Expression of mGluR5 in Pediatric Hodgkin and Non-Hodgkin lymphoma—A Comparative Analysis of Immunohistochemical and Clinical Findings Regarding the Association between Tumor and Paraneoplastic Neurological Disease

Abstract

Autoantibodies targeting the neuronal antigen metabotropic glutamate receptor 5 (mGluR5) have been identified in patients with Ophelia syndrome, which describes a co-occurrence of paraneoplastic limbic encephalitis and Hodgkin lymphoma (HL). Little data exist regarding frequency and function of mGluR5 in HL and its potential role in causing seropositive paraneoplastic disease. We studied a representative cohort of pediatric HL and NHL patients (n = 57) using immunohistochemistry and fluorescence staining to investigate mGluR5 expression. All lymphoma tissues displayed positive mGluR5 staining, with focus on Hodgkin–Reed–Sternberg (H-RS) cells. We did not detect any mGluR5 staining in tumor-free lymph nodes, which is consistent with the absence of GRM5 transcripts in RNA-sequencing data from non-malignant B and T cells. The frequent presence in pediatric lymphoma falls in line with reports of mGluR5 expression and associated tumor progression in other malignancies. We tested for correlation with clinical features, focusing on disease progression and neurological symptoms. Low mGluR5 expression in H-RS cells correlated with young patient age (<15 years) and positive histology for EBV infection. Paraneoplastic or neurological symptoms were found exclusively in HL patients. While an impact of mGluR5 on HL severity remains possible, a prognostic value of mGluR5 expression levels requires further investigation.

Keywords

• pediatric Hodgkin lymphoma
• autoimmune encephalitis
• Ophelia syndrome
• mGluR5
• paraneoplastic neurological syndromes
• EBV-positive HL