Manley G T, Smitt P S, Dalmau J, Posner J B
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Ann Neurol. 1995 Jul;38(1):102-10. doi: 10.1002/ana.410380117.
HuD, a human neuronal RNA-binding protein, was the first identified member of a family of antigens that also includes HuC and Hel-N1 (Hu antigens). The serum of all patients with anti-Hu-associated paraneoplastic encephalomyelitis and sensory neuronopathy react with HuD and Hel-N1, but the reactivity with HuC is unknown. In the current study we examined (1) the reactivity of anti-Hu sera with HuD, HuC, and Hel-N1; (2) the expression of HuD, HuC, and Hel-N1 messenger RNA in small-cell lung cancer of patients with and those without paraneoplastic encephalomyelitis/sensory neuronopathy; (3) the correlation between anti-Hu serum reactivity with these three Hu antigens and the type of neurological symptoms; and (4) the major immunogenic sites of HuD. Our findings indicate that all anti-Hu sera react with HuD, HuC, and Hel-N1. However, only HuD is expressed in the small-cell lung cancer tumors, indicating that among the three Hu antigens, HuD appears to play a central role in triggering the anti-Hu immune response. No differences were identified regarding the reactivity of the anti-Hu antibodies with HuD, HuC, and Hel-N1 and the spectrum of neurological symptoms presented by the patients. Study of the major immunogenic sites of HuD resulted in the identification of two major immunodominant regions with at least two distinct epitopes recognized by the serum of all patients with anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuronopathy.
HuD是一种人类神经元RNA结合蛋白，是一类抗原家族中首个被鉴定出的成员，该家族还包括HuC和Hel-N1（Hu抗原）。所有患有抗Hu相关副肿瘤性脑脊髓炎和感觉神经元病的患者血清均与HuD和Hel-N1发生反应，但与HuC的反应性尚不清楚。在本研究中，我们检测了：（1）抗Hu血清与HuD、HuC和Hel-N1的反应性；（2）患有和未患有副肿瘤性脑脊髓炎/感觉神经元病的患者的小细胞肺癌中HuD、HuC和Hel-N1信使RNA的表达；（3）抗Hu血清与这三种Hu抗原的反应性与神经症状类型之间的相关性；以及（4）HuD的主要免疫原性位点。我们的研究结果表明，所有抗Hu血清均与HuD、HuC和Hel-N1发生反应。然而，只有HuD在小细胞肺癌肿瘤中表达，这表明在这三种Hu抗原中，HuD似乎在触发抗Hu免疫反应中起核心作用。在抗Hu抗体与HuD、HuC和Hel-N1的反应性以及患者出现的神经症状谱方面未发现差异。对HuD主要免疫原性位点的研究确定了两个主要的免疫显性区域，至少有两个不同的表位可被所有患有抗Hu相关副肿瘤性脑脊髓炎/感觉神经元病的患者血清识别。
