T–Cell Receptor Excision Circles in HIV–Exposed, Uninfected Newborns Measured During a National Newborn Screening Program for Severe Combined Immunodeficiency

Abstract

To assess the level of T-cell receptor excision circles (TRECs) in HIV-exposed, uninfected (HEU) infants as well as assess the variables associated with lower TRECs in the study population.Researchers in the study reported on 158 HEU infants born to mothers positive for HIV who were ≥32 weeks’ gestational age between January 2015 and July 2016 from 10 birthing centers in France.The study used the data from 2 separate French national studies from 10 birthing centers. The 2 studies included The French Perinatal Survey of the National Agency for Research on AIDS (EPF Study) (a national epidemiological cohort study of pregnant women positive for HIV and their infants) and the DEPISTREC Study (a national study of TRECs for newborn screening for all infants born in France). TRECs are byproducts made during T-cell development; thus, decreased levels of TRECS suggest a T-cell immunodeficiency. HEU infants were compared with nonexposed, healthy infants from the DEPISTREC Study.The demographics of the 158 infants’ mothers identified (who participated in both the EPF and DEPISTREC studies) were similar to all mothers included in the DEPISTREC Study at the time of analysis. Overall, TREC levels for the HEU infants were lower at 94 copies (range: 54–150) per microliter compared with the TREC levels of the infants not exposed to HIV perinatally (113 copies [range: 76–169] per microliter; P = .001). The study population was separated into 2 groups on the basis of origin ([1] sub-Saharan African or Caribbean decent and [2] other origins) and then individually compared with seronegative mothers in the DEPISTREC cohort. The 126 infants with sub-Saharan African or Caribbean decent had significantly lower TREC levels than the infants with seronegative mothers, whereas the 32 infants of other origin had no significant difference in TREC levels when compared with the infants with seronegative mothers.Researchers in the study concluded that when controlling for gestational age, overall, the HEU newborns had a lower TREC level than unexposed infants. They were unable to determine if control of maternal HIV viral replication had any effect on HEU infant TREC level. This study also noted that infants with sub-Saharan African or Caribbean decent had a significantly lower TREC level when compared with both HEU infants of other origin and the infants with seronegative mothers in the DEPISTREC study. Importantly, a previous study completed on New York State severe combined immunodeficiency disease and T-cell immunodeficiency newborn screening showed that infants of African American decent had lower TREC levels than infants of other origins in the general population.This study used the newborn screening program for severe combined immunodeficiency disease and T-cell immunodeficiency to assess the level of TRECs in HEU infants. When the study cohort was separated on the basis of origin, HEU infants of sub-Saharan African or Caribbean decent had a significantly lower TREC level than HEU infants of other origins. This suggests that patients with African descent may have lower TREC levels, in general, irrespective of HEU status.