School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
J Proteomics. 2022 Jan 16;251:104399. doi: 10.1016/j.jprot.2021.104399. Epub 2021 Oct 27.
SAPHO syndrome is an inflammatory disease invading the skin and bones, whose diagnosis has been difficult due to its low incidence and diversified manifestation. We investigated the serum proteomic profile of SAPHO patients to identify key proteins associated with SAPHO syndrome, trying to find clinical biomarkers or functional molecules for this rare disease. Blood samples from 8 SAPHO patients and 8 healthy controls were detected and analyzed using data independent acquisition (DIA) method to identify differentially expressed proteins (DEPs) specific to SAPHO. A total of 57 differentially expressed proteins were identified (p < 0.05, fold change >1.2), in which 27 proteins were upregulated and 30 downregulated. DEPs may participate in GO terms such as "lipid particle" and "Notch signaling pathway", as well as KEGG pathways including "complement and coagulation cascades" and "mTOR signaling pathway". The overexpression of inhibitors of the complement system (CFH and C4BP), were verified in a larger cohort (16 SAPHO patients, 8 AS patients and 24 healthy controls) with ELISA, and the combined diagnostic ability of CFH and C4BP was predicted by ROC curve with an AUC of 0.91, which may be molecular candidates for further study on diagnosis and pathology of this rare disease. SIGNIFICANCE: Our research provided the first insight into plasma proteomic profile for SAPHO patients，offering potential biomarkers for disease diagnosis. We found that inhibitors of complement system such as CFH and C4BP were up-regulated in SAPHO syndrome, which may play important roles in the pathogenesis of SAPHO syndrome.
SAPHO 综合征是一种侵犯皮肤和骨骼的炎症性疾病，由于其发病率低且表现多样化，诊断一直具有挑战性。我们研究了 SAPHO 患者的血清蛋白质组谱，以鉴定与 SAPHO 综合征相关的关键蛋白质，试图为这种罕见疾病找到临床生物标志物或功能分子。使用数据非依赖性采集（DIA）方法检测和分析 8 例 SAPHO 患者和 8 例健康对照者的血液样本，以鉴定 SAPHO 特有的差异表达蛋白（DEPs）。共鉴定出 57 个差异表达蛋白（p<0.05，倍数变化>1.2），其中 27 个蛋白上调，30 个蛋白下调。DEPs 可能参与 GO 术语，如“脂质颗粒”和“Notch 信号通路”，以及包括“补体和凝血级联”和“mTOR 信号通路”在内的 KEGG 途径。通过 ELISA 在更大的队列（16 例 SAPHO 患者、8 例 AS 患者和 24 例健康对照者）中验证了补体系统抑制剂（CFH 和 C4BP）的过表达，通过 ROC 曲线预测 CFH 和 C4BP 的联合诊断能力，AUC 为 0.91，它们可能是进一步研究这种罕见疾病的诊断和发病机制的分子候选物。意义：我们的研究首次提供了 SAPHO 患者血浆蛋白质组谱的见解，为疾病诊断提供了潜在的生物标志物。我们发现 SAPHO 综合征中补体系统抑制剂如 CFH 和 C4BP 上调，它们可能在 SAPHO 综合征的发病机制中发挥重要作用。
