Dataset: B-Cell Gene Signature in HBV-Associated Acute Liver Failure
Background: The dramatic clinical course of acute liver failure has posed major limitations for pathogenesis studies. We used gene...
Background: The dramatic clinical course of acute liver failure has posed major limitations for pathogenesis studies. We used gene expression profiling to establish a molecular definition of hepatitis B virus (HBV)-associated acute liver failure. Methods: Two patients who underwent liver transplantation for HBV-associated acute liver failure were studied. Gene expression profiling was performed on 8 liver specimens obtained from the two patients with acute liver failure (4 samples per liver) and individual liver specimens from 8 liver donors. Statistical analyses were used to identify the signature genes of HBV-associated acute liver failure. Results: Multivariate permutation analysis identified 1,368 transcripts that were differentially expressed in acute liver failure; 709 were up-regulated and 659 down-regulated. The most represented up-regulated transcripts were those involved in the immune response, whereas the most abundant down-regulated transcripts were those involved in metabolism and hepatic synthesis. Acute liver failure was characterized by an overriding B-cell signature comprising genes related to mature B cells and plasma cells with abundant polyclonal expression of immunoglobulin genes. By contrast, there was a limited T-cell signature and up-regulation of several inhibitors of T-cell activation. Immunohistochemical analysis confirmed the prominent B-cell signature showing diffuse liver infiltration by plasma blasts and plasma cells with strong cytoplasmic staining for IgM and IgG, associated with a significant deposition of complement factors. Conclusions: The presence of a prominent intrahepatic plasma-cell infiltrate with ectopic immunoglobulin production and complement deposition suggests a pivotal role of humoral immunity in the pathogenesis of acute liver failure associated with HBV infection. Keywords: Expression prrofiling by array Liver samples were obtained from explanted livers of two patients with HBV-associated acute liver failure (4 samples per liver) and 8 individual normal liver donors and gene expression profiling was used to establish a molecular definition of acute liver failure.
- Dec.12, 2014
- Sep.11, 2014