title: Oncostatin M receptor β and cysteine/histidine-rich 1 are biomarkers of the response to erythropoietin in hemodialysis patients.
abstract: Biomarkers that evaluate the response to erythropoietic-stimulating agents largely measure inflammation and iron availability. While these are important factors in modifying an individual's response to these agents, they do not address all aspects of a poor response. To clarify this, we isolated peptides in the serum of good and poor responders to erythropoietin in order to identify biomarkers of stimulating agent response. Ninety-one candidate biomarker targets were identified and characterized using mass spectrometry, of which tandem mass spectroscopy provided partial amino-acid sequence information of 17 different peptides for 16 peptide masses whose abundance significantly differed between poor and good responders. The analysis concluded that three peptides associated with a poor response were derived from oncostatin M receptor β (OSMRβ). The 13 serum peptides associated with a good response were derived from fibrinogen α and β, coagulation factor XIII, complement C3, and cysteine/histidine rich 1(CYHR1). Poor response was most strongly associated with the OSMRβ fragment with the largest molecular weight, while a good response was most strongly associated with CYHR1. Immunoblots found the abundance of intact OSMRβ and CYHR1 significantly differed between good and poor responders. Thus, two measurable biomarkers of the response to erythropoietic-stimulating agents are present in the serum of treated patients.
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Merchant
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Gaweda
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky, USA.|The Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dailey
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Wilkey
authors.affiliation: Department of Medicine, Ohio State University School of Medicine, Columbus, Ohio, USA.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Ohio State University School of Medicine, Columbus, Ohio, USA.
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky, USA.|The Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky, USA.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Klein
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky, USA.|The Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Brier
mesh_terms: D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005345:Fibrinopeptide B / Q000032:analysis; D006801:Humans; D008297:Male; D053681:Oncostatin M Receptor beta Subunit / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D011506:Proteins / Q000032:analysis*; D006435:Renal Dialysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; C558786:CYHR1 protein, human; D016207:Cytokines; C508348:OSMR protein, human; D053681:Oncostatin M Receptor beta Subunit; D010446:Peptide Fragments; D011506:Proteins; D004921:Erythropoietin; D005345:Fibrinopeptide B