Abstract
Background: Biliary atresia (BA) is considered to be an autoimmune-mediating inflammatory injury. The pathogenesis of BA has been proposed with the clonal transformation of T cells expressing analogous T-cell receptor β-chain variable regions (TRBVs).Methods: The TRBV profile of the peripheral blood mononuclear cells (PBMCs) in infants with BA and control infants (healthy donors, HDs), respectively, were characterized by using high-throughput sequencing (HTS). The diversity of T cells was analyzed based on the frequency of complementarity-determining region 3 (CDR3) or V(CDR3)J. Moreover, the correlation between absolute lymphocyte count (ALC) and lactate dehydrogenase (LDH) or diversity (clonality) indices, respectively, were analyzed for subjects with BA and HD.Results: The diversity indices of CDR3, V(CDR3)J in BA are lower than those in subjects with HD, in addition, there are significantly different levels of neutrophile, neutrophile/lymphocyte ratio (NLR), and LDH between groups of BA and HD. The correlation between ALC and diversity index is significant in subjects with HD but is not for subjects with BA. Conversely, the relationship between ALC and LDH is significant in subjects with BA but is not for subjects with HD. Moreover, 12 CDR3 motifs are deficient or lower expression in BA compared with that in the HD group.Conclusion: Our results demonstrate that the profile of TRBV repertoire is significantly different between subjects with BA and HD, and suggest that the immune imbalance and elevated LDH level are associated with the pathogenesis of BA. Moreover, the values of neutrophile, NLR, and LDH could be used for the differential diagnosis of BA.
Highlights
Biliary atresia (BA) is characterized by progressive, necroinflammatory, and fibrosis of the extra- and intrahepatic biliary system, leading to the bile flow obstruction, cholestasis, and jaundice in infants [1, 2]
Sato K et al suggested that the biliary epithelial cells were a physical barrier that drains the bile into the duodenum but they were immunocompetent cells involved in tissue homeostasis, which is capable of recognizing microbial conserved antigens through pattern recognition receptors (PRRs) and initiating an inflammatory response [6]
Approximately 5,622,653 total V(CDR3)J combinations were generated in BA samples, which was higher than that in healthy donors (HDs) (4,954,891, mean), but the difference was no significant difference (p = 0.1472, Figure 1A)
Summary
Biliary atresia (BA) is characterized by progressive, necroinflammatory, and fibrosis of the extra- and intrahepatic biliary system, leading to the bile flow obstruction, cholestasis, and jaundice in infants [1, 2]. Sato K et al suggested that the biliary epithelial cells (cholangiocytes) were a physical barrier that drains the bile into the duodenum but they were immunocompetent cells involved in tissue homeostasis, which is capable of recognizing microbial conserved antigens through pattern recognition receptors (PRRs) and initiating an inflammatory response [6]. Through the stimulation of specific antigens, the selective distribution of the T cell receptor (TCR, TR) spectrum could reflect the clonal amplification and functional changes of the Tcell population [10]. The analysis of the various characteristics of CDR3 can provide key clues for the study of the structure and function related to the different TRs recognizing specific antigens [11, 12]. The pathogenesis of BA has been proposed with the clonal transformation of T cells expressing analogous T-cell receptor β-chain variable regions (TRBVs)
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