Skoglund C, Carlsen A L, Weiner M, Kurz T, Hellmark Thomas, Eriksson P, Heegaard N H H, Segelmark M
Department of Medical and Health Sciences, Linköping University, Sweden.
Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
Clin Exp Rheumatol. 2015 Mar-Apr;33(2 Suppl 89):S-64-71. Epub 2015 May 26.
Antineutrophil cytoplasmic antibody associated vasculitis (AAV) has an unpredictable course and better biomarkers are needed. Micro-RNAs in body fluids are protected from degradation and might be used as biomarkers for diagnosis and prognosis, here we explore the potential in AAV.
Plasma samples from two AAV cohorts (n=67 and 38) were compared with samples from healthy controls (n=27 and 45) and disease controls (n=20). A panel of 32 miRNAs was measured using a microfluidic quantitative real-time PCR system, and results were compared with clinical data.
Seven individual miRNAs were differently expressed compared to controls in both cohorts; miR-29a, -34a, -142-3p and -383 were up-regulated and miR-20a, -92a and -221 were down-regulated. Cluster analysis as well as principal component analysis (PCA) indicated that patterns of miRNA expression differentiate AAV patients from healthy subjects as well as from renal transplant recipients. Loadings plots indicated similar contribution of the same miRNAs in both cohorts to the PCA. Renal engagement was important for miRNA expression but consistent correlations between estimated glomerular filtration rate and miRNA levels were not found. We found no significant correlation between treatment regimens and circulating miRNA levels.
In this first study ever on circulating miRNA profiles in AAV, we find clear indication of their potential as biomarkers for diagnosis and classification, but more studies are needed to identify the best markers as well as the mechanisms responsible for variations.
抗中性粒细胞胞浆抗体相关性血管炎(AAV)病程不可预测,需要更好的生物标志物。体液中的微小RNA(miRNA)不易降解,可能用作诊断和预后的生物标志物,我们在此探索其在AAV中的潜力。
将两个AAV队列(n = 67和38)的血浆样本与健康对照(n = 27和45)及疾病对照(n = 20)的样本进行比较。使用微流控定量实时PCR系统检测一组32种miRNA,并将结果与临床数据进行比较。
在两个队列中,与对照组相比,有7种个体miRNA表达不同;miR-29a、-34a、-142-3p和-383上调,miR-20a、-92a和-221下调。聚类分析以及主成分分析(PCA)表明,miRNA表达模式可区分AAV患者与健康受试者以及肾移植受者。载荷图表明两个队列中相同的miRNA对PCA的贡献相似。肾脏受累对miRNA表达很重要,但未发现估计肾小球滤过率与miRNA水平之间存在一致的相关性。我们发现治疗方案与循环miRNA水平之间无显著相关性。
在这项关于AAV循环miRNA谱的首次研究中,我们明确表明它们有潜力作为诊断和分类的生物标志物,但需要更多研究来确定最佳标志物以及负责变异的机制。