title: Proteomics applied to the clinical follow-up of patients after allogeneic hematopoietic stem cell transplantation.
abstract: A phase 1 diagnostic study was performed to evaluate a novel technology for clinical proteomic research based on capillary electrophoresis and mass spectrometry. Urine from 40 patients after hematopoietic stem cell transplantation (HSCT; 35 allogeneic, 5 autologous) and 5 patients with sepsis was collected for a period of 100 days and analyzed. More than 1000 different polypeptides could be detected in individual samples. Polypeptide patterns excreted in the urine of patients were significantly different from those of healthy volunteers. No significant differences were detected comparing different conditioning regimens. The aim of this study was to identify polypeptide patterns functioning as early indicators of graft-versus-host disease (GVHD). Eighteen patients developed GVHD after allogeneic HSCT. Sixteen differentially excreted polypeptides formed a pattern of early GVHD markers, allowing discrimination of GVHD from patients without complications with 82% specificity and 100% sensitivity, cross-validated. Inclusion of 13 sepsis-specific polypeptides allowed us to distinguish sepsis from GVHD with a specificity of 97% and a sensitivity of 100%. Sequencing 2 prominent GVHD-indicative polypeptides led to the identification of a peptide from leukotriene A4 hydrolase and a peptide from serum albumin. The data reveal that capillary electrophoresis and mass spectrometry allow identification of biomarkers for a variety of diseases or related complications.
authors.affiliation: Mosaiques Diagnostics and Therapeutics and Hannover Medical School, Hannover, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kaiser
authors.forename: Haytham
authors.initials: H
authors.lastname: Kamal
authors.forename: Andreas
authors.initials: A
authors.lastname: Rank
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Bernd
authors.initials: B
authors.lastname: Hertenstein
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Weissinger
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015415:Biomarkers; D019075:Electrophoresis, Capillary; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000652:urine*; D040901:Proteomics; D018805:Sepsis / Q000097:blood / Q000175:diagnosis*; D020539:Sequence Analysis, Protein; D014556:Urine
chemical_list: D015415:Biomarkers; D010455:Peptides