兽研1. 引言
猫和狗是现代生活环境中重要的室内过敏原蛋白来源[1]。它们的存在增加了暴露机会，但暴露本身并不等同于免疫致敏，致敏也不一定会导致有症状的过敏性疾病。与动物过敏原接触的临床相关性取决于暴露量和暴露时间、个体易感性，以及是否存在过敏原特异性IgE并伴有相符的临床病史[2,3,4]。城市化、室内生活方式以及人与动物接触模式的变化可能改变暴露机会，但这些因素不应被解释为过敏患病率增加的直接原因[1]。
猫和狗过敏原来源于多种生物材料，包括唾液、皮肤相关分泌物和皮屑、尿液、血清以及被分泌蛋白污染的毛发[2,3,4]。从分子角度看，Fel d 1是一种分泌球蛋白，是猫的主要过敏原，而狗过敏在分子层面更为异质，通常涉及载脂蛋白如Can f 1以及其他成分[2,5]。过敏原分子应与携带它们的环境颗粒相区分：Fel d 1和Can f 1等蛋白可附着于皮屑碎片、灰尘和跨越广泛粒径范围的气溶胶颗粒上。因此，呼吸道中的沉积取决于载体颗粒的空气动力学特性和吸入条件，而非固定的“过敏原颗粒大小”[3,4]。
在许多人群中，饲养宠物和密切的人与动物接触很常见，猫和狗过敏原经常在家庭、学校、工作场所和公共环境中被检测到，包括没有常住动物的场所[6,7]。这些观察表明暴露广泛存在，但本身并不能确定过敏性疾病因果性增加。致敏频率因人群、年龄、地理、宿主特应性和暴露模式而异；因此，环境过敏原水平和宠物饲养应被解释为依赖背景的贡献因素，而非致敏的普遍决定因素[2,3,4]。
在易感个体中，临床相关的猫或狗过敏最常由过敏原特异性IgE和I型超敏反应介导，表现为过敏性鼻炎、哮喘和结膜炎，部分患者出现特应性皮炎[2,3]。从暴露到疾病的途径并非确定性的。宿主易感性、遗传倾向、暴露年龄和时间、环境和微生物背景，以及过敏原暴露的强度和模式均可影响暴露后是否发生致敏或临床明显的过敏性疾病[2]。在解释环境测量和分子诊断结果时，这一区分至关重要。
近期综述分别强调了狗和猫过敏的诊断挑战[4]、组分解析诊断[8]、广泛的过敏原来源和发病机制[1]，以及接触家养和非家养动物的有利和不利后果[9]。本综述通过明确整合通常分别讨论的四个层面来扩展这些视角：(i) WHO/IUIS定义的过敏原分子，(ii) 遇到这些分子的环境载体和暴露条件，(iii) 从暴露到致敏和临床疾病的免疫转变，以及(iv) 分子诊断与临床表型和管理相关的解释。在整个综述中，暴露、IgE致敏和临床相关过敏被视为不同的概念，分子同源性区别于已证实的IgE交叉反应性和临床相关交叉过敏。连接过敏原来源、环境载体、暴露途径、IgE致敏和临床相关过敏的整合途径总结于图1。
2. 方法
本文以叙述性综述的形式撰写。通过PubMed/MEDLINE检索以及与人类对猫和狗过敏相关的文献，并筛选相关综述和所选文章的参考文献列表，检索的出版物时间范围为数据库建库至2026年7月。检索概念结合了与猫、狗、伴侣动物、Fel d、Can f、过敏原暴露、致敏、分子过敏学、组分解析诊断、交叉反应性、哮喘、鼻炎、免疫治疗、环境控制和过敏原中和相关的术语。纳入考虑的是英文、经同行评审的人体研究、共识文件、系统或叙述性综述，以及与解释人类对猫或狗过敏直接相关的机制研究。原始研究优先用于支持暴露、致敏、诊断发现和临床效应的定量估计，而综述和共识文件主要用于证据综合和既定术语。研究的选择依据其与预设范围和综述问题的相关性，而非通过正式的系统综述或荟萃分析方案。批判性评价重点关注研究人群、暴露或采样基质、过敏原检测方法、所评估的分子组分、临床结局的定义、方法学局限性，以及所报告的观察结果涉及的是环境暴露、免疫致敏还是临床相关过敏。由于本文为叙述性综述，未计算合并效应估计值。
3. 过敏原的来源与特征
3.1. 过敏原的来源与分布
来自猫和狗的致敏蛋白从唾液、皮肤相关分泌物和皮屑、尿液、血清及其他组织或分泌物中释放，随后可能污染毛发和室内储库[9,10,11]。梳理行为可将唾液蛋白分布至毛发和皮肤上，之后含过敏原的生物物质可能干燥、碎裂并融入灰尘或空气传播颗粒中[4]。因此，暴露量和暴露途径取决于动物源性分泌模式和环境载体的物理行为。
过敏原分子为蛋白质或糖蛋白，不应被赋予单一的空气动力学直径。在室内环境中，它们与异质性载体相关，包括皮屑碎片、灰尘颗粒、纤维和气溶胶液滴。沉积在鼻腔、传导气道或更远端呼吸道中的概率取决于载体颗粒的空气动力学特性、呼吸模式及其他沉积机制；因此，不应假定含过敏原颗粒均匀到达肺泡区域[3,4]。
3.2. WHO/IUIS认可的猫和狗过敏原
WHO/IUIS过敏原命名数据库认可家猫的Fel d 1-Fel d 8和家狗的Can f 1-Can f 8。因此，表1列出了所有目前认可的组分，而不仅仅是选定诊断平台上可用的组分。所报告的致敏频率取决于队列和检测方法；在稳健的组分特异性估计尚未建立或该组分在临床检测中不常规可用的情况下，会明确说明。“主要过敏原”仅在适当定义的过敏人群中IgE识别高患病率支持时使用，且属于某一蛋白家族不被视为临床交叉反应的证据。
3.3. 猫（Felis Domesticus）
在猫过敏原中，Fel d 1是主要过敏原，也是猫过敏患者IgE反应的主要靶标[25]。Fel d 1是属于分泌球蛋白家族的蛋白质，主要在皮脂腺、唾液腺和肛腺中产生，并通过毛发和皮肤释放到环境中[4]。该蛋白在室内环境中高度持久，即使在极低浓度下也可诱导过敏反应[26,27]。
Fel d 2属于血清白蛋白家族，存在于血液、唾液和皮肤中。由于该蛋白与其他动物物种的白蛋白具有高度结构相似性，它是交叉反应的主要原因[3]。例如，“猪肉-猫综合征”，即猫过敏患者对猪肉产生反应，可由Fel d 2与猪白蛋白之间的交叉反应解释[4]。
Fel d 4和Fel d 7属于脂质运载蛋白家族，来源于体液，其特征是易于分散到空气中。脂质运载蛋白在疏水性分子运输中发挥作用，并表现出高度结构保守性，这增加了跨物种交叉反应的可能性[3,27]。
3.4. 狗（Canis Familiaris）
狗过敏原比猫过敏原表现出更大的多样性，已鉴定出多种主要过敏原。代表性的主要过敏原包括Can f 1、Can f 2、Can f 4和Can f 6，它们均属于脂质运载蛋白家族[2,3,4]。这些蛋白质主要来源于唾液组织，并表现出IgE结合活性[5]。
Can f 5 在犬过敏原中具有独特的特征，因为它是一种在前列腺中产生的激肽释放酶家族酶。该过敏原仅在雄性犬体内产生，并通过尿液释放到环境中[3]。Can f 5 在结构上与人前列腺特异性抗原相似，这为 IgE 交叉反应提供了潜在的分子基础[3]。Can f 3 属于血清白蛋白家族，与其他哺乳动物的白蛋白具有高度同源性，这可能为跨物种的 IgE 交叉反应提供分子基础；然而，仅凭分子同源性并不能确立具有临床相关性的交叉反应[2,3,4]。
这些分子特征对过敏的诊断和治疗具有重要意义。传统的基于提取物的诊断检测在区分交叉反应方面能力有限，而组分解析诊断（CRD）可为评估分子致敏模式和潜在交叉反应提供额外信息[2,3,4]。
4. 过敏的免疫学机制
4.1. 过敏致敏过程
对犬和猫来源过敏原的免疫反应主要通过 IgE 介导的 I 型超敏反应介导，该反应经过一系列复杂的免疫事件[28,29]。当过敏原通过呼吸道进入机体时，首先与支气管黏膜和上皮细胞相互作用。在此过程中，上皮细胞分泌警报素细胞因子，如胸腺基质淋巴细胞生成素、IL-25 和 IL-33，从而启动免疫反应[30]。随后，过敏原被抗原呈递细胞（包括树突状细胞）捕获和处理，并通过 MHC II 类分子呈递给初始 CD4+ T 细胞[28]。特定的细胞因子环境，特别是 IL-4 的存在，促进 T 细胞向 Th2 表型分化，这是过敏反应中的关键步骤[31]。
