The mechanism of a pullulan-conjugated antigen immunotherapy for japanese cedar pollenosis

为了降低杉木特异性免疫治疗（IT）的不良反应并提高其疗效，研制了一种普鲁兰偶联抗原（CS-560）。如果能够充分阐明IT的作用机制，并且能够安全、特异性地进行治疗，则应该重新考虑IT作为jc -花粉症的优越治疗方法。13例接受IT治疗的jc -花粉症患者与10例未接受IT治疗的患者进行了比较。所有患者随访2个花粉季节并记录过敏日记。采集花粉季节前和花粉季节前的外周血单核细胞（PBMC），用花粉提取物刺激外周血单核细胞。采用酶联免疫吸附法测定培养上清液中白细胞介素(IL)-4、IL-5和ifn - γ的浓度。根据过敏日记，我们证实了CS-560的临床疗效。信息技术显著降低了症状用药评分。IL-4和IL-5水平仅在IT组下降。然而，两组的ifn - γ水平没有变化。CS-560对jc花粉症的特异性it明显改变了PBMC细胞因子的产生。之后，我们观察了连续4年使用普鲁兰偶联抗原进行18个月免疫治疗的杉木授粉病患者。我们仔细研究了一些临床因素，包括症状、药物评分和患者个人评价。这些因素似乎呈正相关。血清特异性ige和血清特异性igg4的变化均与临床疗效无关。我们的结果表明，在体外抗原刺激下单核细胞产生IL-4和IL-5的变化可能是免疫治疗效果的一个很好的指标。

A pullulan-conjugated antigen (CS-560) has been developed to reduce the adverse effect and to enhance the effect for the Japanese cedar-specific Immunotherapy (IT). If the mechanism of IT can be fully elucidated and the treatment can be conducted safely and with specificity, IT should be reconsidered as a superior treatment for JC-pollenosis. Thirteen patients with JC-pollenosis who had received IT were compared to 10 patients without IT. All patients were followed through 2 pollen seasons with allergy diaries. Peripheral blood mononuclear cells (PBMC) were collected before IT and just before the pollen seasons, and those were stimulated with pollen extract. The concentration of Interleukin (IL)-4, IL-5 and IFN-gamma in the culture supernatants were determined using enzyme-linked immunosorbent assay. According to the allergy dairies, we confirmed the clinical efficacy of CS-560. The symptom medication scores were significantly decreased by IT. The level of IL-4 and IL-5 declined only in the IT group. However, the level of IFN-gamma did not change in both groups. Specific-IT for JC-pollenosis using CS-560 clearly modified cytokine production by PBMC. After that, we have observed Japanese cedar pollinosis patients who had taken by 18-months immunotherapy using pullulan-conjugated antigen for four consecutive years. We have carefully examined some clinical factors including the evaluation by symptom medication score and patients' personal evaluations. These factors seemed to be positively correlated. Neither the change in serum specific-IgE nor the change in serum specific-IgG4 was related to clinical efficacy. Our results suggested that the change in the production of IL-4 and IL-5 from mononuclear cells stimulated by antigen in vitro would be a good indicator of the efficacy of immunotherapy.