Malling H J, Djurup R
Medical Department TTA, State University Hospital, Copenhagen, Denmark.
Allergy. 1988 Jan;43(1):60-70. doi: 10.1111/j.1398-9995.1988.tb02045.x.
The IgG subclass response was evaluated by a sensitive allergen- and subclass-specific solid phase immunoradiometric assay during a 1-year placebo-controlled, double-blind study of immunotherapy with Cladosporium herbarum in 22 adult asthmatics. The IgG response was mainly restricted to subclasses 1 and 4 but a few patients were IgG2 and IgG3 responders. An intense and early IgG1 response was observed during the first clusters of injection followed by a levelling down of the titer. The IgG4 response had a later onset and showed slowly increasing levels during the 12 months of immunotherapy. The graded clinical efficacy estimated by symptom-medication score was significantly correlated to the preseasonal IgG1 value, with high values indicating a deleterious response of immunotherapy (deterioration of disease activity). Likewise, the fold increase of IgG1 and IgG4 after two clusters of immunotherapy (i.e. after 4 weeks) was significantly related to the clinical outcome. Little or no increase of IgG1 and IgG4 was associated with improvement, i.e. decrease in symptom-medication score. The magnitude of the IgG1 response during the dose-increase phase was directly correlated to the number of systemic side effects. No relation of IgG1, IgG4 or IgG4/IgG1 ratio to changes in the IgE-mediated parameters (skin prick test, bronchial challenge and circulating specific IgE) was observed. Our data, which are based on few patients and only one allergen system, do not support the hypothesis of IgG acting as blocking antibody being the immunologic mechanism of immunotherapy. The association between high IgG4 values and a deleterious efficacy of immunotherapy might be caused by IgG4 acting as sensitizing antibodies. This explanation, however, is opposed by the lack of relation to systemic side effects.
在一项为期1年的安慰剂对照、双盲研究中，对22名成年哮喘患者进行了用草本枝孢菌进行免疫治疗的研究，期间通过一种灵敏的、针对变应原和亚类特异性的固相免疫放射分析来评估IgG亚类反应。IgG反应主要局限于亚类1和4，但有少数患者是IgG2和IgG3反应者。在最初几组注射期间观察到强烈且早期的IgG1反应，随后效价下降。IgG4反应出现较晚，在免疫治疗的12个月期间水平缓慢上升。通过症状-药物评分评估的分级临床疗效与季前IgG1值显著相关，高值表明免疫治疗的有害反应（疾病活动恶化）。同样，两组免疫治疗（即4周后）后IgG1和IgG4的增加倍数与临床结果显著相关。IgG1和IgG4很少增加或没有增加与症状改善相关，即症状-药物评分降低。剂量增加阶段IgG1反应的幅度与全身副作用的数量直接相关。未观察到IgG1、IgG4或IgG4/IgG1比值与IgE介导参数（皮肤点刺试验、支气管激发试验和循环特异性IgE）变化之间的关系。我们的数据基于少数患者且仅一个变应原系统，不支持IgG作为封闭抗体是免疫治疗免疫机制的假设。高IgG4值与免疫治疗有害疗效之间的关联可能是由于IgG4作为致敏抗体所致。然而，这种解释与缺乏与全身副作用的关系相矛盾。
