Jin Yanyan, He Xue, Lin Weiqiang, Peng Zhaoyang, Li Wei, Xiang Wenqing, Chen Zhihui, Fu Haidong, Mao Jianhua
Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Biomol Biomed. 2025 Apr 26;25(6):1425-1443. doi: 10.17305/bb.2024.11081.
This study aimed to discover novel serum biomarkers for IgA vasculitis with nephritis (IgAVN). The serum of IgA vasculitis (IgAV) patients without nephritis and IgAVN patients not treated with glucocorticoids was analyzed for 440 proteins using a novel quantitative planar protein microarray. To verify the biomarkers, semiquantitative immunofluorescence analysis was performed on selected differential cytokines in a separate cohort of kidney tissue samples. A total of 41 proteins were differentially expressed between the IgAVN and IgAV groups out of the 440 proteins analyzed. Five differentially abundant proteins, including VEGF R3, ADAM12, TIM-3, IL-12p40, and CEACAM-5, were further validated by semiquantitative immunofluorescence analysis in kidney tissue from independent cohorts. ADAM12, TIM-3, IL-12p40, and CEACAM-5 were expressed in kidney tissue. A linear relationship was observed between the pathological grade of IgAVN and the expression levels of ADAM12 and CEACAM-5. Furthermore, while the prognosis of children with IgAVN may have a linear relationship with CEACAM-5, the results did not indicate a significant statistical difference, which may be related to the sample size. The expression of ADAM12 and CEACAM-5 were positively correlated with the pathological grade. More importantly, we found that CEACAM-5 may be related to the prognosis of IgAVN, which could serve as a significant biomarker for assessing disease severity and monitoring disease progression.
本研究旨在发现用于IgA血管炎伴肾炎(IgAVN)的新型血清生物标志物。使用新型定量平面蛋白质微阵列对未患肾炎的IgA血管炎(IgAV)患者以及未接受糖皮质激素治疗的IgAVN患者的血清进行了440种蛋白质分析。为了验证这些生物标志物,在另一组肾脏组织样本中对选定的差异细胞因子进行了半定量免疫荧光分析。在所分析的440种蛋白质中,共有41种蛋白质在IgAVN组和IgAV组之间差异表达。通过在独立队列的肾脏组织中进行半定量免疫荧光分析,进一步验证了5种差异丰富的蛋白质,包括血管内皮生长因子受体3(VEGF R3)、解聚素金属蛋白酶12(ADAM12)、T细胞免疫球蛋白黏蛋白分子3(TIM-3)、白细胞介素12 p40(IL-12p40)和癌胚抗原相关细胞黏附分子5(CEACAM-5)。ADAM12、TIM-3、IL-12p40和CEACAM-5在肾脏组织中表达。观察到IgAVN的病理分级与ADAM12和CEACAM-5的表达水平之间存在线性关系。此外,虽然IgAVN患儿的预后可能与CEACAM-5存在线性关系,但结果未显示出显著的统计学差异,这可能与样本量有关。ADAM12和CEACAM-5的表达与病理分级呈正相关。更重要的是,我们发现CEACAM-5可能与IgAVN的预后相关,它可作为评估疾病严重程度和监测疾病进展的重要生物标志物。