Immunologic, Perinatal, and Postnatal Characteristics of Infants with Idiopathic T Cell Lymphopenia

Newborn screening (NBS) measures T cell receptor excision circle (TREC) counts in infants to identify infants with potential primary immunodeficiency. Low TREC counts are associated with T cell lymphopenia (TCL). Infants are considered to have idiopathic TCL if no cause for the lymphopenia is found. By convention, infants whose T cell counts normalize within 12 months of birth are considered to have transient TCL. This study aimed to characterize and differentiate infants with transient and persistent idiopathic TCL across demographic, immunologic, perinatal, and postnatal factors. There were 53 infants referred to an academic medical center for idiopathic TCL between September 2010 and August 2021, following abnormal NBS at a gestational age of at least 37 weeks. They were evaluated for CD3+, CD4+, and CD8+ T cell counts. Demographic, immunologic, perinatal, and postnatal data were collected from the electronic health record. Chi-square analysis was performed for mode of delivery, neonatal intensive care unit (NICU) stay, and hospitalization within 12 months of birth. Descriptive statistics were calculated and Mann-Whitney tests performed for assessing initial TREC counts, initial T cell counts, and birth weight by gestational age percentile. Of the 53 infants evaluated, 28 had transient while 25 had persistent idiopathic TCL. The transient cohort was 60.7% male and 28.6% African-American, and 35.7% had Medicaid. The persistent cohort was 60.0% male and 32.0% African-American, and 56.0% had Medicaid. The cohorts did not differ by mode of delivery (χ2(1,N = 52) = 3.71, p = 0.054), NICU stay (χ2(1,N = 51) = 0.11, p = 0.735), or postnatal hospitalization (χ2(1, N = 49) = 0.82, p = 0.365). Persistent lymphopenic infants had significantly lower median CD3+ (1176 vs. 2144 cells/µL; p < 0.001), CD4+ (866 vs. 1460 cells/µL; p < 0.001), and CD8+ (293 vs. 539 cells/µL; p = 0.003) counts than transient lymphopenic infants, but did not differ by median TREC count (73 vs. 52 TRECs/µL; p = 0.219) or birth weight percentile (41st vs. 20th percentile; p = 0.363). In our cohort, persistent idiopathic TCL infants had lower initial T cell counts than transient infants. None of the other factors differed between the groups. Future research should evaluate for differences across other relevant factors, including maternal health factors and other relevant perinatal and postnatal factors.