Efficient screening strategies for severe combined immunodeficiencies in newborns

Area of Science:

• Immunology
• Genetics
• Public Health

Background:

• Severe Combined Immunodeficiency (SCID) is a life-threatening inborn error of immunity affecting cellular and humoral immunity.
• Affected infants typically die within the first year without curative treatment like stem cell or gene therapy.
• SCID's early asymptomatic nature and improved outcomes with early intervention make it a candidate for newborn screening (NBS).

Purpose of the Study:

• To review the implementation and optimization of SCID screening in newborn populations.
• To discuss the impact of T-cell receptor excision circle (TREC) detection in NBS programs.
• To highlight the importance of efficient, cost-effective screening strategies and international harmonization.

Main Methods:

• Population-based screening using T-cell receptor excision circle (TREC) detection.
• Algorithm adjustments and second-tier tests to optimize screening efficiency and reduce false positives.
• Review of international NBS programs for SCID.

Main Results:

• Many countries have successfully implemented SCID screening using TREC detection.
• Optimized screening strategies balance sensitivity and specificity, managing secondary findings effectively.
• Harmonization of screening terminology facilitates international knowledge sharing.

Conclusions:

• Newborn screening for SCID is an effective public health strategy.
• Advancements in testing, including next-generation sequencing, will expand NBS for other inborn errors of immunity.
• Continued development of screening modalities and treatments promises improved outcomes for infants with IEI.