Department of Immunotechnology, Lund University, Lund, Sweden.
Clin Exp Allergy. 2011 Jun;41(6):811-20. doi: 10.1111/j.1365-2222.2011.03724.x. Epub 2011 Mar 29.
The role of allergy in the aetiopathogenesis of chronic rhinosinusitis (CRS) remains controversial. For example, in some cases with sinus fungal infections allergy can be demonstrated by standard tests. In other cases, such signs can be absent despite elevated levels of IgE-positive cells in sinus tissue and the presence of IgE and eosinophils in the sinus mucous.
To define the nature of molecular diversity in antibodies of the IgE isotype at the site of local inflammation in subjects diagnosed with non-allergic fungal eosinophilic sinusitis (NAFES).
The local occurrence and sequence characteristics of IgE-encoding transcripts in NAFES patients were investigated and compared with sequences found in subjects diagnosed with CRS featuring systemic allergy. These sequences have also been compared with other reported IgE-encoding transcriptomes. Results IGHV genes derived from major subgroups 1, 3, 4 and 5 and a diverse set of IGHD and IGHJ genes were shown to create the IgE repertoire in patients diagnosed with NAFES and CRS. The average lengths of the third hypervariable loop in these populations were 15.8 and 14.6 residues. The sequences showed evidence of extensive somatic hypermutation (mutation frequency: NAFES, 6.4 ± 3.2%; CRS, 7.0 ± 4.4%) with substitutions targeted to complementarity-determining regions. These sequence collections thus show extensive similarities to those found in other polyclonal Ig repertoires including those encoding IgE.
We conclude that sinus IgE-encoding transcripts in subjects diagnosed with NAFES show evidence of conventional IgE responses and we suggest that allergens with characteristics of classical antigens should be investigated for a role in the local response occurring in NAFES. This investigation illustrates that assessment of local immunity might be an important diagnostic tool in conditions like NAFES with no systemic signs of allergy to identify or rule out an allergic component of the patient's disease.
过敏在慢性鼻-鼻窦炎（CRS）的发病机制中的作用仍存在争议。例如，在某些鼻窦真菌感染的情况下，通过标准测试可以证明过敏的存在。在其他情况下，尽管鼻窦组织中 IgE 阳性细胞水平升高，且鼻窦黏膜中存在 IgE 和嗜酸性粒细胞，但仍可能没有这些迹象。
定义在诊断为非变应性真菌性嗜酸性鼻窦炎（NAFES）的患者局部炎症部位 IgE 同种型抗体的分子多样性的性质。
研究了 NAFES 患者中 IgE 编码转录本的局部发生和序列特征，并与诊断为伴有全身过敏的 CRS 的患者的序列进行了比较。这些序列也与其他报道的 IgE 编码转录组进行了比较。结果表明，源自主要亚群 1、3、4 和 5 的 IGHV 基因以及多种多样的 IGHD 和 IGHJ 基因，在诊断为 NAFES 和 CRS 的患者中创造了 IgE 库。这些群体中第三高变环的平均长度分别为 15.8 和 14.6 个残基。这些序列显示出广泛的体细胞超突变（突变频率：NAFES，6.4±3.2%；CRS，7.0±4.4%）的证据，突变针对互补决定区。这些序列集合因此与其他多克隆 Ig 库（包括编码 IgE 的库）的序列具有广泛的相似性。
我们得出结论，诊断为 NAFES 的患者的鼻窦 IgE 编码转录本显示出常规 IgE 反应的证据，我们建议应研究具有经典抗原特征的变应原，以确定其在 NAFES 局部反应中所起的作用。这项研究表明，评估局部免疫可能是一种重要的诊断工具，可用于无全身过敏迹象的 NAFES 等疾病，以确定或排除患者疾病的过敏成分。