活化的 Th2 细胞产生具有不同功能的细胞因子。IL-4 和 IL-13 是促进 B 细胞类别转换向 IgE 的中心信号，而 IL-5 主要支持嗜酸性粒细胞的分化、募集和存活，而非直接诱导 IgE 类别转换[28]。产生的过敏原特异性 IgE 通过血液循环，并与表达于肥大细胞和嗜碱性粒细胞表面的 FcεRI（高亲和力 IgE 受体）结合[31,32]。再次暴露于相同过敏原时，过敏原交联与 IgE 结合的 FcεRI 受体，从而诱导肥大细胞脱颗粒[28]。在此过程中，组胺、白三烯和前列腺素等炎症介质被释放，导致血管扩张、黏液分泌增加和支气管收缩，临床表现为过敏性鼻炎、哮喘和结膜炎[29]。
迟发和慢性反应可能涉及嗜酸性粒细胞、Th2 细胞、ILC2 细胞和组织重塑通路[30]。Fel d 1 是主要的猫过敏原，而犬过敏在分子上更具异质性，可能涉及多种组分，包括 Can f 1、Can f 2、Can f 3、Can f 4、Can f 5 和 Can f 6[2]。因此，对猫和犬过敏原的免疫反应应在单个过敏原组分水平上进行解读，而不是将所有犬过敏原组分赋予统一的免疫学特性。从上皮对过敏原的识别到 Th2 极化、IgE 产生、肥大细胞活化和临床过敏反应的免疫学序列见图 2。
4.2. IgG4 的调节作用及临床解读
尽管 IgE 抗体在过敏性免疫反应中发挥核心作用，但 IgG4 抗体执行免疫调节功能[33]。IgG4 通常在反复和长期抗原暴露的条件下产生，并与免疫耐受密切相关[28,32]。在急性或初次过敏原暴露期间，Th2 反应占主导地位，增加 IgE 产生并促进过敏反应。然而，在持续和低剂量反复暴露下，免疫系统逐渐产生调节性反应，在此期间，免疫抑制性细胞因子（如 IL-10 和 TGF-β）增加并促进 IgG4 产生[28,32]。
过敏原特异性 IgG4 可在反复过敏原暴露期间和成功的过敏原免疫治疗期间升高，并可通过与 IgE 依赖性过敏原识别竞争而发挥阻断抗体的作用[28,33]。然而，IgG4 是更广泛调节性反应的一个要素，该反应包括 Treg 细胞、IL-10、TGF-β、效应细胞活化变化以及抗体质量改变。因此，过敏原特异性 IgG4 的升高最好被视为一种机制性或药效学标志物，而非常规接受的个体临床 AIT 疗效的独立替代指标。临床反应必须使用症状、药物使用、适当情况下的激发试验结果和疾病控制来评估[32]。
4.3. 卫生假说与基于微生物组的免疫调节
解释过敏性疾病患病率不断增加的一个理论是卫生假说，该假说提出生命早期的微生物暴露在免疫系统发育中发挥重要作用[34,35]。根据该假说，儿童期接触多样化的微生物和环境抗原可维持 Th1 和 Th2 免疫反应之间的平衡，从而降低过敏性疾病的发生率[35]。
伴侣动物可能影响室内环境的微生物特征，因为宠物是构成室内微生物群落的来源之一[36]。室内微生物暴露与过敏性疾病和炎症性疾病相关，尽管这些关联的方向和强度在不同研究中存在差异[36]。此类微生物暴露可能通过多种免疫学机制影响过敏性疾病，包括调节Th2相关应答和调节性免疫通路[35]。然而，这些效应并非一致具有保护性，微生物暴露与过敏性疾病之间的关系似乎取决于具体背景[35,36]。
室内微生物群落的多样性和组成受多种环境和人为因素影响，包括建筑特征、通风、居住情况以及居住者的生活方式[36]。同样，伴侣动物暴露与过敏性疾病之间的关系也并不一致。在一些研究中，早期接触犬与致敏可能性降低相关，而关于猫暴露的研究结果则不一致，且暴露的时间和水平可能影响这些结局[4]。因此，应在更广泛的环境和免疫学背景中理解伴侣动物暴露，而不应将其视为一致具有保护性或一致有害。
5. 暴露与传播
5.1. 直接暴露
暴露可能通过与动物的直接身体接触发生，也可能通过共享室内环境中的含过敏原物质间接发生。这些暴露情形不会导致等效的暴露水平，因为实际暴露随暴露强度和模式以及室内环境特征而变化[4,37]。
当伴侣动物在室内饲养时，过敏原可在纺织品表面（如地毯、床上用品和沙发）积聚，这些表面可能起到过敏原储库的作用[26]。这些积聚的过敏原可能因环境扰动而悬浮到空气中，导致间歇性或反复吸入暴露，而非恒定的空气浓度。这种反复暴露可能导致已致敏个体出现症状，而致敏的发生取决于多种宿主相关和暴露相关因素[3,4]。此外，频繁接触动物的职业群体，包括兽医和动物护理工作者，可能经历大量过敏原暴露，并增加工作相关过敏症状的风险[10]。
5.2. 间接暴露
间接暴露是指即使在不直接饲养或接触伴侣动物的环境中也会遇到过敏原的暴露途径。宠物来源的过敏原可通过人类衣物、鞋子、头发和包袋等多种载体轻易传播，这种被动转移导致室内环境的广泛污染[10,38]。在没有猫的学校教室中发现的猫过敏原浓度高于无猫家庭，但低于有猫家庭[7]。例如，Fel d 1和Can f 1已在学校灰尘中检出，包括猫或犬无法直接进入的环境，表明猫和犬来源过敏原具有间接转移的潜力[39]。
宠物来源的过敏原已在其他公共设施中检出，如公共交通系统、医院、酒店和办公室，可能导致即使未直接接触伴侣动物的个体也发生持续性低水平暴露[3]。这种间接暴露可能尤其在对敏感个体中触发症状，并且是使暴露避免策略复杂化的主要因素。此外，间接暴露还可能通过与空气细颗粒物结合而促进长距离传输[10]。这表明过敏原并非局限于特定空间，而可能存在于不同环境中。
5.3. 暴露水平
环境研究报告了沉降式房屋灰尘中Fel d 1和Can f 1浓度与致敏和哮喘的关系，但所报告的暴露水平不应被解释为普遍适用的生物学阈值。在一项针对新墨西哥州洛斯阿拉莫斯12–14岁学童的研究中，使用双位点免疫分析法测定了沉降式房屋灰尘中的Fel d 1和Can f 1。Fel d 1浓度≥8 μg/g灰尘和Can f 1浓度≥10 μg/g灰尘被用于界定相对较高的家庭暴露；然而，当前家庭过敏原浓度与个体儿童的致敏或症状并无明确关联[40]。因此，这些数值应被解释为研究特定的暴露水平，而非普遍适用的临床阈值。
暴露–反应关系因研究人群、个体易感性、暴露环境、采样方法、分析方法和临床结局而异。灰尘中或表面上可检出过敏原的持续存在表明存在环境储库，但仅检出并不能确立具有临床相关性的暴露或症状性疾病[37]。
6. 交叉反应与多重致敏
6.1. 交叉反应
免疫学交叉反应是指不同物种的蛋白质被IgE抗体相似地识别，这种现象在物种间经常发生[3,25]。此类交叉反应是使过敏性疾病诊断和治疗复杂化的主要因素[41,42]。
交叉反应需要存在共同的IgE识别表位，应将其与仅仅属于同一蛋白质家族区分开来。结构同源性可为交叉反应提供分子基础，但仅有同源性并不能证明IgE交叉反应，而IgE交叉反应也不一定转化为临床相关的交叉过敏。这些区别对于脂质运载蛋白和血清白蛋白尤为重要[3,42]。
一个代表性例子是猫过敏原Fel d 2（血清白蛋白）与猪Sus s 1（血清白蛋白）之间的交叉反应，该交叉反应是猪肉-猫综合征的基础。IgE抑制研究表明，对猫血清白蛋白致敏可能是首要事件，随后出现对猪血清白蛋白的交叉反应以及食用猪肉后的过敏反应[13]。
几种哺乳动物脂质运载蛋白显示出序列和结构相似性。例如，分子研究已证实Fel d 4与Can f 6之间的IgE交叉反应[22,43]。然而在临床解读中，对两种组分均呈阳性IgE结果可能反映真正的共同致敏、交叉反应性IgE或两者兼有。因此，不应仅因原始致敏来源或临床相关性尚不确定就将IgE阳性解读为假阳性结果。
另一个例子是狗过敏原Can f 5与人前列腺特异性抗原（PSA）之间的IgE交叉反应，两者均为激肽释放酶蛋白家族成员。该交叉反应的临床相关性已在一例人类精液血浆过敏中得到证实[44]。这一发现提示宠物来源的过敏原也可与同源人类蛋白质发生交叉反应。此类多样化的交叉反应使真正致病过敏原的鉴定变得复杂，而传统的基于提取物的诊断方法在区分这些差异方面能力有限[2,4]。因此，CRD有助于区分交叉反应与真正致敏[3]。
