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Characterization of Infants with Idiopathic Transient and Persistent T Cell Lymphopenia Identified by Newborn Screening—a Single-Center Experience in New York State

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Abstract

Purpose

Newborn screening (NBS) quantifies T cell receptor excision circles (TREC) and identifies infants with T cell lymphopenia (TCL). This study elucidates the demographics, laboratory characteristics, genetics, and clinical outcomes following live viral vaccine administration of term infants with transient or persistent idiopathic TCL.

Methods

A single-center retrospective analysis was performed from September 2010 through June 2018. Laboratory variables were compared with Mann-Whitney tests. Correlations between initial TREC levels and T cell counts were determined by Spearman tests.

Results

Twenty-two transient and 21 persistent TCL infants were identified. Males comprised 68% of the transient and 52% of the persistent TCL cohorts. Whites comprised 23% of the transient and 29% of the persistent cohorts. Median initial TREC levels did not differ (66 vs. 60 TRECs/μL of blood, P = 0.58). The transient cohort had higher median initial CD3+ (2135 vs. 1169 cells/μL, P < 0.001), CD4+ (1460 vs. 866 cells/μL, P < 0.001), and CD8+ (538 vs. 277 cells/μL, P < 0.001) counts. The median age of resolution for the transient cohort was 38 days. Genetic testing revealed 2 genes of interest which warrant further study and several variants of uncertain significance in immunology-related genes in the persistent cohort. 19 transient and 14 persistent subjects received the initial rotavirus and/or MMRV immunization. No adverse reactions to live viral vaccines were reported in either cohort.

Conclusion

Transient and persistent TCL infants differ by demographic, laboratory, and clinical characteristics. Select transient and persistent TCL patients may safely receive live attenuated viral vaccines, but larger confirmatory studies are needed.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

The authors thank Professor Christopher League for assistance with preparing figures for the manuscript.

Authorship Contributions

AMJ, RS, DWR, and VRB designed the study. AMJ, OE, EH, SZ, FD, EB, AI, CC, BNM, RS, DWR, and VRB contributed to data collection and analysis. AMJ, EH, RS, DWR, and VRB contributed to manuscript preparation. All authors reviewed the manuscript.

Funding

This was supported by a grant from the Immune Deficiency Foundation to Dr. Jongco.

Author information

Authors and Affiliations

  1. Division of Allergy & Immunology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA

    Artemio M. Jongco III, Elise Hon, Omer Elshaigi, Foysal Daian, Emily Bae, Amanda Innamorato, Catherine Capo, David W. Rosenthal & Vincent R. Bonagura

  2. Department of Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA

    Artemio M. Jongco III, Shouling Zhang, David W. Rosenthal & Vincent R. Bonagura

  3. Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA

    Artemio M. Jongco III, David W. Rosenthal & Vincent R. Bonagura

  4. Center for Health Innovations and Outcomes Research, Feinstein Institutes for Medical Research, Manhasset, NY, USA

    Artemio M. Jongco III

  5. ENT and Allergy Associates, New York, NY, USA

    Robert Sporter

  6. Division of Allergy & Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Robert Sporter & Shouling Zhang

  7. Division of Rheumatology, Allergy & Immunology, Stony Brook University School of Medicine, East Setauket, NY, USA

    Brianne Navetta-Modrov

  8. Center for Molecular Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA

    Vincent R. Bonagura

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  1. Artemio M. Jongco III
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Corresponding author

Correspondence to Artemio M. Jongco III.

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The authors declare that they have no conflict of interest.

Ethical Approval

The Northwell Health Institutional Review Board approved this study, Protocol 19-0150-CCMC.

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Earlier versions of this data were presented as posters and platform presentations at the annual meetings of the American Academy of Allergy, Asthma & Immunology, and the Clinical Immunology Society.

Supplementary Information

Supplemental Figure 1

Initial laboratory parameters. Median CD19+ (A), CD16/56+ (B) counts. (PNG 4948 kb).

High resolution image (TIFF 1521 kb).

Supplemental Figure 2

Initial TREC and T cell counts do not correlate. Transient (A) and Persistent (B) cohort. For the transient cohort, Spearman coefficients (r) were as follows: CD3+ r = 0.06, P = 0.81, CD4+ r = −0.01, P = 0.99, CD8+ r = 0.05, P = 0.83. For the persistent cohort, Spearman coefficients were as follows: CD3+ r = 0.27, P = 0.24, CD4+ r = 0.32, P = 0.15, CD8+ r = 0.13, P = 0.57. TREC = T cell receptor excision circle (PNG 4948 kb).

High resolution image (TIFF 1521 kb).

Supplemental Figure 3

Longitudinal B and NK cell counts for transient and persistent cohorts plotted against the 10th and 90th percentiles for aged matched controls. Transient cohort values are plotted for CD19+ B (A) and CD16/56+ NK (B). Persistent cohort values are plotted for CD19+ B (C) and CD16/56+ NK (D). Subject T22 did not have his CD16/56+ NK cells measured and thus is not represented on Plot B. NK = natural killer (PNG 4948 kb).

High resolution image (TIFF 1521 kb).

Supplemental Table 1

(DOCX 152 kb).

Supplemental Table 2

(DOCX 40.8 kb).

Supplemental Table 3

Longitudinal CD3+, CD4+, CD8+, CD19+ and CD16/56+ counts for the persistent (Tab 1) and Transient (Tab 2) TCL cohorts. Blacked out boxes indicate the absence of data for that subject. WNL indicates that the records stated that the T cell counts had normalized for that subject. (XLSX 34 kb).

Supplemental Table 4

(DOCX 32.5 kb).

Supplemental Table 5

(DOCX 108 kb).

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Jongco, A.M., Sporter, R., Hon, E. et al. Characterization of Infants with Idiopathic Transient and Persistent T Cell Lymphopenia Identified by Newborn Screening—a Single-Center Experience in New York State. J Clin Immunol 41, 610–620 (2021). https://doi.org/10.1007/s10875-020-00957-6

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