Relationship Between Severity of T Cell Lymphopenia and Immune Dysregulation in Patients with DiGeorge Syndrome (22q11.2
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ORIGINAL ARTICLE
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 Deepti R. Deshpande 1 USIDNET Consortium
&
Yesim Y. Demirdag 2 & Rebecca A. Marsh 3 & Kathleen E. Sullivan 4 & Jordan S. Orange 1 & The
Received: 16 June 2020 / Accepted: 24 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords 22q11.2 . DiGeorge syndrome . lymphopenia . autoimmunity . asthma . infections
Introduction DiGeorge syndrome (DGS) due to deletion of chromosome 22q11.2 is the most common microdeletion syndrome in
* Deepti R. Deshpande [email protected]; [email protected] 1
Department of Pediatrics, Columbia University Irving Medical Center, 622 W. 168th Street, PH-17, New York, NY 10032, USA
2
Department of Medicine, University of California, Irvine, CA, USA
3
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital, Cincinnati, OH, USA
4
Division of Allergy and Immunology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
humans, occurring with a frequency of about 1:4000 births, although higher frequencies were noted in fetuses in two pre
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