图3区分了分子过敏学中的三个证据水平：蛋白质家族或序列同源性、实验证实的IgE交叉反应，以及由暴露-反应一致性支持的临床相关交叉过敏。该框架可防止将结构相似性解读为临床交叉反应的证据。
6.2. 多致敏
多致敏是指对多种过敏原来源或分子组分存在IgE致敏，可能反映共同致敏、交叉反应性IgE或两者兼有[3]。一些队列研究将更广泛的分子致敏谱与哮喘及更严重的疾病相关联；然而，仅凭致敏谱并不能确定临床严重程度或相关性[3,8]。因此，解读时应综合考虑IgE致敏的强度和分子模式，以及暴露史、症状出现时间、合并症和临床表型[3]。
CRD可通过识别IgE所识别的特定分子组分来细化对多致敏患者的特征描述。它可能有助于区分原发致敏与潜在交叉反应，但其本身并不能确定哪种过敏原引起症状。因此，结果必须与暴露史和症状出现时间相结合，当临床相关性仍不确定时，还需结合激发试验或其他功能学检测[3,8]。
多致敏可能源于多种过敏原暴露、交叉反应和免疫应答之间复杂的相互作用。因此，动物过敏患者的评估和治疗需要采用既考虑致敏的存在、又考虑该致敏的潜在机制和临床意义的方法。
7. 临床表现
7.1. 呼吸系统疾病
临床相关的猫和狗过敏在具有相容暴露史的致敏个体中最常表现为过敏性鼻炎、结膜炎和/或哮喘[29]。这些反应发生在含过敏原的载体颗粒或污染物质到达上呼吸道或下呼吸道或眼黏膜之后；不应将其描述为单一固定“过敏原颗粒大小”的结果[3,4]。
过敏性鼻炎是最常见的临床表现，其特征为打喷嚏、流涕、鼻塞和鼻痒等症状。这些症状由IgE介导的炎症反应和鼻黏膜内肥大细胞脱颗粒引起，反复暴露后可能进展为慢性炎症性疾病[45]。特别是主要猫过敏原Fel d 1易于在空气中传播，相当一部分附着于可长时间悬浮的小颗粒上[26]。
支气管哮喘是一种更为严重的呼吸系统疾病，其特征为气道炎症、气道狭窄、黏液分泌过多及气道高反应性[31]。在致敏患者中，反复暴露可诱导气道上皮损伤和免疫细胞浸润，进而可能导致慢性炎症和结构重塑[30]。在遗传易感个体中，对宠物源性变应原的致敏与哮喘发生风险增加相关，而生命早期接触伴侣动物在某些条件下可能与后续过敏性致敏风险降低相关[4,46]。
接触猫变应原可诱导早期和晚期哮喘反应。在患有哮喘的猫过敏患者中，变应原激发后的晚期哮喘反应可在暴露后长达24小时出现[47]。
犬变应原致敏与儿童哮喘严重程度相关。特别是，对Can f 2的致敏以及对动物源性脂质运载蛋白的更广泛多重致敏，在重症哮喘儿童中的报告频率高于控制良好的哮喘儿童[48,49]。
7.2. 皮肤及全身性过敏反应
犬和猫源性变应原可诱导皮肤及全身性反应。代表性的皮肤表现为特应性皮炎，由皮肤屏障功能异常和免疫反应异常共同导致[50]。特应性皮炎以瘙痒、红斑、皮肤干燥和苔藓化为特征，在易感个体中可由吸入性变应原触发[50]。接触Fel d 1等变应原可触发免疫反应[4]。过敏性结膜炎也是一种常见表现，以眼部瘙痒、结膜充血和泪液分泌增加为特征。该病症由IgE介导的反应及结膜组织内肥大细胞活化引起[29]。
与呼吸道和眼部表现相比，由猫或犬变应原引起的全身性反应似乎不常见。过敏反应是猫或犬过敏的罕见临床表现。发生过敏反应时，可能危及生命，需要立即治疗[51]。此外，部分患者可通过宠物源性变应原与食物变应原之间具有临床相关性的交叉反应而发生全身性反应[13,42]。
7.3. 影响疾病严重程度和临床异质性的因素
猫和犬过敏的临床表现患者间存在显著异质性，反映了多种宿主相关、暴露相关和变应原相关因素的影响[3]。对单个变应原组分的致敏可能与不同的临床表型相关；例如，对Can f 5的单一致敏与对公犬而非母犬的选择性临床反应性相关[52]。然而，对单个变应原组分致敏或多重致敏与临床严重程度之间的关联应以概率性而非确定性方式解读。既不应将对单一组分（如Fel d 1或Can f 5）的致敏，也不应仅将多重致敏视为症状严重程度的直接衡量指标[3]。
遗传易感性、变应原暴露以及空气污染等环境因素可影响临床表现和疾病严重程度[30]。特别是，婴儿期环境暴露可能影响后续过敏性致敏及儿童期后期过敏性疾病的风险[46]。为实现精准管理，分子致敏谱应与患者临床表型、炎症反应模式和暴露史结合解读，而非孤立使用[3]。
8. 诊断
8.1. 传统诊断方法
人类猫或犬过敏的诊断需要相容的临床病史、相关暴露和IgE致敏证据三者一致[53]。皮肤点刺试验和血清变应原特异性IgE检测仍是记录致敏状态的一线工具，但阳性检测本身并不能确定动物暴露是症状的原因。表2总结了传统方法和分子方法，并强调其互补作用，而非将CRD列为本质上更具临床特异性。
血清特异性IgE检测定量测定患者血液样本中针对特定变应原的IgE抗体，当SPT难以实施时（如皮肤病患者或服用抗组胺药者）可作为替代方法[54]。ImmunoCAP等标准化方法提供高重现性和客观性，并能够对各种变应原进行定量比较[54]。
尽管这些传统的提取物诊断方法广泛使用，但存在若干局限性。第一，变应原提取物由蛋白质的复杂混合物组成，因此无法区分单个变应原组分，难以区分交叉反应与真正致敏[3]。例如，对血清白蛋白等常见蛋白的IgE反应可能表现为不同动物物种间的交叉反应，从而掩盖真正的致敏来源[42]。第二，变应原提取物的组成可能因生产工艺和原材料而存在显著差异，导致标准化方面的局限性[2,3,4]。
第三，SPT和特异性IgE检测结果并不总是与临床症状直接对应。换言之，可能存在致敏状态而无临床过敏表现[29]。这表明在诊断过程中必须始终将暴露史和症状模式结合考虑。此外，对于宠物来源的过敏原，许多患者表现出多重致敏模式，即同时对多种动物或过敏原产生反应，使得仅依靠提取物检测方法难以确定确切的致病过敏原[2,3,4]。
8.2. 分子诊断（CRD）
组分解析诊断（CRD）测定针对单个过敏原分子的IgE，可在全提取物检测的基础上进一步细化致敏谱[2,8]。它特别适用于鉴定物种相关标志性组分以及识别与血清白蛋白或脂质运载蛋白交叉反应相容的模式。然而，CRD不能独立确立临床因果关系，其结果应结合患者临床病史和相关暴露信息进行解读[42]。
已有报道描述了单个过敏原组分、多重致敏模式、哮喘与疾病严重程度之间的关联；然而，过敏原分子作为疾病严重程度预测因子的作用尚需进一步研究[8]。因此，CRD可能有助于患者特征描述和诊断明确化，但不应作为疾病严重程度的独立预测指标或治疗决策的决定因素。
当提取物检测、组分结果、暴露史和症状之间存在不一致时，可在专科实践中考虑进一步评估。控制性鼻过敏原激发试验有助于在特定患者中确立致敏的临床相关性，而嗜碱性粒细胞活化试验可在常规诊断方法无法得出结论或结果相互矛盾时提供额外的功能性诊断信息[55,56]。这些检测并非常规必需，但它们说明了证明致敏与确立临床相关过敏之间的区别。
CRD受限于各平台的组分库、检测特异性性能、成本、可及性以及解读复杂图谱所需的专业知识。因此，CRD应补充而非替代临床病史、体格检查和常规过敏检测。其对个体化管理的贡献主要在于细化分子致敏谱和患者分类，而治疗决策仍应基于整体临床情况，而非仅依据CRD结果[8]。
9. 治疗与管理
9.1. 过敏原回避
管理首先从可行时减少临床相关暴露开始，但过敏原回避不应被描述为普遍确定或充分的手段。实际目标是减少对免疫学和临床均相关过敏原的暴露，同时认识到移除宠物带来的社会和情感后果。由于动物移除后过敏原储库仍可能持续存在，环境暴露可能继续，仍可能需要额外的环境措施[26]。决策应根据疾病严重程度、暴露-反应一致性以及患者偏好进行个体化制定。宠物过敏的主要管理策略及其优势和局限性总结于表3。
9.2. 环境控制
环境控制可降低空气传播或储库过敏原的实测浓度，但过敏原浓度的降低不一定产生等效的临床改善[37,57]。HEPA过滤、储库减少、清洁和卧室隔离可作为多模式策略的组成部分加以考虑。其临床有效性随依从性、基线暴露、房间特征和主要暴露途径而变化；因此，环境过敏原减少和以患者为中心的临床获益应作为不同的结局分别报告。
