Jones M, Jeal H, Schofield S, Harris J M, Shamji M H, Francis J N, Durham S R, Cullinan P
Department of Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, part of the Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, London, UK.
Occup Environ Med. 2014 Sep;71(9):619-23. doi: 10.1136/oemed-2014-102119. Epub 2014 Jun 18.
The relationship between exposure to rodent allergens and laboratory animal allergy is complex; at highest allergen exposures there is an attenuation of sensitisation and symptoms which are associated with increased levels of rat-specific immunoglobulin (Ig)G and IgG4 antibodies. We set out to examine whether the increased levels of rat-specific IgG and IgG4 antibodies that we have previously observed at high allergen exposure in our cohort of laboratory animal workers play a functional role through blockage of the binding of IgE-allergen complex binding to CD23 receptors on B cells.
Cross-sectional survey of laboratory animal workers (n=776) in six UK pharmaceutical companies were surveyed. IgE-allergen complex binding to B cells was measured in 703 (97.9%) eligible employees; their exposure was categorised by either job group or number of rats handled daily.
We observed a significant decrease in IgE-allergen complex binding to B cells with increasing quartiles of both rat-specific IgG and IgG4 antibodies (p<0.001). IgE-allergen complex binding to B cells was lower in workers with high allergen exposure, and significantly so (p=0.033) in the subgroup with highest exposures but no work-related chest symptoms.
These findings demonstrate a functional role for rat-specific IgG/G4 antibodies in laboratory animal workers, similar to that observed in patients treated with high dose immunotherapy who become clinically tolerant, suggesting a potential explanation for the attenuation of risk at highest allergen exposures.
接触啮齿动物过敏原与实验动物过敏之间的关系较为复杂；在过敏原暴露水平最高时，致敏作用和症状会减弱，这与大鼠特异性免疫球蛋白（Ig）G和IgG4抗体水平升高有关。我们着手研究在我们的实验动物工作者队列中，之前在高过敏原暴露情况下观察到的大鼠特异性IgG和IgG4抗体水平升高是否通过阻断IgE-过敏原复合物与B细胞上CD23受体的结合发挥功能作用。
对英国六家制药公司的实验动物工作者（n = 776）进行横断面调查。在703名（97.9%）符合条件的员工中测量了IgE-过敏原复合物与B细胞的结合情况；根据工作岗位或每日接触大鼠的数量对他们的暴露情况进行分类。
我们观察到，随着大鼠特异性IgG和IgG4抗体四分位数的增加，IgE-过敏原复合物与B细胞的结合显著减少（p < 0.001）。高过敏原暴露的工作者中，IgE-过敏原复合物与B细胞的结合较低，在暴露水平最高但无工作相关胸部症状的亚组中更是如此（p = 0.033）。
这些发现证明了大鼠特异性IgG/G4抗体在实验动物工作者中发挥的功能作用，类似于在接受高剂量免疫治疗并产生临床耐受性的患者中观察到的情况，这为在最高过敏原暴露水平下风险降低提供了一种潜在解释。
