Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Clin J Am Soc Nephrol. 2022 Mar;17(3):350-360. doi: 10.2215/CJN.11700921. Epub 2022 Feb 23.
Novel aptamer-based technologies can identify >7000 analytes per sample, offering a high-throughput alternative to traditional immunoassays in biomarker discovery. However, the specificity for distinct proteins has not been thoroughly studied in the context of CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We assessed the use of SOMAscan, an aptamer-based technology, for the quantification of eight immune activation biomarkers and cystatin C among 498 African American Study of Kidney Disease and Hypertension (AASK) participants using immunoassays as the gold standard. We evaluated correlations of serum proteins as measured by SOMAscan versus immunoassays with each other and with iothalamate-measured GFR. We then compared associations between proteins measurement with risks of incident kidney failure and all-cause mortality.
Six biomarkers (IL-8, soluble TNF receptor superfamily member 1B [TNFRSF1B], cystatin C, soluble TNF receptor superfamily member 1A [TNFRSF1A], IL-6, and soluble urokinase-type plasminogen activator receptor [suPAR]) had non-negligible correlations (=0.94, 0.93, 0.89, 0.85, 0.46, and 0.23, respectively) between SOMAscan and immunoassay measurements, and three (IL-10, IFN-, and TNF-) were uncorrelated (=0.08, 0.07, and 0.02, respectively). Of the six biomarkers with non-negligible correlations, TNFRSF1B, cystatin C, TNFRSF1A, and suPAR were negatively correlated with measured GFR and associated with higher risk of kidney failure. IL-8, TNFRSF1B, cystatin C, TNFRSF1A, and suPAR were associated with a higher risk of mortality both methods. On average, immunoassay measurements were more strongly associated with adverse outcomes than their SOMAscan counterparts.
SOMAscan is an efficient and relatively reliable technique for quantifying IL-8, TNFRSF1B, cystatin C, and TNFRSF1A in CKD and detecting their potential associations with clinical outcomes.
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_23_CJN11700921.mp3.
新型适配子技术可在单次样本中鉴定 >7000 种分析物,为生物标志物发现提供了一种高通量替代传统免疫测定的方法。然而,在慢性肾脏病(CKD)背景下,其针对不同蛋白质的特异性尚未得到充分研究。
设计、地点、参与者和测量方法:我们评估了 SOMAscan(一种适配子技术)在 498 名非裔美国人肾脏病和高血压研究(AASK)参与者中的使用情况,使用免疫测定作为金标准来定量 8 种免疫激活生物标志物和胱抑素 C。我们评估了 SOMAscan 与免疫测定之间血清蛋白测量值的相关性,以及与碘海醇测量的肾小球滤过率(GFR)之间的相关性。然后,我们比较了蛋白质测量值与新发肾脏衰竭和全因死亡率风险之间的关联。
六种生物标志物(IL-8、可溶性肿瘤坏死因子受体超家族成员 1B [TNFRSF1B]、胱抑素 C、可溶性肿瘤坏死因子受体超家族成员 1A [TNFRSF1A]、IL-6 和可溶性尿激酶型纤溶酶原激活物受体 [suPAR])在 SOMAscan 与免疫测定测量值之间具有显著相关性(分别为=0.94、0.93、0.89、0.85、0.46 和 0.23),而三种生物标志物(IL-10、IFN-γ和 TNF-α)无相关性(分别为=0.08、0.07 和 0.02)。在具有显著相关性的六种生物标志物中,TNFRSF1B、胱抑素 C、TNFRSF1A 和 suPAR 与测量的 GFR 呈负相关,并与肾脏衰竭风险增加相关。IL-8、TNFRSF1B、胱抑素 C、TNFRSF1A 和 suPAR 与死亡率均呈正相关(两种方法均如此)。平均而言,免疫测定测量值与不良结局的相关性强于 SOMAscan 测量值。
SOMAscan 是一种高效且相对可靠的技术,可用于定量 CKD 中的 IL-8、TNFRSF1B、胱抑素 C 和 TNFRSF1A,并检测它们与临床结局的潜在关联。