Shin Seung-Heon, Ponikau Jens U, Sherris David A, Congdon David, Frigas Evangelo, Homburger Henry A, Swanson Mark C, Gleich Gerald J, Kita Hirohito
Department of Internal Medicine, Mayo Clinic Rochester, Rochester, MN 55905, USA.
J Allergy Clin Immunol. 2004 Dec;114(6):1369-75. doi: 10.1016/j.jaci.2004.08.012.
Chronic rhinosinusitis (CRS) is one of the most common long-term illnesses in the United States. The etiology of CRS is unknown, and no effective treatment has been established.
We investigated the hypothesis that abnormal immunologic responses to ubiquitous airborne fungi contribute to the pathogenesis of this disease.
The proliferative and cytokine responses of PBMCs to extracts from 4 common airborne fungi-including Alternaria , Aspergillus , Cladosporium , and Penicillium -were examined by in vitro culture. Serum specimens were tested for specific IgE and IgG to these fungi.
PBMCs from approximately 90% of the patients with CRS, but not those from normal individuals, produced both IL-5 and IL-13 when exposed to Alternaria. Furthermore, PBMCs from patients with CRS produced significantly more IFN-gamma than PBMCs from normal individuals in response to Alternaria (median, 553 pg/mL vs 98 pg/mL; P < .01). Levels of serum IgG antibodies to Alternaria and Cladosporium were clearly increased in patients with CRS compared with normal individuals ( P < .01). Less than 30% of the patients with CRS had specific IgE antibodies to Alternaria or Cladosporium. The increased humoral (serum IgG) response strongly correlated with the increased cellular (IL-5 production) response to Alternaria ( r = 0.619; P < .01).
Patients with CRS show exaggerated humoral and cellular responses, both T(H)1 and T(H)2 types, to common airborne fungi, particularly Alternaria. The anomalous immune and inflammatory responses to ubiquitous fungi may explain the chronicity of airway inflammation in CRS.
慢性鼻-鼻窦炎(CRS)是美国最常见的长期疾病之一。CRS的病因尚不清楚,且尚未确立有效的治疗方法。
我们研究了以下假设,即对普遍存在的气传真菌的异常免疫反应促成了该疾病的发病机制。
通过体外培养检测外周血单核细胞(PBMCs)对4种常见气传真菌(包括链格孢属、曲霉属、枝孢属和青霉属)提取物的增殖和细胞因子反应。检测血清标本中针对这些真菌的特异性IgE和IgG。
约90%的CRS患者的PBMCs在暴露于链格孢属时产生IL-5和IL-13,而正常个体的PBMCs则不产生。此外,CRS患者的PBMCs在对链格孢属的反应中产生的干扰素-γ明显多于正常个体(中位数分别为553 pg/mL和98 pg/mL;P <.01)。与正常个体相比,CRS患者中针对链格孢属和枝孢属的血清IgG抗体水平明显升高(P <.01)。不到30%的CRS患者对链格孢属或枝孢属有特异性IgE抗体。体液(血清IgG)反应的增强与对链格孢属的细胞(IL-5产生)反应的增强密切相关(r = 0.619;P <.01)。
CRS患者对常见气传真菌,特别是链格孢属,表现出过度的体液和细胞反应,包括Th1和Th2型。对普遍存在的真菌的异常免疫和炎症反应可能解释了CRS气道炎症的慢性化。