Humbert M, Durham S R, Ying S, Kimmitt P, Barkans J, Assoufi B, Pfister R, Menz G, Robinson D S, Kay A B, Corrigan C J
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London.
Am J Respir Crit Care Med. 1996 Nov;154(5):1497-504. doi: 10.1164/ajrccm.154.5.8912771.
Intrinsic (nonatopic) asthma is considered to be a distinct pathogenetic variant of asthma since, unlike extrinsic (atopic) asthma, patients with the disease are skin test-negative to common aeroallergens, and have total serum IgE concentrations within the normal range. Nevertheless, the recent demonstration of increased numbers of cells expressing the high-affinity IgE receptor in bronchial biopsies from atopic and nonatopic asthmatic subjects, together with epidemiologic evidence indicating that serum IgE concentrations relate closely to asthma prevalence regardless of atopic status, suggests that IgE-mediated mechanisms may participate in the pathogenesis of both atopic and nonatopic asthma. Furthermore both variants of the disease are associated with bronchial mucosal eosinophilic inflammation. Interleukin-4 (IL-4) is an essential cofactor for IgE synthesis, and there is strong evidence that IL-5 plays a major role in eosinophil accumulation in asthmatic inflammation. For these reasons we compared the expression of IL-4 and IL-5 mRNA and protein product using a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) amplification, in situ hybridization, and immunohistochemistry in bronchial biopsies from symptomatic atopic and nonatopic asthmatic subjects and atopic and nonatopic controls. The results showed that as compared with controls, biopsies from both groups of asthmatic subjects had increased numbers of IL-4 and IL-5 mRNA copies relative to beta-actin mRNA as detected by RT-PCR. Similarly, in situ hybridization and immunohistochemistry demonstrated increased numbers of cells expressing IL-4 and IL-5 mRNA and protein in asthmatic subjects, irrespective of their atopic status. We conclude that individuals with either atopic or nonatopic asthma show infiltration of the bronchial mucosa with cells expressing Th2-type cytokines, providing further evidence for similarities in the immunopathogenesis of these clinically distinct forms of asthma.
内因性（非特应性）哮喘被认为是哮喘的一种独特的发病机制变体，因为与外因性（特应性）哮喘不同，患有这种疾病的患者对常见气传变应原的皮肤试验呈阴性，且血清总IgE浓度在正常范围内。然而，最近在特应性和非特应性哮喘患者的支气管活检中发现表达高亲和力IgE受体的细胞数量增加，同时流行病学证据表明血清IgE浓度与哮喘患病率密切相关，而与特应性状态无关，这表明IgE介导的机制可能参与了特应性和非特应性哮喘的发病过程。此外，该疾病的两种变体均与支气管黏膜嗜酸性粒细胞炎症有关。白细胞介素-4（IL-4）是IgE合成的必需辅助因子，并且有强有力的证据表明IL-5在哮喘炎症中嗜酸性粒细胞的积聚中起主要作用。基于这些原因，我们使用半定量逆转录聚合酶链反应（RT-PCR）扩增、原位杂交和免疫组织化学，比较了有症状的特应性和非特应性哮喘患者以及特应性和非特应性对照者支气管活检中IL-4和IL-5 mRNA及蛋白产物的表达。结果显示，与对照组相比，通过RT-PCR检测发现两组哮喘患者活检标本中相对于β-肌动蛋白mRNA，IL-4和IL-5 mRNA拷贝数均增加。同样，原位杂交和免疫组织化学显示，无论特应性状态如何，哮喘患者中表达IL-4和IL-5 mRNA及蛋白的细胞数量均增加。我们得出结论，患有特应性或非特应性哮喘的个体均表现出支气管黏膜有表达Th2型细胞因子的细胞浸润，这为这些临床特征不同的哮喘形式在免疫发病机制上的相似性提供了进一步证据。
