目的:免疫球蛋白G4相关疾病(IgG4-RD)是一种影响多个器官的全身性炎症,包括胰腺,唾液腺,肺,肾脏,皮肤,和淋巴结。临床上,它的特征是血清IgG和IgG4水平升高以及IgG4阳性浆细胞的组织浸润,淋巴细胞,纤维化,和闭塞性静脉炎.IgG4-RD与Th2显性细胞因子的增加有关,导致嗜酸性粒细胞增多,血清IgG4升高和纤维化。一个显着特征是其对皮质类固醇治疗的良好反应。研究皮质类固醇治疗对LATY136F敲入小鼠嗅觉功能障碍的影响,其表现出Th2型IgG1(人IgG4的鼠同源物)的产生增加,并发生了与IgG4-RD患者相似的多器官组织病变。
方法:将LATY136F敲入小鼠(n=24)分为不同年龄接受泼尼松龙或生理盐水的组。使用环己酰亚胺的行为测试评估嗅觉功能。进行组织学和免疫组织化学分析以评估嗅觉上皮厚度以及成熟和未成熟嗅觉神经元的存在。
结果:与对照组相比,皮质类固醇治疗的小鼠表现出显著改善的嗅觉功能。组织学分析显示,与对照组相比,治疗组的嗅觉上皮厚度和成熟(嗅觉标记蛋白阳性)和未成熟(生长相关蛋白43阳性)嗅觉神经元显着增加。
结论:皮质类固醇治疗可有效改善LATY136F敲入小鼠的嗅觉功能障碍并促进嗅觉上皮再生,提示皮质类固醇治疗对存在嗅觉功能障碍的IgG4-RD患者的潜在治疗益处.然而,需要对未经治疗的患者进行局部鼻用类固醇治疗的进一步研究.结果支持进一步研究局部鼻类固醇疗法治疗未经治疗的患者的嗅觉功能障碍,可能影响全球IgG4-RD的临床实践和患者管理策略。
OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition affecting multiple organs, including the pancreas, salivary glands, lungs, kidneys, skin, and lymph nodes. Clinically, it is characterized by elevated serum IgG and IgG4 levels and tissue infiltration by IgG4-positive plasma cells, lymphocytes, fibrosis, and phlebitis obliterans. IgG4-RD is linked to increased Th2-dominant cytokines, contributing to eosinophilia, elevated serum IgG4, and fibrosis. A notable feature is its good response to corticosteroid therapy. To investigate the effects of corticosteroid treatment on olfactory dysfunction in LATY136F knock-in mice, which exhibited increased production of Th2-type IgG1 (the murine homolog of human IgG4) and developed multiorgan tissue lesions similar to those observed in IgG4-RD patients.
METHODS: LATY136F knock-in mice (n=24) were divided into groups that received prednisolone or saline at different ages. Olfactory function was assessed using a behavioral test with cycloheximide. Histological and immunohistochemical analyses were performed to evaluate the olfactory epithelium thickness as well as the presence of mature and immature olfactory neurons.
RESULTS: Corticosteroid-treated mice exhibited significantly improved olfactory function compared to the controls. Histological analysis revealed a significant increase in olfactory epithelium thickness and mature (olfactory marker protein-positive) and immature (growth-associated protein 43-positive) olfactory neurons in the treated groups compared with the control group.
CONCLUSIONS: Corticosteroid treatment effectively improved olfactory dysfunction and promoted olfactory epithelium regeneration in LATY136F knock-in mice, suggesting the potential therapeutic benefits of corticosteroid treatment for patients with IgG4-RD experiencing olfactory dysfunction. However, further research on topical nasal steroid therapy in untreated patients is warranted. The results support further investigation into topical nasal steroid therapies for treating olfactory dysfunction in untreated patients, potentially influencing clinical practice and patient management strategies for IgG4-RD globally.