定期清洁可能有助于减少环境中过敏原的积累。特别是床上用品、窗帘和地毯是易于积累过敏原的表面[26]。然而，传统吸尘器可能将过敏原重新悬浮至空气中，因此推荐使用配备HEPA过滤器的工具。
行为措施如限制动物进入卧室、接触后洗手以及选择性清洁或梳理操作可能有助于降低暴露，但通常只能提供部分而非完全的减少。建议应针对个体量身定制，且不应暗示降低实测环境过敏原浓度即可保证症状控制。
9.3. 标准药物治疗
标准药物治疗仍然是症状性猫犬过敏治疗的核心，应根据受累器官系统和疾病严重程度进行选择。可选方案包括用于过敏性鼻炎和结膜症状的第二代H1抗组胺药，以及用于持续性过敏性鼻炎的鼻内糖皮质激素[58]。对于哮喘患者，治疗应遵循现行哮喘指南，并包括含吸入性糖皮质激素（ICS）的方案；不推荐单独按需使用短效β2受体激动剂（SABA）[59]。这些药物针对患者的炎症性和症状性疾病进行治疗，但不能消除致敏状态或环境过敏原暴露；因此，药物治疗应与暴露管理相结合，并在特定患者中联合过敏原免疫治疗或生物制剂治疗。
9.4. 过敏原免疫治疗
过敏原免疫治疗（AIT）旨在通过反复给予临床相关过敏原制剂诱导持久免疫耐受[28,32]。其在猫犬过敏中的应用需要仔细筛选患者、确认动物过敏原具有临床相关性，并关注提取物的组成和标准化。
AIT与T细胞调节、效应细胞反应性、过敏原特异性IgE以及封闭抗体（如IgG4）的变化相关。IgG4升高可伴随AIT成功出现，但不应将其作为临床疗效的个体替代指标。临床获益必须通过经过验证的症状、用药和疾病控制结局进行评估。
猫和犬过敏原免疫治疗的证据应分别考虑。使用标准化猫提取物的对照研究已证明在特定猫过敏患者中具有获益，包括减少猫暴露期间的症状和降低猫特异性支气管反应性[60,61]。犬AIT的证据基础说服力较弱，因为犬提取物在分子层面具有异质性、标准化具有挑战性，且高质量随机对照试验数量有限[4,53]。因此，疗效不应从猫AIT推广至犬AIT，也不应从更成熟的适应证（如屋尘螨或花粉过敏）推广至猫犬过敏。
尽管AIT具有获益，但其需要长期治疗，通常为3~5年，并受成本和患者依从性限制[29,62]。部分患者可能在治疗期间出现局部或全身不良反应，也有罕见过敏性休克病例的报道[28]。除传统皮下免疫治疗外，舌下免疫治疗等多种方法已被开发，旨在提高患者便利性和安全性的研究仍在继续。
9.5. 新型治疗策略
针对来源的过敏原中和策略受到关注，因为其旨在减少暴露而不移除动物。含蛋源抗Fel d 1 IgY的饮食已被证明可减少猫唾液或毛发上具有免疫活性的Fel d 1[63]。然而，活性Fel d 1减少属于过敏原暴露结局，不应等同于在过敏人群中已证实的临床获益；证明患者症状获得有临床意义改善的证据仍然有限。
一种临床上有区别的被动免疫治疗策略使用两种全人源Fel d 1中和IgG4单克隆抗体REGN1908和REGN1909，直接给予过敏患者，而非在动物来源减少过敏原产生。在一项随机、双盲、安慰剂对照试验中，单剂REGN1908–1909减少了受控猫过敏原激发后的鼻部症状，并抑制了IgE介导和2型炎症反应[64]。随后一项在伴轻度哮喘的猫过敏患者中开展的随机环境暴露单元研究发现，单次600 mg剂量可显著减轻过敏原诱导的FEV1下降和早期哮喘反应，持续时间长达85天[65]。这些发现为在人类中被动中和Fel d 1提供了概念验证，但这种针对患者的单克隆抗体策略在机制和临床上均不同于针对来源的抗Fel d 1 IgY饮食。
重组或修饰Fel d 1分子及基于肽的方法正在作为提高免疫治疗特异性或耐受性的策略进行研究[66]。抗IgE治疗等生物制剂已确立用于特定临床适应证，包括特定重度过敏性哮喘患者，但不应将其作为猫或犬致敏的通用治疗方法[67]。
其他方法，包括基于肽的免疫治疗和过敏原中和策略，仍处于研究阶段[63,66]。其临床价值需要对照试验证明以患者为中心的结局，这有别于免疫学变化或过敏原减少的实验室证据。
动物过敏无法仅通过单一方法得到充分管理，可能需要整合过敏原回避、环境控制、免疫治疗和新兴治疗手段的多层面策略。将分子致敏谱与临床表现、暴露史和疾病严重程度相结合的个性化管理策略，可能有助于支持更个体化的临床决策。例如，CRD等分子诊断方法可细化分子致敏谱，当与暴露史和临床表型结合解读时，可为个体化临床决策提供补充信息[3]。
10. 结论
人类对猫和狗的过敏在临床上具有重要意义，但宠物饲养、城市化或室内生活的人群层面趋势不应被解读为过敏性疾病相应增加的直接证据。这些社会因素可改变暴露机会，而致敏和有症状的过敏源于过敏原剂量与暴露时机、分子致敏、宿主易感性、屏障与免疫反应以及疾病表型之间的相互作用。
猫和狗来源的致敏蛋白可在灰尘中持续存在并被运输至无常住动物的环境中，但环境检测并不一定表明对每个个体都具有临床相关暴露。同样，在某些队列中多重致敏可能与更复杂的表型相关，但仅凭IgE阳性反应的数量并不能决定疾病严重程度。临床解读需要将分子致敏谱与症状、暴露模式以及个体免疫和气道特征相联系。
分子过敏学改善了猫和狗致敏的特征描述，有助于区分物种相关标志物致敏与符合交叉反应的模式。因此，CRD是有价值的诊断支持工具，但它不能独立确定因果过敏原或决定治疗。在不确定性持续存在时，暴露-反应一致性以及在特定专科环境下进行的激发试验或功能检测可提供额外证据。
管理最好被构建为一种分层策略，将临床适当的药物治疗与可行的暴露减少相结合，并对选定患者采用过敏原免疫治疗或疾病特异性生物制剂治疗。猫AIT的证据比狗AIT更为成熟，而诸如抗Fel d 1 IgY等新兴源头控制方法应分别针对过敏原减少和以患者为中心的临床获益进行评估。未来研究应优先关注标准化分子暴露评估、组分谱与临床表型的前瞻性关联、高质量狗AIT试验，以及同时测量环境过敏原减少和有意义症状结局的干预研究。
因此，猫和狗过敏的精准方法与其说依赖于任何单一检测或暴露测量，不如说依赖于分子致敏、暴露-反应关系、炎症表型和以患者为中心结局的整合。
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1. Introduction
Cats and dogs are important sources of indoor allergenic proteins in modern living environments [1]. Their presence increases opportunities for exposure, but exposure itself is not equivalent to immunological sensitization, and sensitization does not necessarily result in symptomatic allergic disease. The clinical relevance of contact with animal allergens depends on the amount and timing of exposure, individual susceptibility, and the presence of allergen-specific IgE together with a compatible clinical history [2,3,4]. Urbanization, indoor lifestyles, and changes in patterns of human–animal contact may alter exposure opportunities, but these factors should not be interpreted as direct causes of increasing allergy prevalence [1].
