The case for severe combined immunodeficiency (SCID) and T cell lymphopenia newborn screening: saving lives…one at a time

Abstract

Severe combined immunodeficiency (SCID) is a group of syndromes resulting from genetic defects causing severe deficiency in T cell and B cell function. These conditions are life-threatening and result in susceptibility to serious infections. SCID is often fatal in the first year of life if not detected and properly treated. SCID and related T cell lymphopenias can be detected in newborns by a simple screening test, the T cell receptor excision circle (TREC) assay, using the same dried blood spot samples already collected from newborns to screen for other genetic disorders. The TREC assay facilitates the earliest possible identification of cases of SCID before opportunistic infections, irreversible organ damage, or death, thus allowing for the possibility of curative treatment through hematopoietic stem cell transplant and gene therapy. Infants receiving hematopoietic stem cell transplant in the first few months of life, after being identified through screening, have a high probability of survival (95–100%), along with lower morbidity. The TREC assay has proven to have outstanding specificity and sensitivity to accurately identify almost all infants with SCID (the primary targets) as well as additional infants having other select immunologic abnormalities (secondary targets). The TREC assay is inexpensive and has been effectively integrated into many public health programs. Without timely treatment, SCID is a fatal disease that causes accrual of exorbitant healthcare costs even in just 1 year of life. The cost of care for just one infant with SCID, not diagnosed through newborn screening, could be more than the cost of screening for an entire state or regional population. Continued implementation of TREC screening will undoubtedly enhance early diagnosis, application of treatment, and healthcare cost savings. The Jeffrey Modell Foundation helped initiate newborn screening for SCID in the USA in 2008 and continues its efforts to advocate for SCID screening worldwide. Today, all 50 states and Puerto Rico are screening for SCID and T cell lymphopenia, with 27 million newborns screened to date, and hundreds diagnosed and treated. Additionally, there are at least 20 countries around the world currently conducting screening for SCID at various stages. Newborn screening for SCID and related T cell lymphopenia is cost-effective, and most importantly, it is lifesaving and allows children with SCID the opportunity to live a healthy life.

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Abbreviations

US:

United States

PI:

Primary immunodeficiency

SCID:

Severe combined immunodeficiency

HHS:

US Department of Health and Human Services

DOA:

US Department of Agriculture

DOT:

US Department of Transportation

EPA:

US Environmental Protection Agency

OMB:

US Office of Management and Budget

PCR:

Polymerase chain reaction

QALY:

Quality of adjusted life year

NICU:

Neonatal intensive care unit

ADA:

Adenosine deaminase

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Acknowledgments

The authors profoundly thank the Jeffrey Modell Center Directors for their unwavering and enduring support; and, heartfelt thanks to the patients and their families, who inspire us every day with their courage and fortitude.

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Correspondence to Fred Modell.

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The authors declare that they have no conflict of interest except for the following:

Jordan Orange, MD, PhD, Takeda Consultant, Enzyvant Consultant, received speaking honoraria from Takeda, ADMA Scientific Advisory Board, author and editor in immunology for Up To Date receiving royalties.

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Quinn, J., Orange, J.S., Modell, V. et al. The case for severe combined immunodeficiency (SCID) and T cell lymphopenia newborn screening: saving lives…one at a time. Immunol Res 68, 48–53 (2020). https://doi.org/10.1007/s12026-020-09117-9

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Keywords

  • Severe combined immunodeficiency (SCID)
  • T cell lymphopenia
  • Newborn screening
  • Primary immunodeficiency (PI)
  • Jeffrey Modell Foundation (JMF)
  • Awareness
  • Education
  • Diagnosis
  • Treatment
  • Immunology