Evidence map›Paper›PMID 39082968›Full record

ArticleHepatology communications2024

B cells expressing mutated IGHV1-69-encoded antigen receptors related to virus neutralization show lymphoma-like transcriptomes in patients with chronic HCV infection.

Christoph Schultheiß, Edith Willscher, Lisa Paschold, Christin Ackermann, Moritz Escher, Rebekka Scholz, Maximilian Knapp, Jana Lützkendorf, Lutz P Müller, Julian Schulze Zur Wiesch and 1 more

Abstract read
In one paragraph

Article in Hepatology communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Christoph SchultheißDivison of Medical Oncology, University Hospital Basel, Basel, Switzerland.ORCID 0000-0001-9789-5776
Edith WillscherInternal Medicine IV, Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.ORCID 0000-0002-8786-4578
Lisa PascholdInternal Medicine IV, Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.ORCID 0000-0003-0020-1315
Christin AckermannInfectious Disease Unit, I, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Moritz EscherInternal Medicine IV, Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Rebekka ScholzInternal Medicine IV, Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.ORCID 0000-0003-2077-0718
Maximilian KnappInfectious Disease Unit, I, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0002-9554-5067
Jana LützkendorfInternal Medicine IV, Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.ORCID 0000-0002-5781-9266
Lutz P MüllerInternal Medicine IV, Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.ORCID 0000-0002-2212-8166
Julian Schulze Zur WieschInfectious Disease Unit, I, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0002-5033-1938
Mascha BinderDivison of Medical Oncology, University Hospital Basel, Basel, Switzerland.ORCID 0000-0003-0663-3004

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic HCV infection leads to a complex interplay with adaptive immune cells that may result in B cell dyscrasias like cryoglobulinemia or lymphoma. While direct-acting antiviral therapy has decreased the incidence of severe liver damage, its effect on extrahepatic HCV manifestations such as B cell dyscrasias is still unclear.

methodsWe sequenced B cell receptor (BCR) repertoires in patients with chronic HCV mono-infection and patients with HCV with a sustained virological response (SVR) after direct-acting antiviral therapy. This data set was mined for highly neutralizing HCV antibodies and compared to a diffuse large B cell lymphoma data set. The TKO model was used to test the signaling strength of selected B-BCRs in vitro. Single-cell RNA sequencing of chronic HCV and HCV SVR samples was performed to analyze the transcriptome of B cells with HCV-neutralizing antigen receptors.

resultsWe identified a B cell fingerprint with high richness and somatic hypermutation in patients with chronic HCV and SVR. Convergence to specific immunoglobulin genes produced high-connectivity complementarity-determining region 3 networks. In addition, we observed that IGHV1-69 CDR1 and FR3 mutations characterizing highly neutralizing HCV antibodies corresponded to recurrent point mutations found in clonotypic BCRs of high-grade lymphomas. These BCRs did not show autonomous signaling but a lower activation threshold in an in vitro cell model for the assessment of BCR signaling strength. Single-cell RNA sequencing revealed that B cells carrying these point mutations showed a persisting oncogenic transcriptome signature with dysregulation in signaling nodes such as CARD11, MALT1, RelB, MAPK, and NFAT.

conclusionsWe provide evidence that lymphoma-like cells derive from the anti-HCV immune response. In many patients, these cells persist for years after SVR and can be interpreted as a mechanistic basis for HCV-related B cell dyscrasias and increased lymphoma risk even beyond viral elimination.

Indexed as

B-LymphocytesHepacivirusHepatitis C, ChronicReceptors, Antigen, B-CellTranscriptomeAntibodies, NeutralizingAntiviral AgentsComplementarity Determining RegionsFemaleHumansLymphoma, Large B-Cell, DiffuseMaleMiddle AgedMutationSustained Virologic ResponseAntibodies, NeutralizingAntiviral AgentsComplementarity Determining RegionsReceptors, Antigen, B-Cell

Identifiers

PMID39082968
PMCPMC12333805

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.