Cat and dog allergens originate from several biological materials, including saliva, skin-associated secretions and dander, urine, serum, and fur contaminated with secreted proteins [2,3,4]. From a molecular perspective, Fel d 1, a secretoglobin, is the dominant cat allergen, whereas dog allergy is molecularly more heterogeneous and commonly involves lipocalins such as Can f 1 as well as other components [2,5]. Allergen molecules should be distinguished from the environmental particles that carry them: proteins such as Fel d 1 and Can f 1 can associate with dander fragments, dust, and aerosol particles spanning a broad size range. Consequently, deposition in the respiratory tract depends on the aerodynamic properties of the carrier particle and inhalation conditions rather than on a fixed “allergen particle size” [3,4].
Pet ownership and close human–animal contact are common in many populations, and cat and dog allergens are frequently detected in homes, schools, workplaces, and public environments, including locations without resident animals [6,7]. These observations demonstrate widespread exposure but do not by themselves establish a causal increase in allergic disease. Sensitization frequencies vary according to population, age, geography, host atopy, and exposure patterns; therefore, environmental allergen levels and pet ownership should be interpreted as context-dependent contributors rather than universal determinants of sensitization [2,3,4].
In susceptible individuals, clinically relevant cat or dog allergy is most often mediated by allergen-specific IgE and type I hypersensitivity, with manifestations that include allergic rhinitis, asthma, and conjunctivitis and, in some patients, atopic dermatitis [2,3]. The pathway from exposure to disease is not deterministic. Host susceptibility, genetic predisposition, age and timing of exposure, environmental and microbial context, and the intensity and pattern of allergen exposure can influence whether exposure is followed by sensitization or clinically apparent allergic disease [2]. This distinction is essential when interpreting environmental measurements and molecular diagnostic results.
Recent reviews have separately emphasized diagnostic challenges in dog and cat allergy [4], component-resolved diagnostics [8], broad allergen sources and pathogenesis [1], and the favorable and unfavorable consequences of exposure to domestic and non-domestic animals [9]. The present review extends these perspectives by explicitly integrating four levels that are often discussed separately: (i) WHO/IUIS-defined allergen molecules, (ii) the environmental carriers and exposure conditions through which these molecules are encountered, (iii) the immunological transition from exposure to sensitization and clinical disease, and (iv) the interpretation of molecular diagnostics in relation to clinical phenotype and management. Throughout the review, exposure, IgE sensitization, and clinically relevant allergy are treated as distinct concepts, and molecular homology is distinguished from demonstrated IgE cross-reactivity and from clinically relevant cross-allergy. The integrated pathway linking allergen sources, environmental carriers, exposure routes, IgE sensitization, and clinically relevant allergy is summarized in Figure 1.
2. Methods
This article was prepared as a narrative review. Literature relevant to human allergy to cats and dogs was identified through PubMed/MEDLINE and by screening the reference lists of relevant reviews and selected articles, with publications considered from database inception through July 2026. Search concepts combined terms related to cat, dog, companion animal, Fel d, Can f, allergen exposure, sensitization, molecular allergology, component-resolved diagnosis, cross-reactivity, asthma, rhinitis, immunotherapy, environmental control, and allergen neutralization. English-language, peer-reviewed human studies, consensus documents, systematic or narrative reviews, and mechanistic studies directly relevant to the interpretation of human allergy to cats or dogs were considered. Primary studies were preferentially used to support quantitative estimates of exposure, sensitization, diagnostic findings, and clinical effects, whereas reviews and consensus documents were used primarily for evidence synthesis and established terminology. Studies were selected according to their relevance to the predefined scope and review questions rather than through a formal systematic-review or meta-analytic protocol. Critical appraisal focused on the study population, exposure or sampling matrix, allergen assay, molecular component evaluated, definition of clinical outcomes, methodological limitations, and whether the reported observation concerned environmental exposure, immunological sensitization, or clinically relevant allergy. Because this was a narrative review, no pooled effect estimates were calculated.
3. Origin and Characteristics of Allergens
3.1. Origin and Distribution of Allergens
Allergenic proteins from cats and dogs are released from saliva, skin-associated secretions and dander, urine, serum, and other tissues or secretions, and may subsequently contaminate fur and indoor reservoirs [9,10,11]. Grooming can distribute salivary proteins over fur and skin, after which allergen-containing biological material may dry, fragment, and become incorporated into dust or airborne particles [4]. The amount and route of exposure therefore depend on both animal-derived secretion patterns and the physical behavior of the environmental carrier.
Allergen molecules are proteins or glycoproteins and should not be assigned a single aerodynamic diameter. In indoor environments, they are associated with heterogeneous carriers, including dander fragments, dust particles, fibers, and aerosol droplets. The probability of deposition in the nose, conducting airways, or more distal respiratory tract depends on the aerodynamic properties of the carrier particle, breathing pattern, and other deposition mechanisms; therefore, allergen-containing particles should not be assumed to uniformly reach the alveolar region [3,4].
3.2. WHO/IUIS-Recognized Cat and Dog Allergens
The WHO/IUIS Allergen Nomenclature database recognizes Fel d 1-Fel d 8 for domestic cat and Can f 1-Can f 8 for domestic dog. Table 1 therefore lists all currently recognized components rather than only components available on selected diagnostic platforms. Reported sensitization frequencies are cohort- and assay-dependent; where robust component-specific estimates are not established or the component is not routinely available in clinical assays, this is stated explicitly. “Major allergen” is used only when supported by a high prevalence of IgE recognition in an appropriately defined allergic population, and membership in a protein family is not treated as evidence of clinical cross-reactivity.
3.3. Cat (Felis Domesticus)
Among cat allergens, Fel d 1 is the major allergen and a principal target of IgE responses in patients with cat allergy [25]. Fel d 1 is a protein belonging to the secretoglobin family and is primarily produced in sebaceous, salivary, and anal glands, from which it is released into the environment through fur and skin [4]. This protein is highly persistent in indoor environments and can induce allergic reactions even at very low concentrations [26,27].
Fel d 2 belongs to the serum albumin family and is found in blood, saliva, and skin. As this protein shares high structural similarity with albumins from other animal species, it serves as a major cause of cross-reactivity [3]. For example, the “pork-cat syndrome,” in which patients with cat allergy react to pork, is explained by cross-reactivity between Fel d 2 and porcine albumin [4].
Fel d 4 and Fel d 7 belong to the lipocalin family, originate from body fluids, and are characterized by their ability to disperse readily into the air. Lipocalin proteins function in the transport of hydrophobic molecules and exhibit high structural conservation, raising the possibility of cross-reactivity across species [3,27].
3.4. Dog (Canis Familiaris)
Dog allergens exhibit greater diversity than cat allergens, with multiple major allergens identified. Representative major allergens include Can f 1, Can f 2, Can f 4, and Can f 6, all of which belong to the lipocalin protein family [2,3,4]. These proteins are primarily derived from salivary tissues and exhibit IgE-binding activity [5].
Can f 5 possesses unique characteristics among dog allergens, as it is a kallikrein-family enzyme produced in the prostate gland. This allergen is generated exclusively in male dogs and is released into the environment through urine [3]. Can f 5 exhibits structural similarity to human prostate-specific antigen, which provides a potential molecular basis for IgE cross-reactivity [3]. Can f 3 belongs to the serum albumin family and exhibits high homology with albumins from other mammals, which may provide a molecular basis for IgE cross-reactivity across species; however, molecular homology alone does not establish clinically relevant cross-reactivity [2,3,4].
These molecular characteristics have implications for allergy diagnosis and treatment. Conventional extract-based diagnostic tests are limited in their ability to distinguish cross-reactivity, whereas component-resolved diagnosis (CRD) can provide additional information for evaluating molecular sensitization patterns and potential cross-reactivity [2,3,4].
4. Immunological Mechanisms of Allergy
4.1. Process of Allergic Sensitization
Immunological responses to dog- and cat-derived allergens are primarily mediated through IgE-mediated type I hypersensitivity reactions, which proceed through a complex series of immunological events [28,29]. When allergens enter the body through the respiratory tract, they first interact with bronchial mucosa and epithelial cells. During this process, epithelial cells secrete alarmin cytokines, such as thymic stromal lymphopoietin, IL-25, and IL-33, thereby initiating immune responses [30]. Subsequently, allergens are captured and processed by antigen-presenting cells, including dendritic cells, and are presented to naïve CD4+ T cells through MHC class II molecules [28]. A specific cytokine environment, particularly the presence of IL-4, promotes the differentiation of T cells into the Th2 phenotype, which represents a critical step in allergic responses [31].
