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Relationship Between Severity of T Cell Lymphopenia and Immune Dysregulation in Patients with DiGeorge Syndrome (22q11.2 Deletions and/or Related TBX1 Mutations): a USIDNET Study

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Abstract

Purpose

DiGeorge syndrome has substantial heterogeneity with variable immune deficiency and dysregulation. Implicated immunopathology includes reduced thymic output and increased peripheral homeostatic proliferation with Th2 skewing and expansion of self-reactive cells. We hypothesized that T cell lymphopenia severity will be associated with higher odds of autoimmunity and/or asthma.

Methods

Using the US Immunodeficiency Network registry, we identified patients with 22q11.2 deletion (and/or TBX1). Initial absolute CD3+ T cell values were stratified: normal, 50–99% and below 50% of the lower limit of age-adjusted normal values. Patients with and without reported autoimmunity and asthma were compared using chi-square tests and multivariate logistic regression.

Results

Among 415 patients, autoimmunity was reported in 17 (4.1%), and asthma was reported in 28 (6.7%). Compared with those with no reported autoimmunity, patients with reported autoimmunity more frequently had low CD19+ B cells [3.3% (12/364) vs 28.6% (4/14); p = 0.002] and low IgG [6.2% (20/321) vs 29.4% (5/17); p = 0.005] levels. There were no statistically significant differences in other immune characteristics among those with and without reported asthma. Patients with absolute CD3 levels below 50% of age-adjusted normal values had higher odds of reported autoimmunity (n = 319, OR = 7.56, 95% CI = 1.58–36.17, p = 0.01) and reported asthma (n = 319, OR = 4.5, 95% CI = 1.06–18.93, p = 0.04) as compared with those with normal CD3 values, adjusted for age and low IgG.

Conclusions

Absolute CD3+ T cell counts below 50% of age-adjusted normal values may be associated with higher odds of autoimmunity and/or asthma in patients with DiGeorge syndrome and be potentially useful to identify higher-risk patients.

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Funding

The US Immunodeficiency Network (USIDNET) is supported by a coopera agreement, U24AI86837, from the National Institute of Allergy and Infectious Diseases (NIAID). This study was not funded and authors were not compensated for their effort.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Columbia University Irving Medical Center, 622 W. 168th Street, PH-17, New York, NY, 10032, USA

    Deepti R. Deshpande & Jordan S. Orange

  2. Department of Medicine, University of California, Irvine, CA, USA

    Yesim Y. Demirdag

  3. Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital, Cincinnati, OH, USA

    Rebecca A. Marsh

  4. Division of Allergy and Immunology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Kathleen E. Sullivan

Authors
  1. Deepti R. Deshpande
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  2. Yesim Y. Demirdag
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  3. Rebecca A. Marsh
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  4. Kathleen E. Sullivan
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  5. Jordan S. Orange
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Consortia

The USIDNET Consortium

Contributions

Deepti R. Deshpande: Conceptualized the study, designed the work, conducted analysis, and interpretation of the data as well as drafted the manuscript and approved the final manuscript submitted.

Yesim Y. Demirdag: Revised the manuscript.

Kathleen E. Sullivan: Made substantial contributions to acquisition of data into the USIDNET registry and contributed to more than 10% of the patients in this manuscript and revised the manuscript.

Rebecca A Marsh: Made contributions to the conceptualizing of the study and revised the manuscript.

Jordan S. Orange: Revised the manuscript.

Corresponding author

Correspondence to Deepti R. Deshpande.

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Conflicts of Interest

Deepti R. Deshpande reports that she is employed by Regeneron Pharmaceuticals and her spouse is employed by Bristol Myers Squibb.

Kathleen E. Sullivan reports grants from the Immune Deficiency Foundation during the conduct of the study; reports personal fees from Elsevier, UpToDate, and Immune Deficiency Foundation outside the submitted work.

Jordan S. Orange reports personal fees from Enzyvant, CSL Behring, Grifols, ADMA Biologics, Gigagen, Takeda, and Sigilon outside the submitted work.

Yesim Y Demirdag and Rebecca A. Marsh report no conflict of interest.

Ethics Approval

Manuscript has been approved by the USIDNET Steering Committee.

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Deshpande, D.R., Demirdag, Y.Y., Marsh, R.A. et al. Relationship Between Severity of T Cell Lymphopenia and Immune Dysregulation in Patients with DiGeorge Syndrome (22q11.2 Deletions and/or Related TBX1 Mutations): a USIDNET Study. J Clin Immunol 41, 29–37 (2021). https://doi.org/10.1007/s10875-020-00854-y

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  • DOI: https://doi.org/10.1007/s10875-020-00854-y

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