Using an oligonucleotide hybridization assay, we studied the clinical implication of wild-type hepatitis B virus (HBV) and a HBV mutant that is unable to secrete hepatitis B e antigen (HBeAg) because of a translational defect due to a stop codon in the pre-C region in 106 hepatitis B surface antigen-positive patients with chronic hepatitis B. Wild-type HBV was detected in 31 of42 (73.8%) HBeAg-positive patients, whereas a mixed viral population was present in 10 (23.8%). Significant differences in the severity and outcome of liver disease were not observed in the two groups of patients. However, the emergence of HBeAg-minus HBV in wild-type HBV carriers was associated with an exacerbation of liver disease and was followed by the presence of antibodies against HBeAg (anti-HBe) in serum in 50% of the cases. In 61 of 64 (95.3%) anti-HBe-positive patients, HBeAg-minus HBV was the predominant virus: HBeAg-minus HBV was detected in 42 patients (65.6%), whereas both wild-type and HBeAg-minus HBV were present in 19 (29.7%). HBeAg-minus HBV was associated with a course of hepatitis characterized by flare-ups of liver cell necrosis interspersed with periods of asymptomatic HBV carriage (P < 0.01). These data support the hypothesis that genetic heterogeneity of HBV significantly influences the course and outcome of chronic hepatitis B. Wild-type HBV secreting HBeAg induces immunologic tolerance and causes chronic infection. HBeAg-minus HBV might be unable to induce chronic infection without the helper function of wildtype HBV, but it appears to be more pathogenic. Once chronic infection is established, HBeAg-minus HBV variants may prevail and displace wild-type virus.Hepatitis B e antigen (HBeAg) is a partially degraded nonparticulate form of hepatitis B nucleocapsid protein secreted into the serum during florid hepatitis B virus (HBV) infection (1-3). HBeAg and polypeptides composing the viral nucleocapsid result from translation of a single open reading frame (C gene) containing two start codons, which identify pre-C and C regions (1-3). Initiation of translation from the first codon (pre-C) yields a secretory protein (HBeAg) with a signal peptide cleaved off during maturation (1-3). In carriers of HBV, disappearance of HBeAg and the presence of antibodies against HBeAg (anti-HBe) in serum is associated with clearance of HBV DNA from serum, hepatitis B core antigen from liver, and the resolution of histological activity (4,5). In areas with high or intermediate HBV endemicity, viral replication and liver damage persist in about 10% of anti-HBe-positive carriers (6-12). HBV mutants unable to secrete HBeAg because of translational defects in the pre-C region have been isolated in these patients (13)(14)(15)(16)(17)(18)(19)(20)(21). In the great majority of them (>90%), an unusual HBV strain was characterized with a G -* A mutation at nucleotide 1896, which generates a stop codon in the pre-C sequence (13-21).In our area, an additional mutation (G --A) at position 1899 was consistently associated with the stop codon...
Background: The prognostic value of changes in paraprotein markers after stem cell transplantation is unknown. We evaluated disease response using serum immunofixation (s-IFIX), total κ and λ ratio (KLR), and free light chain (FLC) ratio in myeloma patients who underwent autologous or autologous plus allogeneic stem cell transplantation. Methods: We studied s-IFIX, KLR, and FLC ratio in sera from 203 patients, 3 months after transplantation. We evaluated overall and event-free survival (OS and EFS, interval between date of study enrollment and date of death from any cause or date of progression, relapse, or death from any cause, respectively) by the Kaplan–Meier method. Results: Of the 203 patients, 51 were negative by s-IFIX, 99 reached a normal KLR, and 92 had a normal FLC ratio. Of the 51 patients with negative s-IFIX, 40 (78%) also had a normal FLC ratio. The median duration of OS was 54.3 months, and the median EFS was 19.5 months. None of the measured paraprotein parameters showed an association with OS. Only a normal KLR was associated with prolonged EFS (P = 0.016). Even a negative s-IFIX associated with a normal FLC ratio did not show a significant difference in terms of EFS and OS. Conclusions: Our analysis with a small cohort of patients did not show a significant impact of achieving complete response (CR) or stringent CR on patient survival.
Amyloidosis comprises a spectrum of disorders characterized by the extracellular deposition of amorphous material, originating from an abnormal serum protein. The typing of amyloid into its many variants represents a pivotal step for a correct patient management. Several methods are currently used, including mass spectrometry, immunofluorescence, immunohistochemistry, and immunogold labeling. The aim of the present study was to investigate the accuracy and reliability of immunohistochemistry by means of a recently developed amyloid antibody panel applicable on fixed paraffin-embedded tissues in an automated platform. Patients with clinically and pathologically proven amyloidosis were divided into two cohorts: a pilot one, which included selected amyloidosis cases from 2009 to 2018, and a retrospective one (comprising all consecutive amyloidosis cases analyzed between November 2018 and May 2020). The above-referred panel of antibodies for amyloid classification was tested in all cases using an automated immunohistochemistry platform. When fresh-frozen material was available, immunofluorescence was also performed. Among 130 patients, a total of 143 samples from different organs was investigated. They corresponded to 51 patients from the pilot cohort and 79 ones from the retrospective cohort. In 82 cases (63%), fresh-frozen tissue was tested by immunofluorescence, serving to define amyloid subtype only in 30 of them (36.6%). On the contrary, the automated immunohistochemistry procedure using the above-referred new antibodies allowed to establish the amyloid type in all 130 cases (100%). These included: ALλ (n = 60, 46.2%), ATTR (n = 29, 22.3%), AA (n = 19, 14.6%), ALκ (n = 18, 13.8%), ALys (n = 2, 1.5%), and Aβ2M amyloidosis (n = 2, 1.5%). The present immunohistochemistry antibody panel represents a sensitive, reliable, fast, and low-cost method for amyloid typing. Since immunohistochemistry is available in most pathology laboratories, it may become the new gold standard for amyloidosis classification, either used alone or combined with mass spectrometry in selected cases.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.