Activated Th2 cells produce cytokines with distinct functions. IL-4 and IL-13 are central signals promoting B-cell class switching toward IgE, whereas IL-5 primarily supports eosinophil differentiation, recruitment, and survival rather than directly inducing IgE class switching [28]. The generated allergen-specific IgE circulates through the bloodstream and binds to FcεRI (high-affinity IgE receptors) expressed on the surface of mast cells and basophils [31,32]. Upon re-exposure to the same allergen, the allergen cross-links FcεRI receptors bound to IgE, thereby inducing mast cell degranulation [28]. During this process, inflammatory mediators such as histamine, leukotrienes, and prostaglandins are released, resulting in vasodilation, increased mucus secretion, and bronchoconstriction, which manifest clinically as allergic rhinitis, asthma, and conjunctivitis [29].
Late and chronic responses may involve eosinophils, Th2 cells, ILC2 cells, and tissue-remodeling pathways [30]. Fel d 1 is the major cat allergen, whereas dog allergy is molecularly more heterogeneous and may involve multiple components, including Can f 1, Can f 2, Can f 3, Can f 4, Can f 5, and Can f 6 [2]. Accordingly, the immunological response to cat and dog allergens should be interpreted at the level of individual allergenic components rather than by attributing a uniform immunological property to all dog allergen components. The immunological sequence from epithelial allergen recognition to Th2 polarization, IgE production, mast-cell activation, and clinical allergic responses is illustrated in Figure 2.
4.2. Regulatory Role and Clinical Interpretation of IgG4
Although IgE antibodies play a central role in allergic immune responses, IgG4 antibodies perform immunoregulatory functions [33]. IgG4 is generally produced under conditions of repeated and long-term antigen exposure and is closely associated with immune tolerance [28,32]. During acute or initial allergen exposure, Th2 responses predominate, increasing IgE production and promoting allergic reactions. However, under persistent and low-dose repeated exposure, the immune system gradually develops regulatory responses, during which immunosuppressive cytokines, such as IL-10 and TGF-β, increase and promote IgG4 production [28,32].
Allergen-specific IgG4 can increase during repeated allergen exposure and during successful allergen immunotherapy and can function as a blocking antibody by competing with IgE-dependent allergen recognition [28,33]. However, IgG4 is one element of a broader regulatory response that includes Treg cells, IL-10, TGF-β, changes in effector-cell activation, and altered antibody quality. An increase in allergen-specific IgG4 is therefore best regarded as a mechanistic or pharmacodynamic marker rather than a routinely accepted stand-alone surrogate of individual clinical AIT efficacy. Clinical response must be assessed using symptoms, medication use, provocation outcomes where appropriate, and disease control [32].
4.3. Hygiene Hypothesis and Microbiome-Based Immune Regulation
A theory explaining the increasing prevalence of allergic diseases is the hygiene hypothesis, which proposes that microbial exposure during early life plays an important role in immune system development [34,35]. According to this hypothesis, exposure to diverse microorganisms and environmental antigens during childhood maintains the balance between Th1 and Th2 immune responses, thereby reducing the incidence of allergic diseases [35].
Companion animals may influence the microbial characteristics of indoor environments because pets are among the sources contributing to indoor microbial communities [36]. Indoor microbial exposure has been associated with allergic and inflammatory diseases, although the direction and magnitude of these associations vary across studies [36]. Such microbial exposures may influence allergic disease through multiple immunological mechanisms, including modulation of Th2-associated responses and regulatory immune pathways [35]. However, these effects are not consistently protective, and the relationship between microbial exposure and allergic disease appears to be context-dependent [35,36].
The diversity and composition of indoor microbial communities are influenced by multiple environmental and anthropogenic factors, including building characteristics, ventilation, occupancy, and occupant lifestyles [36]. Similarly, the relationship between companion animal exposure and allergic disease is not uniform. Early exposure to dogs has been associated with a reduced likelihood of sensitization in some studies, whereas findings for cat exposure have been inconsistent, and the timing and level of exposure may influence these outcomes [4]. Therefore, companion animal exposure should be understood within a broader environmental and immunological context rather than as uniformly protective or harmful.
5. Exposure and Transmission
5.1. Direct Exposure
Exposure may occur through direct physical contact with an animal or indirectly through allergen-containing material in a shared indoor environment. These exposure situations do not result in equivalent exposure levels, because actual exposure varies with the intensity and pattern of exposure and the characteristics of the indoor environment [4,37].
When companion animals are kept indoors, allergens can accumulate on textile surfaces, such as carpets, bedding, and sofas, which may function as allergen reservoirs [26]. These accumulated allergens may become airborne following environmental disturbance, resulting in intermittent or repeated inhalation exposure rather than a constant airborne concentration. Such repeated exposure may contribute to symptom elicitation in sensitized individuals, whereas the development of sensitization depends on multiple host- and exposure-related factors [3,4]. In addition, occupational groups with frequent animal contact, including veterinarians and animal-care workers, may experience substantial allergen exposure and an increased risk of work-related allergic symptoms [10].
5.2. Indirect Exposure
Indirect exposure refers to exposure pathways through which allergens are encountered even in environments where companion animals are not directly kept or contacted. Pet-derived allergens can be readily transported through various carriers such as human clothing, shoes, hair, and bags, and this kind of passive transfer contributes to widespread contamination of indoor environments [10,38]. Cat allergens have been found in school classrooms without cats at concentrations higher than those found in homes without cats but lower than those found in homes with cats [7]. For example, Fel d 1 and Can f 1 have been detected in school dust, including in environments where cats or dogs had no direct access, demonstrating the potential for indirect transfer of cat- and dog-derived allergens [39].
Pet-derived allergens have been detected in other public facilities such as public transportation systems, hospitals, hotels, and offices, potentially leading to persistent low-level exposure even among individuals without direct contact with companion animals [3]. Such indirect exposure may trigger symptoms particularly in sensitive individuals and represents a major factor complicating exposure avoidance strategies. Moreover, indirect exposure may also facilitate long-range transport through association with airborne fine particles [10]. This indicates that allergens are not confined to specific spaces but may exist across different environments.
5.3. Exposure Levels
Environmental studies have reported Fel d 1 and Can f 1 concentrations in settled house dust in relation to sensitization and asthma, but reported exposure levels should not be interpreted as universal biological thresholds. In a study of 12–14-year-old schoolchildren in Los Alamos, New Mexico, Fel d 1 and Can f 1 were measured in settled house dust using two-site immunoassays. Fel d 1 concentrations of ≥8 μg/g dust and Can f 1 concentrations of ≥10 μg/g dust were used to characterize relatively high household exposure; however, current household allergen concentrations were not clearly associated with sensitization or symptoms in individual children [40]. Thus, these values should be interpreted as study-specific exposure levels rather than universal clinical thresholds.
Exposure–response relationships vary according to the study population, individual susceptibility, exposure setting, sampling method, analytical approach, and clinical outcome. The persistence of detectable allergen in dust or on surfaces indicates environmental reservoirs, but detection alone does not establish clinically relevant exposure or symptomatic disease [37].
6. Cross-Reactivity and Polysensitization
6.1. Cross-Reactivity
Immunological cross-reactivity, in which proteins from different species are similarly recognized by IgE antibodies, frequently occurs across species [3,25]. Such cross-reactivity represents a major factor complicating the diagnosis and treatment of allergic diseases [41,42].
Cross-reactivity requires shared IgE-recognized epitopes and should be distinguished from simple membership in the same protein family. Structural homology can provide a molecular basis for cross-reactivity, but homology alone does not demonstrate IgE cross-reactivity, and IgE cross-reactivity does not necessarily translate into clinically relevant cross-allergy. These distinctions are particularly important for lipocalins and serum albumins [3,42].
A representative example is the cross-reactivity between the cat allergen Fel d 2 (serum albumin) and porcine Sus s 1 (serum albumin), which underlies pork-cat syndrome. IgE inhibition studies have shown that sensitization to cat serum albumin can represent the primary event, with subsequent cross-reactivity to porcine serum albumin and allergic reactions following pork consumption [13].
Several mammalian lipocalins show sequence and structural similarity. For example, IgE cross-reactivity between Fel d 4 and Can f 6 has been demonstrated in molecular studies [22,43]. In clinical interpretation, however, a positive IgE result to both components can reflect true co-sensitization, cross-reactive IgE, or both. Thus, IgE positivity should not be interpreted as a false-positive result solely because the original sensitizing source or clinical relevance remains uncertain.
