Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Hodgkin Lymphoma Cell Lines and Tissues Express mGluR5: A Potential Link to Ophelia Syndrome and Paraneoplastic Neurological Disease

Sofia Schnell
ORCID logo ,
Ellen Knierim
,
Petra Bittigau
,
Jakob Kreye
,
Kathrin Hauptmann
ORCID logo ,
Patrick Hundsdoerfer
,
Susanne Morales-Gonzalez
,
Markus Schuelke
* ORCID logo ,
Marc Nikolaus
*
Version 1 : Received: 29 December 2022 / Approved: 4 January 2023 / Online: 4 January 2023 (08:47:37 CET)

A peer-reviewed article of this Preprint also exists.

Schnell, S.; Knierim, E.; Bittigau, P.; Kreye, J.; Hauptmann, K.; Hundsdoerfer, P.; Morales-Gonzalez, S.; Schuelke, M.; Nikolaus, M. Hodgkin Lymphoma Cell Lines and Tissues Express mGluR5: A Potential Link to Ophelia Syndrome and Paraneoplastic Neurological Disease. Cells 2023, 12, 606. Schnell, S.; Knierim, E.; Bittigau, P.; Kreye, J.; Hauptmann, K.; Hundsdoerfer, P.; Morales-Gonzalez, S.; Schuelke, M.; Nikolaus, M. Hodgkin Lymphoma Cell Lines and Tissues Express mGluR5: A Potential Link to Ophelia Syndrome and Paraneoplastic Neurological Disease. Cells 2023, 12, 606.

Abstract

Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and the presence of antibodies to the metabotropic glutamate 5 receptor (mGluR5). Little is known about the pathogenetic link between these symptoms and the role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with Ophelia syndrome and with isolated classical Hodgkin lymphoma by quantitative immunocytochemistry for mGluR5-expression. Further, we studied the L-1236, L-428, L-540, SUP-HD1, KM-H2, and HDLM-2 classical Hodgkin lymphoma cell lines by FACS and Western blot for mGluR5-expression, and by transcriptome analysis. mGluR5 surface expression differed significantly in terms of receptor density, distribution pattern, and percentage of positive cells. Highest expression levels were found in the L-1236 line. RNA-sequencing revealed more than 800 genes that were higher expressed in the L-1236 line in comparison to the other classical Hodgkin lymphoma cell lines. High mGluR5-expression was associated with upregulation of PI3K/AKT and MAPK pathways and of downstream targets (e.g. EGR1) known to be involved in classical Hodgkin lymphoma progression. Finally, mGluR5 expression was increased in the classical Hodgkin lymphoma-tissue of our Ophelia syndrome patient in contrast to five classical Hodgkin lymphoma-patients without autoimmune encephalitis. Given the association of encephalitis and classical Hodgkin lymphoma in Ophelia syndrome, it is possible that mGluR5-expression on classical Hodgkin lymphoma cells not only drives tumor progression but also triggers anti-mGluR5 encephalitis even before classical Hodgkin lymphoma becomes manifest.

Keywords

metabotropic glutamate 5 receptor; anti-mGluR5 encephalitis; neuroimmunology; pediatric neu-rology; pediatric oncology; transcriptome analysis; Hodgkin lymphoma; Ophelia syndrome

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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