title: Protein species as diagnostic markers.
abstract: Many diseases are associated with protein species perturbations. A prominent example of an established diagnostic marker is the glycated protein species of hemoglobin, termed HbA1c. HbA1c concentration is increased in the blood of diabetes mellitus patients due to their poor control of blood glucose levels resulting in an increased non-enzymatic glycosylation of hemoglobin producing HbA1c. This important diagnostic marker is routinely measured in the blood of diabetes patients. As in the case of HbA1c, protein species can mirror pathophysiological events. Shifts in the levels of protein species can be associated with or even be responsible for disease making them well suited as diagnostic markers. However, only a few protein species are currently used as diagnostic markers in routine clinical chemistry laboratories, despite being widely established in clinical proteomics research. This review provides an overview of the biochemical characteristics associated with protein species as well as examples of pathophysiological mechanisms, which cause modifications in the protein species composition, thereby emphasizing the importance of screening for protein markers at the species level. Further, we highlight techniques, which are currently utilized for investigating protein species markers in clinical research.
  
  
  CONCLUSIONS
  The success rate of FDA approved diagnostic protein markers until today is very low compared to the number of published candidate disease markers. It is hypothesized that one important reason is the gene-centric view which is still followed in clinical proteomics: In many investigations proteins are still digested in small peptides thus making it nearly impossible to discriminate between healthy proteins and pathologic proteins causing diseases. Thus this review is focusing on the biochemistry and patho-biochemistry of proteins, is highlighting the need for screening for disease markers on the protein species level and is giving an overview about available techniques.
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Institute for Clinical Chemistry, Department for Mass Spectrometric Proteomics, Martinistraße 52, 20246 Hamburg, Germany. Electronic address: p.steffen@uke.de.
authors.forename: Pascal
authors.initials: P
authors.lastname: Steffen
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Institute for Clinical Chemistry, Department for Mass Spectrometric Proteomics, Martinistraße 52, 20246 Hamburg, Germany. Electronic address: m.kwiatkowksi@uke.de.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kwiatkowski
authors.affiliation: Max Planck Institute for the Structure and Dynamics of Matter, Atomically Resolved Dynamics Division, Luruper Chaussee 149, 22761, Hamburg, Germany. Electronic address: wesley.robertson@mpsd.mpg.de.
authors.forename: Wesley D
authors.initials: WD
authors.lastname: Robertson
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON M5G-1P5, Canada; Department of Medical Biophysics, University of Toronto, 101 College Street Suite 15-701, Toronto, ON M5G 1L7, Canada. Electronic address: arash.zarrine.afsar@utoronto.ca.
authors.forename: Arash
authors.initials: A
authors.lastname: Zarrine-Afsar
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Institute for Clinical Chemistry, Department for Mass Spectrometric Proteomics, Martinistraße 52, 20246 Hamburg, Germany. Electronic address: Diana.Deterra@gmx.de.
authors.forename: Diana
authors.initials: D
authors.lastname: Deterra
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Institute for Clinical Chemistry, Department for Mass Spectrometric Proteomics, Martinistraße 52, 20246 Hamburg, Germany. Electronic address: vrichter-bs@web.de.
authors.forename: Verena
authors.initials: V
authors.lastname: Richter
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Institute for Clinical Chemistry, Department for Mass Spectrometric Proteomics, Martinistraße 52, 20246 Hamburg, Germany. Electronic address: hschluet@uke.de.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schlüter
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood* / Q000175:diagnosis*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: Clinical chemistry; Mass spectrometry; Protein diagnostics; Protein species