Associations Between Multiple Immune-Response-Related Proteins and Neonatal Infection: A Proteomic Study Using Cord...

Neonates are highly susceptible to infection, a major cause of neonatal death, given their immature immune system. Comprehensive studies examining multiple immune-response-related proteins in relation to neonatal infection are scarce. We conducted a nested case-control study within the Shenzhen Baoan Birth and Twin (SZBBTwin) cohort, measuring 92 immune-response-related proteins in cord plasma of 149 twins (including 34 discordant twin pairs) with proximity extension assay. All twins were followed for clinical diagnoses of infection from birth until 27 days of age. Wilcoxon rank-sum test was used to determine differentially abundant proteins (DAPs) between infected and noninfected neonates, the predictive performance of which was evaluated by receiver operating characteristic curves, and their functions and pathways were annotated through enrichment analysis. Logistic regression was used to assess the associations between levels of proteins and risk of neonatal infection. Finally, five DAPs (ITGA11, FCRL6, DDX58, SH2D1A, and EDAR) were identified for neonatal infection, and the area under the curve of the five DAPs achieved 0.835 for infection prediction. Enrichment analysis indicated that five DAPs were mainly involved in immune function and cell binding, and they were mainly enriched in the nuclear factor kappa-B pathway. A higher level of ITGA11 was associated with an increased risk of neonatal infection in all twins (OR 3.00; 95% CI [1.33, 6.78]) and discordant twin pairs (OR 5.50; 95% CI [1.20, 25.23]). In conclusion, multiple immune-response-related proteins in cord plasma, particularly ITGA11, are associated with the risk of neonatal infection in twins.