Serum Protein Signatures Using Aptamer-Based Proteomics for Minimal Change Disease and Membranous Nephropathy

Aptamer-Based Proteomic Platform for Human Immune-Mediated Kidney Diseases

“…Use of proteomics approaches, such as laser microdissection followed by tandem mass spectrometry, has also led to the discovery of additional proteins as target antigens of MN, including exostosin 1/exostosin 2, neural epidermal growth factor-like 1, semaphorin-3B, and protocadherin 7. 4 In this issue, Muruve et al 5 used quantitative SOMAscan and aptamer-based proteomics to identify serum protein biomarkers of MCD and MN (Figure 1). By analyzing serum samples from patients with biopsy-confirmed MCD and MN and healthy control participants using SOMAscan (SomaLogic, Boulder, CO), the authors identified 208 and 244 proteins that differentiated MCD and MN from healthy controls, respectively, among the 1305 proteins detected.…”

“…In addition, hierarchical clustering and the second unsupervised learning method spotlighted a set of proteins that allowed excellent discrimination of patients with MCD from those with MN and healthy controls and could discriminate patients with MN from those with MCD or healthy controls. 5 Aptamers are short, 20 to 80 nucleotides, single-stranded DNA or RNA sequences (nucleic acid Correspondence: Hiroshi Nishi, Division of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: hrnishi-tky@ umin.ac.jp aptamers) or proteins (peptide aptamers) that bind to target molecules, such as proteins, cells, metal ions, and even small organic molecules, with high affinity and specificity.…”

“…This increased capability is the major advantage of SOMAscan over conventional measures, in addition to its high sensitivity (median lower limit of detention of 40 fM), high reproducibility (median coefficient of variance <5%), and dynamic ranges. 5 However, there exists scope for improvement considering the specificity of this approach. 7,8 It should be noted that the binding affinity of aptamers to proteins may be influenced by numerous molecular properties, such as protein structure, posttranslational modifications, genetic polymorphisms, and complex formation.…”

“…To mechanistically extend the results obtained using SOMAscan, Muruve et al 5 further explored the underlying signaling pathways in MCD and MN. The highly discriminatory proteins in the MCD signature had a prominent increase in immune and growth factor signaling proteins and in carbohydrate and lipid metabolism.…”

“…Although dyslipidemia is a wellknown manifestation of nephrotic syndrome, it is intriguing that dysregulation of fatty acid metabolism pathways has been documented in both MN and MCD. 5 Both immune-mediated kidney diseases may be associated with the facilitation of liver lipid metabolism secondary to hypoalbuminemia and injury to the kidney tubular cells. In addition, their pathway analysis nicely provides a novel hypothesis regarding the underlying pathophysiology; although, it is yet to be applied as a precise target in clinical settings.…”