Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, SE-171 77 Stockholm, Sweden.
Int J Mol Sci. 2022 Jun 23;23(13):6984. doi: 10.3390/ijms23136984.
Cat allergy is a major trigger factor for respiratory reactions (asthma and rhinitis) in patients with immunoglobulin E (IgE) sensitization. In this study, we used a comprehensive panel of purified cat allergen molecules (rFel d 1, nFel d 2, rFel d 3, rFel d 4, rFel d 7, and rFel d 8) that were obtained by recombinant expression in or by purification as natural proteins to study possible associations with different phenotypes of cat allergy (i.e., rhinitis, conjunctivitis, asthma, and dermatitis) by analyzing molecular IgE recognition profiles in a representative cohort of clinically well-characterized adult cat allergic subjects ( = 84). IgE levels specific to each of the allergen molecules and to natural cat allergen extract were quantified by ImmunoCAP measurements. Cumulative IgE levels specific to the cat allergen molecules correlated significantly with IgE levels specific to the cat allergen extract, indicating that the panel of allergen molecules resembled IgE epitopes of the natural allergen source. rFel d 1 represented the major cat allergen, which was recognized by 97.2% of cat allergic patients; however, rFel d 3, rFel d 4, and rFel d 7 each showed IgE reactivity in more than 50% of cat allergic patients, indicating the importance of additional allergens in cat allergy. Patients with cat-related skin symptoms showed a trend toward higher IgE levels and/or frequencies of sensitization to each of the tested allergen molecules compared with patients suffering only from rhinitis or asthma, while there were no such differences between patients with rhinitis and asthma. The IgE levels specific to allergen molecules, the IgE levels specific to cat allergen extract, and the IgE levels specific to rFel d 1 were significantly higher in patients with four different symptoms compared with patients with 1-2 symptoms. This difference was more pronounced for the sum of IgE levels specific to the allergen molecules and to cat extract than for IgE levels specific for rFel d 1 alone. Our study indicates that, in addition to rFel d 1, rFel d 3, rFel d 4, and rFel d 7 must be considered as important cat allergens. Furthermore, the cumulative sum of IgE levels specific to cat allergen molecules seems to be a biomarker for identifying patients with complex phenotypes of cat allergy. These findings are important for the diagnosis of IgE sensitization to cats and for the design of allergen-specific immunotherapies for the treatment and prevention of cat allergy.
猫过敏是 IgE 敏感患者发生呼吸道反应(哮喘和鼻炎)的主要触发因素。在这项研究中,我们使用了通过重组表达或天然蛋白纯化获得的综合猫过敏原分子(rFel d 1、nFel d 2、rFel d 3、rFel d 4、rFel d 7 和 rFel d 8)面板来研究不同表型的猫过敏(即鼻炎、结膜炎、哮喘和皮炎)与过敏原分子之间可能存在的关联,方法是通过分析代表性的临床特征明确的成年猫过敏患者队列(=84)中的分子 IgE 识别图谱。通过 ImmunoCAP 测量来定量鉴定每个过敏原分子和天然猫过敏原提取物的特异性 IgE 水平。过敏原分子特异性的累积 IgE 水平与天然过敏原提取物特异性 IgE 水平显著相关,表明该面板过敏原分子类似于天然过敏原来源的 IgE 表位。rFel d 1 是主要的猫过敏原,97.2%的猫过敏患者对其有反应;然而,rFel d 3、rFel d 4 和 rFel d 7 各自在超过 50%的猫过敏患者中显示出 IgE 反应性,表明在猫过敏中存在其他过敏原的重要性。与仅患有鼻炎或哮喘的患者相比,患有与猫相关的皮肤症状的患者对每种测试过敏原分子的 IgE 水平和/或致敏频率呈上升趋势,而患有鼻炎和哮喘的患者之间则没有差异。与 1-2 种症状的患者相比,具有四种不同症状的患者的过敏原分子特异性 IgE 水平、猫过敏原提取物特异性 IgE 水平和 rFel d 1 特异性 IgE 水平显著更高。与 rFel d 1 相比,过敏原分子和猫提取物特异性 IgE 水平总和的这种差异更为明显。我们的研究表明,除了 rFel d 1 之外,rFel d 3、rFel d 4 和 rFel d 7 也必须被认为是重要的猫过敏原。此外,猫过敏原分子特异性 IgE 水平的累积总和似乎是识别具有复杂猫过敏表型患者的生物标志物。这些发现对于 IgE 对猫过敏的诊断以及设计用于治疗和预防猫过敏的过敏原特异性免疫疗法都很重要。