Immune Biomarkers at Birth Predict Lower Respiratory Tract Infection Risk in a Large Birth Cohort

Author:

Mondell Ethan1ORCID,Nino Gustavo23,Hong Xiumei4,Wang Xiaobin45ORCID,Gutierrez Maria J.6

Affiliation:

1. School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA

2. Division of Pulmonary and Sleep Medicine, Children’s National Hospital, George Washington University, Washington, DC 20010, USA

3. Center for Genetic Medicine Research, Children’s Research Institute, Washington, DC 20010, USA

4. Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA

5. Division of General Pediatrics and Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

6. Division of Pediatric Allergy, Immunology and Rheumatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

Abstract

Lower respiratory tract infections (LRTIs) remain the leading cause of infant morbidity and mortality worldwide and affect long-term respiratory health. Identifying immunological determinants of LRTI susceptibility may help stratify disease risk and identify therapies. This study aimed to identify neonatal immunological factors predicting LRTI risk in infancy. Cord blood plasma from 191 neonates from the Boston Birth Cohort was analyzed for 28 soluble immune factors. LRTI was defined as bronchiolitis, bronchitis, or pneumonia during the first year of life. Welch’s t-test demonstrated significantly higher log10 transformed concentrations of IL-17 and IFNγ in the LRTI group compared to neonates without LRTI in the first year of life (p < 0.05). Risk associations were determined using multivariate survival models. There were 29 infants with LRTIs. High cord blood levels of IFNγ (aHR = 2.35, 95% CI 1.07–5.17), TNF-β (aHR = 2.86, 95% CI 1.27–6.47), MIP-1α (aHR = 2.82, 95% CI 1.22–6.51), and MIP-1β (aHR = 2.34, 95% CI 1.05–5.20) were associated with a higher risk of LRTIs. RANTES was associated with a lower risk (aHR = 0.43, 95% CI 0.19–0.97). Soluble immune factors linked to antiviral immunity (IFNγ) and cytokines mediating inflammatory responses (TNF-β), and cell homing (MIP-1α/b), at birth were associated with an increased risk of LRTIs during infancy.

Funder

National Institutes of Health

Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Hu-man Services

Publisher

MDPI AG

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