Background Inflammatory arthritis (IA) is an immunological disorder in which loss of immune tolerance to endogenous self-antigens perpetuates synovitis and eventual destruction of the underlying cartilage and bone. Pathological changes in the joint are expected to be represented by synovial fluid (SF) proteins and peptides. In the present study, a mass spectrometry-based approach was utilized for the identification of key protein and peptide mediators of IA. Methods Age-matched SF samples from 10 rheumatoid arthritis patients, 10 psoriatic arthritis patients and 10 cadaveric controls were subjected to an integrated proteomic and peptidomic protocol using liquid chromatography tandem mass spectrometry. Significant differentially abundant proteins and peptides were identified between cohorts according to the results of a Mann-Whitney U test coupled to the Benjamini-Hochberg correction for multiple hypothesis testing. Fold change ratios were computed for each protein and peptide according to their log-transformed extracted ion current. Pathway analysis and antimicrobial peptide (AMP) prediction were conducted to clarify the pathophysiological relevance of identified proteins and peptides to IA. Results We determined that 144 proteins showed significant differential abundance between the IA and control SF proteomes, of which 11 protein candidates were selected for future follow-up studies. Similar analyses applied to our peptidomic data identified 15 peptide sequences, originating from 4 protein precursors, to have significant differential abundance in IA compared to the control SF peptidome. Pathway enrichment analysis of the IA SF peptidome along with AMP prediction suggests a possible mechanistic role of microbes in eliciting an immune response which drives the development of IA. Conclusions The discovery-phase data generated herein has provided a basis for the identification of candidates with the greatest potential to serve as novel serum biomarkers specific to inflammatory arthritides. Moreover, these findings facilitate the understanding of possible disease mechanisms specific to each subtype.

中文翻译：

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使用无标记质谱法阐明炎症性关节炎的内源性滑液蛋白质组和肽组。

背景炎性关节炎 (IA) 是一种免疫疾病，其中对内源性自身抗原的免疫耐受性丧失导致滑膜炎持续存在并最终破坏潜在的软骨和骨骼。预计关节中的病理变化以滑液 (SF) 蛋白质和肽为代表。在本研究中，基于质谱的方法用于鉴定 IA 的关键蛋白质和肽介质。方法 使用液相色谱串联质谱法对来自 10 名类风湿性关节炎患者、10 名银屑病关节炎患者和 10 名尸体对照的年龄匹配的 SF 样本进行综合蛋白质组学和肽组学方案。根据 Mann-Whitney U 检验与多假设检验的 Benjamini-Hochberg 校正相结合的结果，在群组之间鉴定出显着差异丰富的蛋白质和肽。根据对数转换的提取离子电流计算每种蛋白质和肽的倍数变化率。进行了通路分析和抗菌肽 (AMP) 预测，以阐明鉴定的蛋白质和肽与 IA 的病理生理相关性。结果 我们确定 144 种蛋白质在 IA 和对照 SF 蛋白质组之间显示出显着的差异丰度，其中选择了 11 种候选蛋白质用于未来的后续研究。应用于我们的肽组数据的类似分析确定了 15 个肽序列，源自 4 个蛋白质前体，与对照 SF 肽组相比，在 IA 中具有显着的差异丰度。IA SF 肽组的通路富集分析以及 AMP 预测表明微生物在引发免疫反应中可能发挥作用，从而推动 IA 的发展。结论 本文产生的发现阶段数据为鉴定最有可能用作炎症性关节炎特异性新血清生物标志物的候选物提供了基础。此外，这些发现有助于理解每种亚型特有的可能疾病机制。结论 本文产生的发现阶段数据为鉴定最有可能用作炎症性关节炎特异性新血清生物标志物的候选物提供了基础。此外，这些发现有助于理解每种亚型特有的可能疾病机制。结论 本文产生的发现阶段数据为鉴定最有可能用作炎症性关节炎特异性新血清生物标志物的候选物提供了基础。此外，这些发现有助于理解每种亚型特有的可能疾病机制。