Thomas, Aurélie Le Thuaut, and Véronique Sébille-Rivain. The article was drafted by Marie Audrain, and all authors gave final approval.

Corresponding author

Correspondence to Marie A. P. Audrain.

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The authors declare that they have no conflict of interest.

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Audrain, M.A.P., Léger, A.J.C., Hémont, C.A.F. et al. Newborn Screening for Severe Combined Immunodeficiency: Analytic and Clinical Performance of the T Cell Receptor Excision Circle Assay in France (DEPISTREC Study). J Clin Immunol 38, 778–786 (2018). https://doi.org/10.1007/s10875-018-0550-7

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  • DOI: https://doi.org/10.1007/s10875-018-0550-7

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