Th17-associated cytokines multiplex testing indicates the potential of macrophage inflammatory protein-3 alpha in the diagnosis of biliary atresia.

ABSTRACT

BACKGROUND & AIMS: Biliary atresia (BA) is a neonatal obliterative cholangiopathy with high prevalence in south China. Accurate identification of BA among infants with obstructive jaundice is still difficult by noninvasive diagnostic tools. Th17 cells have been reported closely related with the development of BA, which suggest that Th17-associated cytokines were potential biomarkers for the diagnosis of BA patients. METHODS: In the training study, 76 infants who were divided into 2 groups, including BA group (n = 31) and non-BA jaundice group (n = 45). Clinical and routine laboratory data were collected from all subjects. Totally 25 Th17-associated cytokines were tested and compared between groups. The diagnostic value of each differential cytokine was evaluated by the area under the receiver operating characteristic curve (AUC). The best potential diagnostic biomarker was further validated in a cohort including 68 jaundice infants from our partnering institution in a blinded fashion. RESULTS: Data from the training study showed that gamma-glutamyl transferase (GGT) and clay stool would be helpful in the identification of BA patients in jaundice subjects. Th17-associated cytokines assay indicated that IL-17F, IL-10, macrophage inflammatory protein-3alpha (MIP3a), IL-22, IL-13, IL-33, IL-6, IL-17E, IL-27, IL-31, TNF-a and TNF-b were differentially expressed in BA patients, and the AUC of MIP3a was higher than other markers. MIP3a alone or combined with other laboratory data would significantly increase the diagnostic accuracy of BA. The diagnostic value of MIP3a was further confirmed in our validation study. CONCLUSION: MIP3a alone or combined with other laboratory data would significantly increase the diagnostic accuracy of BA.