Salah Adeeb, Yoshifuji Hajime, Ito Shinji, Kitagori Koji, Kiso Kaori, Yamada Norishige, Nakajima Toshiki, Haga Hironori, Tsuruyama Tatsuaki, Miyagawa-Hayashino Aya
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Department of Pathology, Faculty of Medicine and Health Sciences, University of Science and Technology, Sana'a, Yemen.
Patholog Res Int. 2017;2017:9312142. doi: 10.1155/2017/9312142. Epub 2017 May 16.
Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan condition manifesting itself in different forms. This study aimed to investigate protein expression profiles and to find the possible biomarker for IgG4-RD by liquid chromatography mass spectrometry (LC-MS) using tissue sections in IgG4-RD patients.
Protein expression profiles in five IgG4-related pancreatitis and three normal pancreatic samples were compared using LC-MS and were validated by quantitative real-time PCR (qRT-PCR), immunoblotting, and immunohistochemistry. ELISA was employed in the serum of 20 patients with systemic IgG4-RD before and during steroid treatment.
LC-MS indicated that the levels of 17 proteins were significantly higher and 12 others were significantly lower in IgG4-related pancreatitis patients compared to controls. Among these proteins, galectin-3 levels were 13-fold higher in IgG4-related pancreatitis ( < 0.01). These results were confirmed by immunoblotting and qRT-PCR. The average number of galectin-3 + cells in various organs of IgG4-RD patients, including salivary glands, lungs, and lymph nodes, was higher than in controls. Galectin-3 was detectable in macrophages, dendritic cells, and stromal myofibroblast-like cells, but not in lymphocytes by immunofluorescence staining. Serum galectin-3 levels were higher in patients with IgG4-RD compared with healthy donors and remained high during steroid therapy.
Galectin-3 was overexpressed in IgG4-RD and the levels were indirectly related to clinical activity.
免疫球蛋白G4相关疾病（IgG4-RD）是一种以不同形式表现的多器官疾病。本研究旨在通过液相色谱质谱联用技术（LC-MS），利用IgG4-RD患者的组织切片，研究蛋白质表达谱并寻找IgG4-RD可能的生物标志物。
使用LC-MS比较5例IgG4相关性胰腺炎和3例正常胰腺样本中的蛋白质表达谱，并通过定量实时聚合酶链反应（qRT-PCR）、免疫印迹和免疫组织化学进行验证。采用酶联免疫吸附测定（ELISA）检测20例系统性IgG4-RD患者在类固醇治疗前后血清中的情况。
LC-MS表明，与对照组相比，IgG4相关性胰腺炎患者中17种蛋白质水平显著升高，另外12种显著降低。在这些蛋白质中，IgG4相关性胰腺炎患者中半乳糖凝集素-3水平高出13倍（<0.01）。免疫印迹和qRT-PCR证实了这些结果。IgG4-RD患者包括唾液腺、肺和淋巴结在内的各个器官中半乳糖凝集素-3阳性细胞的平均数高于对照组。通过免疫荧光染色发现，半乳糖凝集素-3在巨噬细胞、树突状细胞和基质肌成纤维细胞样细胞中可检测到，但在淋巴细胞中未检测到。与健康供体相比，IgG4-RD患者血清半乳糖凝集素-3水平更高，且在类固醇治疗期间仍保持较高水平。
半乳糖凝集素-3在IgG4-RD中过度表达，其水平与临床活动间接相关。
