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使用二维差异凝胶电泳 (2D-DIGE) 和质谱技术鉴定系统性红斑狼疮诊断的潜在生物标志物。

Identification of potential biomarkers for systemic lupus erythematosus diagnosis using two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry.

机构信息

a Department of Clinical and Toxicological Analysis, Faculty of Pharmacy , Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais , Brazil.

b Parasitology Department , Biological Sciences Institute (ICB), Universidade Federal de Minas Gerais (UFMG) , Belo Horizonte , Minas Gerais , Brazil.

出版信息

Autoimmunity. 2017 Jun;50(4):247-256. doi: 10.1080/08916934.2017.1344975. Epub 2017 Jul 4.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease of the connective tissue with a large spectrum of clinical manifestations. Immune deregulation leads to autoantibody and immune complexes overproduction, complement activation, and persistent tissue inflammation. Considering that the current diagnosis depends on the interpretation of the complex criteria established by the American College of Rheumatology and that the disease course is characterized by unpredictable activations and remissions, each patient develops different manifestations, and therefore, the discovery of specific biomarkers is urgently required. Therefore, this study aimed to identify putative biomarkers for active and inactive SLE potentially capable in distinguishing laboratorial SLE from other autoimmune diseases. The 2D-DIGE proteomics technique was used to evaluate the differential abundance of proteins between patients with active SLE, inactive SLE, patients with other autoimmune disease, and healthy individuals. Six proteins showed increased abundance in active SLE (A) and inactive SLE (I) compared to the C and O groups, but not between groups A and I. There were two transthyretin (TTR) fragments or proteins with a structure similar to TTR (accession numbers: PDB: 1GKO_A and 2PAB_A), retinol-binding protein 4 (RBP4) isoform X1 (no information in databases such as UNIPROT), and antibody fragments. Two proteins, APO-AIV and SP-40,40, were upregulated in group A than in O and C and in group I versus C, but not in group I versus O. Therefore, we suggest these proteins to be considered as candidates for the diagnosis of SLE.

摘要

系统性红斑狼疮(SLE)是一种自身免疫性结缔组织疾病,具有广泛的临床表现。免疫失调导致自身抗体和免疫复合物产生过多、补体激活和持续的组织炎症。鉴于目前的诊断依赖于美国风湿病学会制定的复杂标准的解释,且疾病过程的特点是不可预测的活动和缓解,每个患者表现出不同的症状,因此迫切需要发现特定的生物标志物。因此,本研究旨在确定潜在的用于区分活动性和非活动性 SLE 的生物标志物,这些生物标志物可能能够将实验室诊断的 SLE 与其他自身免疫性疾病区分开来。我们使用 2D-DIGE 蛋白质组学技术来评估活动性 SLE、非活动性 SLE、患有其他自身免疫性疾病的患者和健康个体之间蛋白质的差异丰度。与 C 和 O 组相比,有 6 种蛋白质在活动性 SLE(A)和非活动性 SLE(I)中表现出增加的丰度,但在 A 和 I 组之间没有差异。有两个转甲状腺素蛋白(TTR)片段或结构类似于 TTR 的蛋白质(PDB:1GKO_A 和 2PAB_A)、视黄醇结合蛋白 4(RBP4)X1 同工型(在 UNIPROT 等数据库中没有信息)和抗体片段。两种蛋白质,APO-AIV 和 SP-40,40,在 A 组中的表达高于 O 和 C 组,在 I 组中高于 C 组,但在 I 组中高于 O 组。因此,我们建议将这些蛋白质作为 SLE 诊断的候选标志物。

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