Another example is the IgE cross-reactivity between the dog allergen Can f 5 and human prostate-specific antigen (PSA), both members of the kallikrein protein family. The clinical relevance of this cross-reactivity has been demonstrated in a case of human seminal plasma allergy [44]. This finding suggests that pet-derived allergens can also cross-react with homologous human proteins. Such diverse cross-reactivities complicate the identification of the true causative allergen, and conventional extract-based diagnostic methods are limited in their ability to distinguish these differences [2,4]. Therefore, CRD can help distinguish cross-reactivity from genuine sensitization [3].
Figure 3 distinguishes three levels of evidence in molecular allergology: protein-family or sequence homology, experimentally demonstrated IgE cross-reactivity, and clinically relevant cross-allergy supported by exposure–response concordance. This framework prevents structural similarity from being interpreted as proof of clinical cross-reactivity.
6.2. Polysensitization
Polysensitization refers to IgE sensitization to multiple allergen sources or molecular components and may reflect co-sensitization, cross-reactive IgE, or a combination of both [3]. Some cohorts have associated broader molecular sensitization profiles with asthma and greater disease severity; however, sensitization profiles alone do not establish clinical severity or relevance [3,8]. Interpretation should therefore consider the magnitude and molecular pattern of IgE sensitization together with exposure history, symptom timing, comorbidities, and clinical phenotype [3].
CRD can refine the characterization of a polysensitized patient by identifying the particular molecular components recognized by IgE. It may help distinguish primary sensitization from potential cross-reactivity, but it does not by itself establish which allergen causes symptoms. The results must therefore be integrated with exposure history and symptom timing and, when clinical relevance remains uncertain, with provocation testing or other functional assays [3,8].
Polysensitization may arise from complex interactions among exposure to multiple allergens, cross-reactivity, and immune responses. Therefore, evaluation and treatment of patients with animal allergies require approaches that consider the presence of sensitization as well as the underlying mechanisms and clinical significance of that sensitization.
7. Clinical Manifestations
7.1. Respiratory Diseases
Clinically relevant cat and dog allergy most commonly presents with allergic rhinitis, conjunctivitis, and/or asthma in sensitized individuals with a compatible exposure history [29]. These reactions occur after allergen-containing carrier particles or contaminated material reach the upper or lower airways or ocular mucosa; they should not be described as a consequence of a single fixed “allergen particle size” [3,4].
Allergic rhinitis is the most common clinical manifestation and is characterized by symptoms such as sneezing, rhinorrhea, nasal congestion, and nasal itching. These symptoms result from IgE-mediated inflammatory reactions and mast cell degranulation within the nasal mucosa and may progress to chronic inflammatory conditions with repeated exposure [45]. In particular, the major cat allergen Fel d 1 is readily airborne, with a substantial fraction carried on small particles that can remain suspended for prolonged periods [26].
Bronchial asthma represents a more severe respiratory disease characterized by airway inflammation, airway narrowing, excessive mucus secretion, and airway hyperresponsiveness [31]. In sensitized patients, repeated exposure can induce airway epithelial damage and infiltration of immune cells, which may lead to chronic inflammation and structural remodeling [30]. In genetically predisposed individuals, sensitization to pet-derived allergens has been associated with an increased risk of asthma development, whereas early-life exposure to companion animals may, under certain conditions, be associated with a reduced risk of subsequent allergic sensitization [4,46].
Exposure to cat allergens may induce both early and late asthmatic responses. In cat-allergic patients with asthma, late asthmatic responses following allergen challenge may occur up to 24 h after exposure [47].
Dog allergen sensitization has been associated with asthma severity in children. In particular, sensitization to Can f 2 and broader multisensitization to animal-derived lipocalins has been reported more frequently in children with severe asthma than in those with controlled asthma [48,49].
7.2. Cutaneous and Systemic Allergic Reactions
Dog- and cat-derived allergens may induce cutaneous and systemic reactions. A representative cutaneous manifestation is atopic dermatitis, which results from combined abnormalities in skin barrier function and immunological responses [50]. Atopic dermatitis is characterized by symptoms such as pruritus, erythema, xerosis, and lichenification, and may be triggered by inhalant allergens in susceptible individuals [50]. Exposure to allergens such as Fel d 1 may trigger an immune response [4]. Allergic conjunctivitis is also a common manifestation and is characterized by ocular itching, conjunctival redness, and increased tear secretion. This condition results from IgE-mediated reactions and mast cell activation within conjunctival tissues [29].
Systemic reactions attributable to cat or dog allergens appear to be uncommon compared with respiratory and ocular manifestations. Anaphylaxis represents a rare clinical manifestation of cat or dog allergy. When anaphylaxis occurs, it is potentially life-threatening and requires immediate treatment [51]. In addition, systemic reactions may occur in some patients through clinically relevant cross-reactivity between pet-derived and food allergens [13,42].
7.3. Factors Influencing Disease Severity and Clinical Heterogeneity
Clinical manifestations of cat and dog allergy show substantial heterogeneity among patients, reflecting the influence of multiple host-, exposure-, and allergen-related factors [3]. Sensitization to individual allergen components may be associated with distinct clinical phenotypes; for example, monosensitization to Can f 5 has been associated with selective clinical reactivity to male rather than female dogs [52]. However, associations between sensitization to individual allergen components or polysensitization and clinical severity should be interpreted probabilistically rather than deterministically. Neither sensitization to a single component, such as Fel d 1 or Can f 5, nor polysensitization alone should be regarded as a direct measure of symptom severity [3].
Genetic susceptibility, allergen exposure, and environmental factors such as air pollution can influence clinical manifestations and disease severity [30]. In particular, environmental exposures during infancy may influence subsequent allergic sensitization and the risk of allergic disease later in childhood [46]. For precision management, molecular sensitization profiles should be interpreted together with the patient’s clinical phenotype, inflammatory response pattern, and exposure history rather than used in isolation [3].
8. Diagnosis
8.1. Traditional Diagnostic Methods
Diagnosis of human allergy to cats or dogs requires concordance among a compatible clinical history, relevant exposure, and evidence of IgE sensitization [53]. Skin prick testing and serum allergen-specific IgE testing remain first-line tools for documenting sensitization, but a positive test does not by itself establish that the animal exposure is the cause of symptoms. Table 2 summarizes conventional and molecular approaches and emphasizes their complementary roles rather than ranking CRD as inherently more clinically specific.
Serum-specific IgE assays quantitatively measure IgE antibodies against specific allergens in patient blood samples and are used as alternatives when SPT is difficult to perform, such as in patients with skin diseases or those taking antihistamines [54]. Standardized methods such as ImmunoCAP provide high reproducibility and objectivity and enable quantitative comparison among various allergens [54].
Despite their widespread use, these conventional extract-based diagnostic methods have several limitations. First, allergen extracts consist of complex mixtures of proteins and therefore cannot distinguish individual allergen components, making it difficult to differentiate cross-reactivity from genuine sensitization [3]. For example, IgE responses to common proteins such as serum albumins may appear as cross-reactivity among different animal species, thereby obscuring the true sensitizing source [42]. Second, the composition of allergen extracts may vary substantially depending on manufacturing processes and source materials, resulting in limitations in standardization [2,3,4].
Third, results from SPT and specific IgE assays do not always correspond directly with clinical symptoms. In other words, sensitization may be present without clinical allergy [29]. This indicates that exposure history and symptom patterns must always be considered together during diagnosis. Furthermore, in the case of pet-derived allergens, many patients exhibit polysensitization patterns involving simultaneous reactions to multiple animals or allergens, making it difficult to identify the precise causative allergen using extract-based methods alone [2,3,4].
8.2. Molecular Diagnosis (CRD)
Component-resolved diagnosis (CRD) measures IgE to individual allergen molecules and can refine a sensitization profile beyond whole-extract testing [2,8]. It is particularly useful for identifying species-associated marker components and for recognizing patterns compatible with serum-albumin or lipocalin cross-reactivity. Nevertheless, CRD does not independently establish clinical causality, and its results should be interpreted together with the patient’s clinical history and relevant exposure information [42].
Associations between individual allergen components, polysensitization patterns, asthma, and disease severity have been reported; however, the role of allergenic molecules as predictors of disease severity requires further investigation [8]. CRD may therefore contribute to patient characterization and diagnostic clarification, but should not be used as a stand-alone predictor of disease severity or determinant of treatment.
When extract tests, component results, exposure history, and symptoms are discordant, additional evaluation may be considered in specialist practice. Controlled nasal allergen provocation can help establish the clinical relevance of sensitization in selected patients, while basophil activation testing may provide additional functional diagnostic information when conventional diagnostic approaches are inconclusive or conflicting [55,56]. These tests are not required routinely, but they illustrate the distinction between demonstrating sensitization and establishing clinically relevant allergy.
