4.6 Article

Comparison of Aptamer-Based and Antibody-Based Assays for Protein Quantification in Chronic Disease

Journal

Publisher

AMER SOC NEPHROLOGY
DOI: 10.2215/CJN.11700921

Keywords

AASK (African American Study of Kidney Disease and Hypertension); chronic kidney disease; end-stage renal disease; mortality; chronic inflammation; antibodies; biological assay

Funding

  1. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  2. National Institutes of Health (NIH)
  3. NIDDK [M01 RR-00080, M01 RR-00071, M0100032, P20-RR11145, M01 RR00827, M01 RR00052, 2P20 RR11104, RR029887, DK 2818-02, DK057867, DK048689]
  4. AstraZeneca
  5. Forest Laboratories
  6. GlaxoSmithKline
  7. King Pharmaceuticals
  8. Pfizer
  9. Pharmacia
  10. Upjohn

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This study evaluated the use of SOM Ascan technology for quantification of immune activation biomarkers and cystatin C in CKD. The results showed high correlations between SOM Ascan measurements and immunoassays. Certain biomarkers were associated with increased risks of kidney failure and all-cause mortality.
Background and objectives 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 SOM Ascan, 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 SOM Ascan 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. Results 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 (r=0.94, 0.93, 0.89, 0.85, 0.46, and 0.23, respectively) between SOM Ascan and immunoassay measurements, and three (IL-10, IFN-g, and TNF-a) were uncorrelated (r=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 via both methods. On average, immunoassay measurements were more strongly associated with adverse outcomes than their SOM Ascan counterparts. Conclusions SOM Ascan 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.

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