Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms whereby HBV induces ALF are unknown. We used gene expression profiling to establish a molecular definition of hepatitis B virus (HBV)-associated ALF. Two patients who underwent liver transplantation for HBV-associated ALF were studied. Gene expression profiling was performed on 8 liver specimens obtained from the two patients with ALF (4 samples per liver) and individual liver specimens from 8 liver donors and normal livers from 11 patients who underwent resection for angioma. Statistical analyses were used to identify the signature genes of HBV-associated ALF. Multivariate permutation analysis identified 1,368 transcripts that were differentially expressed in ALF; 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. ALF was characterized by 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. Using phage display technology, we demonstrated that the molecular target of the massive intrahepatic antibody response is the hepatitis B core antigen (HBcAg). These data suggest that the humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF.
B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus-associated acute liver failure.
Specimen part
View SamplesWe provide direct in vivo evidence for activation of the BCR and canonical NF-KB pathways in MCL that, in the absence of activating mutations, is dependent on the lymph node microenvironment.
Pathogenic role of B-cell receptor signaling and canonical NF-κB activation in mantle cell lymphoma.
Specimen part
View SamplesWe provide direct in vivo evidence for activation of the BCR and canonical NF-KB pathways in MCL that, in the absence of activating mutations, is dependent on the lymph node microenvironment. This finding provides a mechanistic explanation for the surprising efficacy of ibrutinib for the treatment of this type of lymphoma. Mutations in components of the BCR and NF-KB pathways are associated with cell-autonomous signaling and resistance to ibrutinib. Overall design: Lymph node biopsies and peripheral blood samples were obtained from patients with previously untreated MCL.
Pathogenic role of B-cell receptor signaling and canonical NF-κB activation in mantle cell lymphoma.
No sample metadata fields
View SamplesBortezomib-induced resistant MCL cell lines (HBL2 BR and JEKO BR) were generated by continuous cultured of corresponding parental cell lines (HBL2 PT and JEKO PT) with increasing bortezomib concentrations
Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation.
Specimen part, Cell line
View SamplesTo elucidate effects of tumor host interactions in vivo in CLL, purified tumor cells were obtained concurrently from blood, bone marrow and/or lymph node and analyzed by gene expression profiling.
The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia.
Specimen part, Subject
View SamplesWe identified 18 patients with the distinct clinical phenotype of disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis and molds. This syndrome typically had its onset in adulthood and was characterized by profound circulating monocytopenia, B lymphocytopenia, and NK lymphocytopenia. T lymphocytes were variably affected. Despite these peripheral cytopenias, all patients had macrophages and plasma cells at sites of inflammation and normal immunoglobulin levels. This novel clinical syndrome links mycobacterial, viral, and fungal susceptibility with malignancy and is transmitted in an autosomal dominant pattern.
Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia.
Specimen part, Disease, Disease stage, Subject
View SamplesMacrophages, dendritic cells, conventional CD4+ T cells, CD8+ T cells, and regulatory T cells isolated from mouse colon cancer model MC38 tumors implanted subcutaneously to young (3 month) and aged (12 month) mice were sequenced using ImmGen's standard ultra-low input RNA-seq pipeline, in order to study age-dependent differences in intraltumoral immune cell functions and their impact on tumor control Overall design: Samples collected at the Center for Systems Biology at Mass General Hospital, shipped frozen to a central location, and sequenced using ImmGen's standard RNA-seq pipeline
Age-related tumor growth in mice is related to integrin α 4 in CD8+ T cells.
Age, Specimen part, Cell line, Subject
View SamplesAnopheles gambiae antennal and palpal transcriptome expression profiles (male and female)
Transcriptome profiling of chemosensory appendages in the malaria vector Anopheles gambiae reveals tissue- and sex-specific signatures of odor coding.
Sex, Specimen part, Cell line
View SamplesRNAseq from male testes
Odorant receptor-mediated sperm activation in disease vector mosquitoes.
Sex, Specimen part
View SamplesThis study characterizes the inflammatory processes in left-sided colitis, pancolitis, and UC-associated dysplasia at the transcriptional level in colonics biopsies in order to identify potential biomarkers and transcripts of importance for the carcinogenic behaviour of chronic inflammation
Transcriptional analysis of left-sided colitis, pancolitis, and ulcerative colitis-associated dysplasia.
Specimen part, Disease, Disease stage
View Samples