CRD is limited by the component repertoire of each platform, assay-specific performance, cost, accessibility, and the expertise required to interpret complex profiles. Accordingly, CRD should complement—not replace—clinical history, examination, and conventional allergy testing. Its contribution to personalized management is primarily to refine molecular sensitization profiles and patient classification, while treatment decisions should remain based on the overall clinical context rather than on CRD results alone [8].
9. Treatment and Management
9.1. Allergen Avoidance
Management begins by reducing clinically relevant exposure where feasible, but allergen avoidance should not be described as universally definitive or sufficient. The practical objective is to reduce exposure to an allergen that is both immunologically and clinically relevant, while recognizing the social and emotional consequences of pet removal. Because allergen reservoirs can persist after an animal is removed, environmental exposure may continue and additional environmental measures may still be required [26]. Decisions should be individualized according to disease severity, exposure–response concordance, and patient preferences. The principal management strategies for pet allergy, together with their advantages and limitations, are summarized in Table 3.
9.2. Environmental Control
Environmental control can reduce measured concentrations of airborne or reservoir allergens, but a reduction in allergen concentration does not necessarily produce an equivalent clinical improvement [37,57]. HEPA filtration, reservoir reduction, cleaning, and bedroom exclusion can be considered as parts of a multimodal strategy. Their clinical effectiveness varies with adherence, baseline exposure, room characteristics, and the dominant route of exposure; therefore, environmental allergen reduction and patient-centered clinical benefit should be reported as distinct outcomes.
Regular cleaning may help reduce allergen accumulation within the environment. In particular, bedding, curtains, and carpets are surfaces prone to allergen accumulation [26]. However, conventional vacuum cleaners may resuspend allergens into the air, and therefore tools equipped with HEPA filters are recommended.
Behavioral measures such as restricting animal access to bedrooms, handwashing after contact, and selected cleaning or grooming practices may contribute to lower exposure, but generally provide partial rather than complete reduction. Recommendations should be tailored to the individual and should not imply that lowering a measured environmental allergen concentration guarantees symptom control.
9.3. Standard Pharmacotherapy
Standard pharmacotherapy remains central to the treatment of symptomatic cat and dog allergy and should be selected according to the affected organ system and disease severity. Options include second-generation H1 antihistamines for allergic rhinitis and conjunctival symptoms and intranasal corticosteroids for persistent allergic rhinitis [58]. For patients with asthma, treatment should follow current asthma guidelines and include inhaled corticosteroid (ICS)-containing therapy; treatment with as-needed short-acting β2-agonist (SABA) alone is not recommended [59]. These medications treat the patient’s inflammatory and symptomatic disease but do not eliminate sensitization or environmental allergen exposure; therefore, pharmacotherapy should be integrated with exposure management and, in selected patients, allergen immunotherapy or biologic treatment.
9.4. Allergen Immunotherapy
Allergen immunotherapy (AIT) aims to induce durable immunological tolerance through repeated administration of clinically relevant allergen preparations [28,32]. Its use in cat and dog allergy requires careful patient selection, confirmation that the animal allergen is clinically relevant, and attention to the composition and standardization of the extract.
AIT is associated with changes in T-cell regulation, effector-cell responsiveness, allergen-specific IgE, and blocking antibodies such as IgG4. Increased IgG4 can accompany successful AIT but should not be used as an individual surrogate of clinical efficacy. Clinical benefit must be evaluated by validated symptom, medication, and disease-control outcomes.
Evidence should be considered separately for cat and dog allergen immunotherapy. Controlled studies using standardized cat extracts have demonstrated benefit in selected cat-allergic patients, including reduced symptoms during cat exposure and decreased cat-specific bronchial responsiveness [60,61]. The evidence base for dog AIT is less convincing because dog extracts are molecularly heterogeneous, standardization is challenging, and the number of high-quality randomized controlled trials is limited [4,53]. Consequently, efficacy should not be generalized from cat AIT to dog AIT or from better-established indications such as house dust mite or pollen allergy.
Despite its benefits, AIT requires long-term treatment, typically for 3–5 years, and is also limited by cost and patient compliance [29,62]. Some patients may experience local or systemic adverse reactions during treatment, and rare cases of anaphylaxis have also been reported [28]. Various approaches including sublingual immunotherapy, in addition to conventional subcutaneous immunotherapy, have been developed, and research aimed at improving patient convenience and safety continues.
9.5. Novel Therapeutic Strategies
Source-directed allergen-neutralization strategies are of interest because they aim to reduce exposure without removing the animal. Diets containing egg-derived anti-Fel d 1 IgY have been shown to reduce immunologically active Fel d 1 in cat saliva or on hair [63]. However, reduction in active Fel d 1 is an allergen-exposure outcome and should not be equated with proven clinical benefit in allergic people; evidence demonstrating clinically meaningful improvement in patient symptoms remains limited.
A clinically distinct passive immunotherapy strategy uses two fully human Fel d 1-neutralizing IgG4 monoclonal antibodies, REGN1908 and REGN1909, administered directly to the allergic patient rather than reducing allergen production at the animal source. In a randomized, double-blind, placebo-controlled trial, a single dose of REGN1908–1909 reduced nasal symptoms after controlled cat-allergen challenge and inhibited IgE-mediated and type 2 inflammatory responses [64]. A subsequent randomized environmental-exposure-unit study in cat-allergic patients with mild asthma found that a single 600 mg dose significantly attenuated allergen-induced FEV1 reductions and early asthmatic responses for up to 85 days [65]. These findings provide proof of concept for passive Fel d 1 neutralization in humans, but this patient-directed monoclonal-antibody approach is mechanistically and clinically distinct from source-directed anti-Fel d 1 IgY diets.
Recombinant or modified Fel d 1 molecules and peptide-based approaches are being investigated as strategies to improve the specificity or tolerability of immunotherapy [66]. Biologic therapies such as anti-IgE therapy are established for defined clinical indications, including selected patients with severe allergic asthma, but should not be presented as general treatments for cat or dog sensitization [67].
Other approaches, including peptide-based immunotherapy and allergen-neutralizing strategies, remain investigational [63,66]. Their clinical value requires controlled trials demonstrating patient-centered outcomes as distinct from laboratory evidence of immunological change or allergen reduction.
Animal allergies cannot be adequately managed using a single approach alone, and multifaceted strategies integrating allergen avoidance, environmental control, immunotherapy, and emerging therapeutic approaches may be required. Personalized management strategies that integrate molecular sensitization profiles with clinical manifestations, exposure history, and disease severity may support more individualized clinical decision-making. For example, molecular diagnostic approaches such as CRD may refine molecular sensitization profiles and provide complementary information for individualized clinical decision-making when interpreted together with exposure history and clinical phenotype [3].
10. Conclusions
Human allergy to cats and dogs is clinically important, but population-level trends in pet ownership, urbanization, or indoor living should not be interpreted as direct proof of a corresponding increase in allergic disease. These societal factors can modify opportunities for exposure, whereas sensitization and symptomatic allergy arise from interactions among allergen dose and timing, molecular sensitization, host susceptibility, barrier and immune responses, and disease phenotype.
Cat- and dog-derived allergenic proteins can persist in dust and be transported into environments without resident animals, but environmental detection does not necessarily indicate a clinically relevant exposure for every individual. Similarly, polysensitization may be associated with more complex phenotypes in some cohorts, yet the number of positive IgE responses alone does not determine disease severity. Clinical interpretation requires molecular sensitization profiles to be linked with symptoms, exposure patterns, and individual immune and airway characteristics.
Molecular allergology has improved the characterization of cat and dog sensitization and can help distinguish species-associated marker sensitization from patterns compatible with cross-reactivity. CRD is therefore a valuable diagnostic support tool, but it does not independently establish the causal allergen or dictate treatment. Where uncertainty persists, exposure–response concordance and, in selected specialist settings, provocation or functional testing can provide additional evidence.
Management is best framed as a layered strategy that combines clinically appropriate pharmacotherapy with feasible exposure reduction and, for selected patients, allergen immunotherapy or disease-specific biologic treatment. Evidence for cat AIT is more established than for dog AIT, and emerging source-control approaches such as anti-Fel d 1 IgY should be evaluated separately for allergen reduction and for patient-centered clinical benefit. Future research should prioritize standardized molecular exposure assessment, prospective linkage of component profiles to clinical phenotypes, high-quality dog-AIT trials, and intervention studies that measure both environmental allergen reduction and meaningful symptom outcomes.
A precision approach to cat and dog allergy therefore depends less on any single test or exposure measurement than on the integration of molecular sensitization, exposure–response relationships, inflammatory phenotype, and patient-centered outcomes.