High Expression of Galectin-3 in Patients with IgG4-Related Disease: A Proteomic Approach.

High Expression of Galectin-3 in Patients with IgG4-Related Disease: A Proteomic Approach.
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DOI:
10.1155/2017/9312142
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发表时间:
2017
期刊:
Pathology research international
影响因子:
--
通讯作者:
Miyagawa-Hayashino A
Miyagawa-Hayashino A
中科院分区:
其他
文献类型:
--
作者:
Salah A;Yoshifuji H;Ito S;Kitagori K;Kiso K;Yamada N;Nakajima T;Haga H;Tsuruyama T;Miyagawa-Hayashino A

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免疫球蛋白G4相关疾病(IgG 4-RD)是一种以不同形式表现的多器官疾病。本研究旨在研究蛋白质表达谱,并通过液相色谱质谱法(LC-MS)使用IgG 4-RD患者的组织切片寻找IgG 4-RD的可能生物标志物。 使用LC-MS比较了5例IgG 4相关胰腺炎和3例正常胰腺样本中的蛋白表达谱,并通过定量实时PCR(qRT-PCR)、免疫印迹和免疫组织化学进行了验证。应用酶联免疫吸附试验(ELISA)检测20例系统性IgG_4-RD患者激素治疗前及治疗中血清IgG_4-RD水平。 LC-MS表明,与对照组相比,IgG 4相关胰腺炎患者中17种蛋白质的水平显著升高,另外12种蛋白质的水平显著降低。在这些蛋白质中,半乳糖凝集素-3水平在IgG 4相关胰腺炎中高13倍(P < 0.01)。通过免疫印迹和qRT-PCR证实了这些结果。IgG 4-RD患者的各种器官(包括唾液腺、肺和淋巴结)中半乳糖凝集素-3+细胞的平均数量高于对照组。半乳糖凝集素-3在巨噬细胞、树突状细胞和间质肌纤维母细胞样细胞中可检测到,但在淋巴细胞中不能通过免疫荧光染色检测到。IgG 4-RD患者血清半乳糖凝集素-3水平高于健康供体,并在类固醇治疗期间保持较高水平。 半乳糖凝集素-3在IgG 4-RD中过表达,其水平与临床活性间接相关。
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 (P < 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.