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 ofGRM5transcripts 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.
针对神经元抗原代谢型谷氨酸受体5(mGluR5)的自身抗体已在奥菲莉亚综合征患者中被发现,该综合征表现为副肿瘤性边缘叶脑炎与霍奇金淋巴瘤(HL)的共发。目前关于mGluR5在HL中的表达频率、功能及其导致血清阳性副肿瘤疾病的潜在作用尚缺乏数据。我们采用免疫组织化学与荧光染色技术,对一组具有代表性的儿童HL及NHL患者队列(n=57)进行mGluR5表达研究。所有淋巴瘤组织均显示mGluR5阳性染色,且主要集中于霍奇金-里德-斯特恩伯格(H-RS)细胞。在无肿瘤的淋巴结组织中未检测到mGluR5染色,这与非恶性B细胞和T细胞的RNA测序数据中缺乏GRM5转录本的结果一致。儿童淋巴瘤中mGluR5的普遍存在,与其他恶性肿瘤中mGluR5表达及肿瘤进展相关的报道相符。我们重点针对疾病进展与神经系统症状,检测了其与临床特征的相关性。H-RS细胞中低mGluR5表达与患者低龄(<15岁)及EBV感染阳性组织学特征相关。副肿瘤性或神经系统症状仅见于HL患者。虽然mGluR5对HL严重程度可能存在影响,但其表达水平的预后价值仍需进一步研究。