Min Jin-Young, Nayak Jayakar V, Hulse Kathryn E, Stevens Whitney W, Raju Paul A, Huang Julia H, Suh Lydia A, Van Roey Griet A, Norton James E, Carter Roderick G, Price Caroline P E, Weibman Ava R, Rashan Ali R, Ghosn Eliver E, Patel Zara M, Homma Tetsuya, Conley David B, Welch Kevin C, Shintani-Smith Stephanie, Peters Anju T, Grammer Leslie C, Harris Kathleen E, Kato Atsushi, Hwang Peter H, Kern Robert C, Herzenberg Leonore A, Schleimer Robert P, Tan Bruce K
Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, Calif.
J Allergy Clin Immunol. 2017 Dec;140(6):1562-1571.e5. doi: 10.1016/j.jaci.2017.05.032. Epub 2017 Jun 16.
IgD is an enigmatic antibody isotype best known when coexpressed with IgM on naive B cells. However, increased soluble IgD (sIgD) levels and increased IgDIgM B-cell populations have been described in the human upper respiratory mucosa.
We assessed whether levels of sIgD and IgD B cell counts are altered in nasal tissue from patients with chronic rhinosinusitis (CRS). We further characterized IgD B-cell populations and explored clinical and local inflammatory factors associated with tissue sIgD levels.
sIgD levels were measured by means of ELISA in nasal tissues, nasal lavage fluid, sera, and supernatants of dissociated nasal tissues. IgD cells were identified by using immunofluorescence and flow cytometry. Inflammatory mediator levels in tissues were assessed by using real-time PCR and multiplex immunoassays. Bacterial cultures from the middle meatus were performed. Underlying medical history and medicine use were obtained from medical records.
sIgD levels and numbers of IgD cells were significantly increased in uncinate tissue (UT) of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with that of control subjects (4-fold, P < .05). IgD cells were densely scattered in the periglandular regions of UT from patients with CRSsNP. We also found that IgDCD19CD38 plasmablast numbers were significantly increased in tissues from patients with CRSsNP compared with control tissues (P < .05). Among numerous factors tested, IL-2 levels were increased in UT from patients with CRSsNP and were positively correlated with tissue IgD levels. Additionally, supernatants of IL-2-stimulated dissociated tissue from patients with CRSsNP had significantly increased sIgD levels compared with those in IL-2-stimulated dissociated control tissue ex vivo (P < .05). Tissue from patients with CRS with preoperative antibiotic use or those with pathogenic bacteria showed higher IgD levels compared with tissue from patients without these variables (P < .05).
sIgD levels and IgDCD19CD38 plasmablast counts were increased in nasal tissue of patients with CRSsNP. IgD levels were associated with increased IL-2 levels and the presence of pathogenic bacteria. These findings suggest that IgD might contribute to enhancement mucosal immunity or inflammation or respond to bacterial infections in patients with CRS, especially CRSsNP.
IgD是一种神秘的抗体亚型,在未成熟B细胞上与IgM共表达时最为人所知。然而,人类上呼吸道黏膜中可溶性IgD(sIgD)水平升高以及IgD⁺IgM⁺ B细胞群体增加已有相关报道。
我们评估了慢性鼻窦炎(CRS)患者鼻组织中sIgD水平和IgD⁺ B细胞计数是否发生改变。我们进一步对IgD⁺ B细胞群体进行了特征分析,并探讨了与组织sIgD水平相关的临床和局部炎症因子。
采用酶联免疫吸附测定(ELISA)法检测鼻组织、鼻腔灌洗液、血清及解离鼻组织上清液中的sIgD水平。利用免疫荧光和流式细胞术鉴定IgD⁺细胞。采用实时聚合酶链反应(PCR)和多重免疫测定法评估组织中的炎症介质水平。对中鼻道进行细菌培养。从病历中获取患者的既往病史和用药情况。
与对照组相比,无鼻息肉的慢性鼻窦炎(CRSsNP)患者钩突组织(UT)中的sIgD水平和IgD⁺细胞数量显著增加(4倍,P < 0.05)。在CRSsNP患者的UT腺周区域,IgD⁺细胞密集分布。我们还发现,与对照组织相比,CRSsNP患者组织中的IgD⁺CD19⁺CD38⁺浆母细胞数量显著增加(P < 0.05)。在检测的众多因素中,CRSsNP患者UT中的白细胞介素-2(IL-2)水平升高,且与组织IgD水平呈正相关。此外,与体外IL-2刺激的解离对照组织相比,CRSsNP患者IL-2刺激的解离组织上清液中的sIgD水平显著升高(P < 0.05)。术前使用抗生素的CRS患者或有病原菌的患者的组织与无这些变量的患者的组织相比,IgD水平更高(P < 0.05)。
CRSsNP患者鼻组织中的sIgD水平和IgD⁺CD19⁺CD38⁺浆母细胞计数增加。IgD水平与IL-2水平升高和病原菌的存在有关。这些发现表明,IgD可能有助于增强CRS患者,尤其是CRSsNP患者的黏膜免疫或炎症反应,或对细菌感染作出反应。