Rare But Specific B‐Cell Receptor Reactivity Against Coxsackievirus A24 in Primary Central Nervous System Lymphomas
5 affiliations
- 1José Carreras Center for Immuno‐ and Gene Therapy of Department of Internal Medicine I, Hematology, Oncology, Rheumatology and Clinical Immunology Saarland University Medical School Homburg Germany
- 2Institute of Virology Saarland University Medical Center Homburg Germany
- 3Institute of Pathology University Hospital Essen Essen Germany
- 4Institute of Pathology and Neuropathology University Hospital Tübingen Tübingen Germany
- 5Department of Medicine I Medical Center Faculty of Medicine University of Freiburg Freiburg Germany
Abstract
Introduction Primary central nervous system lymphoma (PCNSL) remains a distinct and aggressive malignancy whose underlying antigenic triggers are largely unknown. While autoantigens such as neurabin‐I and SAMD14 have been implicated, the potential role of infectious agents in driving clonal B‐cell receptor selection within the central nervous system remains less understood. Methods A viral proteome microarray screening approach encompassing 158 viral entities was utilized to test tumor‐derived recombinant B‐cell receptors from PCNSL. Furthermore, we analyzed a validation cohort comprising 22 PCNSL patients and tested expanded control sera from 188 healthy individuals. Functional assays were performed to confirm B‐cell receptor activation and downstream signaling upon cognate antigen engagement. Results Screening identified a distinct B‐cell receptor reactivity directed against Coxsackievirus A24 in a PCNSL case, which was completely absent across non‐PCNSL lymphomas. Validation testing in an independent cohort confirmed rare reactivity (1/22, 4.55%). Control serum analysis revealed weak reactivity in 1 out of 188 healthy individuals (0.53%). Functional assays demonstrated that the Coxsackievirus A24‐derived antigen is capable of triggering antigen‐specific receptor signaling. Conclusion We report the first evidence linking PCNSL B‐cell receptor reactivity to a viral antigen, identifying Coxsackievirus A24 as a rare ligand. While functional assays confirm the capacity for receptor activation, the findings must be interpreted cautiously as hypothesis‐generating. Further investigation in larger independent cohorts is required to determine whether viral antigens play any meaningful pathogenic role in this malignancy. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.
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BibTeX
@article{kos2026rare,
title = {{Rare But Specific B‐Cell Receptor Reactivity Against Coxsackievirus A24 in Primary Central Nervous System Lymphomas}},
author = {Igor Age Kos and Onur Cetin and Natalie Fadle and Evi Regitz and Klaus‐Dieter Preuss and Stefan Lohse and Sigrun Smola and Sylvia Hartmann and Falko Fend and Karin Klingel and Florian Scherer and Elisabeth Schorb and Moritz Bewarder and Philipp Staber and Lorenz Thurner},
journal = {eJHaem},
year = {2026},
month = oct,
doi = {10.1002/jha2.70422},
url = {https://doi.org/10.1002/jha2.70422},
note = {CC BY},
}
RIS
TY - JOUR
TI - Rare But Specific B‐Cell Receptor Reactivity Against Coxsackievirus A24 in Primary Central Nervous System Lymphomas
AU - Igor Age Kos
AU - Onur Cetin
AU - Natalie Fadle
AU - Evi Regitz
AU - Klaus‐Dieter Preuss
AU - Stefan Lohse
AU - Sigrun Smola
AU - Sylvia Hartmann
AU - Falko Fend
AU - Karin Klingel
AU - Florian Scherer
AU - Elisabeth Schorb
AU - Moritz Bewarder
AU - Philipp Staber
AU - Lorenz Thurner
PY - 2026
DA - 2026/10/27
JO - eJHaem
DO - 10.1002/jha2.70422
UR - https://doi.org/10.1002/jha2.70422
AB - Introduction Primary central nervous system lymphoma (PCNSL) remains a distinct and aggressive malignancy whose underlying antigenic triggers are largely unknown. While autoantigens such as neurabin‐I and SAMD14 have been implicated, the potential role of infectious agents in driving clonal B‐cell receptor selection within the central nervous system remains less understood. Methods A viral proteome microarray screening approach encompassing 158 viral entities was utilized to test tumor‐derived recombinant B‐cell receptors from PCNSL. Furthermore, we analyzed a validation cohort comprising 22 PCNSL patients and tested expanded control sera from 188 healthy individuals. Functional assays were performed to confirm B‐cell receptor activation and downstream signaling upon cognate antigen engagement. Results Screening identified a distinct B‐cell receptor reactivity directed against Coxsackievirus A24 in a PCNSL case, which was completely absent across non‐PCNSL lymphomas. Validation testing in an independent cohort confirmed rare reactivity (1/22, 4.55%). Control serum analysis revealed weak reactivity in 1 out of 188 healthy individuals (0.53%). Functional assays demonstrated that the Coxsackievirus A24‐derived antigen is capable of triggering antigen‐specific receptor signaling. Conclusion We report the first evidence linking PCNSL B‐cell receptor reactivity to a viral antigen, identifying Coxsackievirus A24 as a rare ligand. While functional assays confirm the capacity for receptor activation, the findings must be interpreted cautiously as hypothesis‐generating. Further investigation in larger independent cohorts is required to determine whether viral antigens play any meaningful pathogenic role in this malignancy. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.
SN - 2688-6146
ER -