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Background <p>Newborn screening (NBS) by quantification of T-cell receptor excision circles (TREC) identifies a considerable number of infants with T-cell lymphopenia (TCL) other than severe combined immunodeficiency (SCID). While some of these children have well-defined inborn errors of immunity (IEI), many lack a clear genetic diagnosis, complicating their management and causing prognostic uncertainty.</p> Objective <p>To characterize the natural history of non-SCID TCL detected through NBS in Swiss infants between 2019 and 2023.</p> Methods <p>Clinical, genetic and laboratory data from all non-SCID TCL cases were extracted from the national NBS registry and analyzed.</p> Results <p>Out of 435 985 screened infants, 42 patients were identified with non-SCID, non-congenital athymia TCL, without an obvious secondary cause. A clear genetic diagnosis of IEI was established in 20 (48%) patients. Infants with confirmed IEI had significantly lower total T-cell, CD4 + T-cell and recent thymic emigrant (RTE) counts on initial lymphocyte phenotyping. In contrast, those with an unclear genetic diagnosis despite full investigations demonstrated faster normalization of total T-cell counts (hazard ratio 5.2, 95% CI 1.9 to 14.5, <i>p</i> = 0.001). All infants with initial CD4 + T-cell &lt; 0.3 × 10<sup>9</sup>/L showed minimal recovery of T-cell counts and remained on long-term prophylactic measures. All infants with an unclear genetic diagnosis despite investigations were able to discontinue prophylaxis at median age 6 months without experiencing opportunistic or severe infections.</p> Conclusion <p>Infants with non-SCID TCL identified by NBS represent a heterogenous group, ranging from severe, persistent TCL to mild, transient lymphopenia. Management should be tailored based on individual immunological and genetic profiles.</p>

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Natural History of Swiss Infants with Non-SCID T-cell Lymphopenia Detected by Newborn Screening: A Cohort Study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月25日

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  • Maarja Soomann,
  • Seraina Prader,
  • Philipp K. A. Agyeman,
  • Geraldine Blanchard-Rohner,
  • Michael Buettcher,
  • Christian R. Kahlert,
  • Nicole Ritz,
  • Aikaterini Theodoropoulou,
  • Jana Pachlopnik Schmid,
  • Johannes Trück

摘要

Background

Newborn screening (NBS) by quantification of T-cell receptor excision circles (TREC) identifies a considerable number of infants with T-cell lymphopenia (TCL) other than severe combined immunodeficiency (SCID). While some of these children have well-defined inborn errors of immunity (IEI), many lack a clear genetic diagnosis, complicating their management and causing prognostic uncertainty.

Objective

To characterize the natural history of non-SCID TCL detected through NBS in Swiss infants between 2019 and 2023.

Methods

Clinical, genetic and laboratory data from all non-SCID TCL cases were extracted from the national NBS registry and analyzed.

Results

Out of 435 985 screened infants, 42 patients were identified with non-SCID, non-congenital athymia TCL, without an obvious secondary cause. A clear genetic diagnosis of IEI was established in 20 (48%) patients. Infants with confirmed IEI had significantly lower total T-cell, CD4 + T-cell and recent thymic emigrant (RTE) counts on initial lymphocyte phenotyping. In contrast, those with an unclear genetic diagnosis despite full investigations demonstrated faster normalization of total T-cell counts (hazard ratio 5.2, 95% CI 1.9 to 14.5, p = 0.001). All infants with initial CD4 + T-cell < 0.3 × 109/L showed minimal recovery of T-cell counts and remained on long-term prophylactic measures. All infants with an unclear genetic diagnosis despite investigations were able to discontinue prophylaxis at median age 6 months without experiencing opportunistic or severe infections.

Conclusion

Infants with non-SCID TCL identified by NBS represent a heterogenous group, ranging from severe, persistent TCL to mild, transient lymphopenia. Management should be tailored based on individual immunological and genetic profiles.