Benyahia B, Liblau R, Merle-Béral H, Tourani J M, Dalmau J, Delattre J Y
Department of Neurology and INSERM U 495, Groupe Haspitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, France.
Ann Neurol. 1999 Feb;45(2):162-7. doi: 10.1002/1531-8249(199902)45:2<162::aid-ana5>3.0.co;2-r.
Paraneoplastic encephalomyelitis or subacute sensory neuronopathy associated with small-cell lung cancer (SCLC) and high titers of anti-HuD antibodies, also called the "anti-Hu syndrome," is believed to result from an immune response triggered by tumor antigens and misdirected to the neurons. To further assess the issue of cell-mediated immunity in this disease, the peripheral blood lymphocyte surface phenotype was studied in 15 patients suffering from the anti-Hu syndrome (seropositive group) and in two control groups consisting of 12 seronegative SCLC patients without neurological syndrome and 15 healthy volunteers. In addition, the recombinant human HuD protein was used to stimulate in vitro peripheral blood mononuclear cells of 10 seropositive patients and of 10 patients from each control group. Phenotypic analysis of the peripheral blood lymphocytes revealed a significant increase of the memory helper (CD45RO+CD4+) T cells in the seropositive group in comparison with the two control groups. Antigen-specific proliferation of peripheral blood mononuclear cells, measured by [3H]thymidine uptake after HuD antigen stimulation, was much higher in the seropositive group than in the two control groups, and phenotypic analysis of proliferating cells revealed a significant expansion of the CD45RO subpopulation of T cells in the seropositive group. Furthermore, after HuD stimulation, a significant increase of the interferon-gamma/interleukin-4 ratio was found in culture supernatants of the seropositive group compared with seronegative SCLC patients and normal controls. Taken together, these results indicate that HuD protein is an antigenic target for autoreactive CD4+ T cells, presumably of the Th1 subtype, which could therefore be directly involved in cell-mediated injury of the nervous system as well as in antitumoral immunity.
与小细胞肺癌（SCLC）及高滴度抗HuD抗体相关的副肿瘤性脑脊髓炎或亚急性感觉神经元病，也称为“抗Hu综合征”，被认为是由肿瘤抗原触发并错误导向神经元的免疫反应所致。为了进一步评估该疾病中细胞介导免疫的问题，对15例抗Hu综合征患者（血清阳性组）以及由12例无神经综合征的血清阴性SCLC患者和15名健康志愿者组成的两个对照组的外周血淋巴细胞表面表型进行了研究。此外，使用重组人HuD蛋白刺激10例血清阳性患者以及每个对照组的10例患者的体外外周血单个核细胞。外周血淋巴细胞的表型分析显示，与两个对照组相比，血清阳性组中记忆辅助（CD45RO + CD4 +）T细胞显著增加。通过HuD抗原刺激后[3H]胸苷摄取测量的外周血单个核细胞的抗原特异性增殖，血清阳性组比两个对照组高得多，并且增殖细胞的表型分析显示血清阳性组中T细胞的CD45RO亚群显著扩增。此外，与血清阴性SCLC患者和正常对照相比，HuD刺激后，血清阳性组培养上清液中干扰素-γ/白细胞介素-4比值显著增加。综上所述，这些结果表明HuD蛋白是自身反应性CD4 + T细胞（可能是Th1亚型）的抗原靶点，因此可能直接参与神经系统的细胞介导损伤以及抗肿瘤免疫。
