Proteomics defines plasma biomarkers for the early diagnosis of biliary atresia

Early diagnosis of biliary atresia (BA) is crucial for improving the chances of survival and preserving the liver function of children with BA. To explore potential biomarkers for early diagnosis of BA with other non-BA jaundice cases, we performed proteomic analysis with data-independent acquisition (DIA) and parallel reaction monitoring (PRM). With this approach we were able to detect and validate differential protein expression in plasma of patients. Bioinformatics analysis revealed the enrichment biological processes, characteristic of BA by identifying differential expression of specific proteins of which with 10 were up- and 23 down-regulated. Signaling pathway analysis demonstrated changes in protein expression associated with an alteration in immunoglobins levels, which is indicative immune dysfunction in BA. When polymeric immunoglobulin receptor (pIgR) expression was combined with an immunoglobulin lambda variable chain (IGL c2225_light_IGLV1-47_IGLJ2), revealed by machine learning, they provided a useful early diagnostic model for BA, which had a sensitivity of 0.8, specificity of 1, accuracy of 0.89, and AUC value of 0.944. Our study not only identified a possible effective plasma biomarker for the early diagnosis of BA but may also help to further elucidate the underlying mechanisms of BA.