Rossi Renato E, Monasterolo Giorgio, Coco Giuseppe, Silvestro Luisa, Operti Daniela
Allergy Unit National Health Service, Rete di Allergologia Regione Piemonte, Cuneo, Italy.
Vaccine. 2007 Jan 15;25(5):957-64. doi: 10.1016/j.vaccine.2006.08.040. Epub 2006 Sep 11.
A number of reports suggest that induction of IgG 'blocking antibodies' may be important for successful allergen immunotherapy. Nevertheless, a significant increase in specific IgG and IgG4 antibodies has not been consistently demonstrated for sublingual immunotherapy (SLIT).
The present observation included three groups of grass pollen allergic patients all submitted to three different allergen immunotherapeutic regimens in an open, non-placebo controlled clinical study: (i) 16 patients underwent a modified 'cluster' regimen of weekly injections of a standardized aluminium-absorbed Phleum pratense extract for 5 weeks, followed by 3 weeks of maintenance injections. (ii) Fifteen patients were treated with standardized timothy grass pollen-allergen oral vaccine. In the first session of a SLIT protocol without up-dosing, each patient received 2.4 ml of sublingual vaccine containing about 57 microg of Phl p 5 and received a maintenance dose of 24 microg of Phl p 5 once a day for 120 days. (iii) Fourteen subjects were treated with a standardized allergen extract containing 5-grass pollen mixture; a SLIT protocol was performed without up-dosing, administering a dose corresponding to about 10.0 microg/ml grass-pollen Group 5 and a maintenance dose of 4 microg of grass-pollen Group 5 once a day for 135 days. Patients' sera were characterized in detail by determining IgG4 antibodies to rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4 and eosinophil cationic protein before the start of immunotherapy and during the peak of pollen season.
No relevant systemic side effects were registered in patients treated with the modified cluster subcutaneous immunotherapy (SCIT) protocol and the two SLIT protocols without build-up phase. After SCIT all patients had high titres of serum allergen-specific IgG4 antibodies. High-dose SLIT led to an IgG4 increase comprising 25% of the SCIT level, while low-dose SLIT increased to 4% of the SCIT. Furthermore, the increase of specific IgG antibodies corresponds to a decrease of serum ECP during allergen exposure.
These preliminary data seem to indicate that: (i) pre-seasonal high-dose SLIT protocol without build-up phase is safe and well-tolerated by allergic patients; (ii) compared to IgG4 levels induced by SCIT, only a high-dose SLIT regimen results in an appreciable serum specific IgG4 increase.
多项报告表明，诱导IgG“封闭抗体”可能对变应原免疫疗法的成功至关重要。然而，舌下免疫疗法（SLIT）中特异性IgG和IgG4抗体的显著增加尚未得到一致证实。
本观察纳入了三组草花粉过敏患者，在一项开放、非安慰剂对照的临床研究中，所有患者均接受三种不同的变应原免疫治疗方案：（i）16例患者接受改良的“集群”方案，每周注射标准化的氢氧化铝吸附草地早熟禾提取物，共5周，随后进行3周的维持注射。（ii）15例患者接受标准化的梯牧草花粉变应原口服疫苗治疗。在无剂量递增的SLIT方案的第一阶段，每位患者接受2.4 ml含约57 μg Phl p 5的舌下疫苗，并每天接受24 μg Phl p 5的维持剂量，持续治疗120天。（iii）14例受试者接受含5种草花粉混合物的标准化变应原提取物治疗；进行无剂量递增的SLIT方案，给予相当于约10.0 μg/ml草花粉第5组的剂量，以及每天4 μg草花粉第5组的维持剂量，持续治疗135天。在免疫治疗开始前和花粉季节高峰期，通过测定针对重组Phl p 1、2、5、6、7、11、12和天然Phl p 4的IgG4抗体以及嗜酸性粒细胞阳离子蛋白，对患者血清进行详细分析。
接受改良集群皮下免疫疗法（SCIT）方案和两种无剂量递增阶段的SLIT方案治疗的患者未出现相关的全身不良反应。SCIT治疗后，所有患者血清变应原特异性IgG4抗体滴度均较高。高剂量SLIT导致IgG4增加至SCIT水平 的25%，而低剂量SLIT增加至SCIT的4%。此外，特异性IgG抗体的增加与变应原暴露期间血清嗜酸性粒细胞阳离子蛋白（ECP）的降低相对应。
这些初步数据似乎表明：（i）无剂量递增阶段的季节性前高剂量SLIT方案对过敏患者是安全且耐受性良好的；（ii）与SCIT诱导的IgG4水平相比，只有高剂量SLIT方案能使血清特异性IgG4有明显增加。
