title: Proteomics Approach Identifies Factors Associated With the Response to Low-Density Lipoprotein Apheresis Therapy in Patients With Steroid-Resistant Nephrotic Syndrome.
abstract: Low-density lipoprotein apheresis (LDL-A) has been shown to reduce proteinuria in a subgroup of nephrotic syndrome patients refractory to immunosuppressive therapy. Factors influencing the efficacy of LDL-A in nephrotic syndrome are completely unknown. Using a proteomics approach, we aimed to identify biological markers that predict the response to LDL-A in patients with steroid-resistant nephrotic syndrome (SRNS). Identification of plasma proteins bound to the dextran-sulfate column at the first session of LDL-A was determined by mass spectrometry. To investigate biological factors associated with the response to LDL-A, we compared profiles of column-bound proteins between responders (defined by more than 50% reduction of proteinuria after the treatment) and non-responders by 2-dimensional gel electrophoresis (2-DE) coupled to mass spectrometry in seven patients with SRNS. Evaluation of proteins adsorbed to LDL-A column in patients with SRNS revealed the identity of 62 proteins, which included apolipoproteins, complement components, and serum amyloid P-component (SAP). Comparative analysis of the column-bound proteins between responders and non-responders by 2-DE demonstrated that apolipoprotein E (APOE) and SAP levels were increased in non-responders as compared with responders. These results were confirmed by western blotting. Moreover, serum levels of APOE and SAP were significantly higher in the non-responder group than in the responder group by ELISA. Our data provide comprehensive analysis of proteins adsorbed by LDL-A in SRNS, and demonstrate that the serum levels of APOE and SAP may be used to predict the response to LDL-A in these patients.
authors.affiliation: Departments of Internal Medicine.
authors.forename: Emiko
authors.initials: E
authors.lastname: Kuribayashi-Okuma
authors.affiliation: Departments of Internal Medicine.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Departments of Internal Medicine.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Arai
authors.affiliation: Departments of Internal Medicine.
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Ota
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo.
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Biochemistry, Teikyo University School of Medicine, Itabashi-ku.
authors.forename: Harumi
authors.initials: H
authors.lastname: Hisaki
authors.affiliation: Biochemistry, Teikyo University School of Medicine, Itabashi-ku.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Okazaki
authors.affiliation: Advanced Medical Research Center, Yokohama City University, Kanazawa-ku, Yokohama, Kanagawa, Japan.
authors.forename: Tosifusa
authors.initials: T
authors.lastname: Toda
authors.affiliation: Departments of Internal Medicine.
authors.forename: Shunya
authors.initials: S
authors.lastname: Uchida
mesh_terms: D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000097:blood; D001781:Blood Component Removal / Q000379:methods*; D001798:Blood Proteins / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood*; D016264:Dextran Sulfate / Q000737:chemistry; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000628:therapy*; D040901:Proteomics / Q000379:methods*; D000683:Serum Amyloid P-Component / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D001798:Blood Proteins; D008078:Cholesterol, LDL; D005938:Glucocorticoids; D000683:Serum Amyloid P-Component; D016264:Dextran Sulfate
keywords: Apolipoprotein E; Low-density lipoprotein apheresis; Proteomics; Serum amyloid P-component; Steroid-resistant nephrotic syndrome