Associations between multiple immune-response-related proteins and neonatal infection: a proximity extension assay based proteomic study in cord plasma of twins

BackgroundGiven their immature immune system, neonates are highly susceptible to infection, a major cause of neonatal death. However, associations between immune-response-related proteins and risk of neonatal infection have yet been systematically investigated. MethodsWe conducted a nested case-control study of 149 twins (60 cases and 89 controls, including 34 pairs of discordant twins), within the Shenzhen Baoan Birth and Twin (SZBBTwin) cohort. Using proximity extension assay of Olink Proteomics, 92 immune-response-related proteins were measured in samples of cord plasma. All twins were followed for a diagnosis of infection from birth until 27 days of age. Wilcoxon rank-sum test was used to determine differentially expressed proteins (DEPs), and multivariable logistic regression was used to assess the associations of the levels of proteins with neonatal infection. The receiver operating characteristic curve was plotted to evaluate the predictive performance of DEPs. Enrichment analysis was performed to annotate potential functions and pathways of DEPs. ResultsFive DEPs (ITGA11, FCRL6, DDX58, SH2D1A, and EDAR) were identified for neonatal infection. A higher cord plasma level of integrin alpha 11 (ITGA11) was associated with a higher risk of neonatal infection in both the analyses of all twins and discordant twins. The area under the curve achieved 0.835 for the five DEPs. The identified DEPs were mainly involved in immune function and protein binding, and most of them were enriched in the nuclear factor kappa-B pathway. ConclusionMultiple immune-response-related proteins in cord plasma, particularly ITGA11, are associated with the risk of neonatal infection. Key pointIn this nested case-control study, 92 immune-response-related proteins were measured in cord plasma by proximity extension assay. A higher level of ITGA11 was associated with a higher risk of neonatal infection, in the analyses of all twins and discordant twins.