Proteomic patterns established with capillary electrophoresis and mass spectrometry for diagnostic purposes

Weissinger, Eva M.; Wittke, Stefan; Kaiser, Thorsten; Haller, Hermann; Bartel, Sebastian; Krebs, Ronald; Golovko, Igor; Rupprecht, Harald; Haubitz, Marion; Hecker, Hartmut; Mischak, Harald; Fliser, Danilo

doi:10.1111/j.1523-1755.2004.00659.x

Cited by 198 publications

(189 citation statements)

References 19 publications

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“…These patterns can be used for diagnostic purposes, since each renal disease produces a specific and typical urinary polypeptide pattern. The discrimination between different primary renal diseases was high with a sensitivity and specificity above 90% [41,54]. These results indicate that a "common biomarker", which should display unique characteristics (presence/absence or signal intensity) in each sample from patients with a defined kidney disease does not exist.…”

Section: Biomarker Discovery In Urinementioning

confidence: 77%

“…As evident from recent reports, this appears to be correct [12,41,[54][55][56], but a serious obstacle to this venture is the variability of polypeptides examined. Using CE-MS we documented that polypeptides in urine change significantly during the day, most likely as a consequence of physical activity, diet, smoking, etc.…”

Section: Biomarker Discovery In Urinementioning

confidence: 92%

“…To this end, we analyzed more than 100 samples from healthy subjects and identified a "normal" urine polypeptide pattern [12,40,41]. Moreover, using CE-MS together with the MosaiquesVisu software, we established characteristic polypeptide patterns for patients with various renal diseases, e.g., minimal-change disease, focalsegmental glomerulosclerosis, membranous glomerulonephritis, Immunoglobulin (IgA) nephropathy, and diabetic nephropathy [12,41,54,55]. These patterns can be used for diagnostic purposes, since each renal disease produces a specific and typical urinary polypeptide pattern.…”

Section: Biomarker Discovery In Urinementioning

confidence: 99%

“…Migration time and mass are used to assess the identity of a peptide. Since migration time varies depending on the ion load in the sample and signal intensity varies depending on the efficiency of ionization as well as the detector gain, the polypeptide list is normalized with respect to migration time and signal intensity in a consecutive step ( [41], see also Theodorescu et al, this issue).…”

Section: Software and Data Analysismentioning

confidence: 99%

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Capillary electrophoresis coupled to mass spectrometry for clinical diagnostic purposes

2005

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Capillary electrophoresis coupled to mass spectrometry for clinical diagnostic purposesThe introduction of fast, sensitive, and robust techniques for proteomic analysis into clinical practice represents a major step toward a new diagnostic approach of body fluids. In addition, proteomics emerges as a key technology for the discovery of disease biomarkers in various body fluids. However, even in relatively protein-deprived body fluids such as urine, the complexity and wide dynamic range of protein expression pose a considerable challenge to both separation and identification technologies. In the present review we discuss from a clinical point-of-view recent advances of the use of proteomics in clinical diagnosis as well as therapy evaluation. We focus on capillary electrophoresis coupled to mass spectrometry (CE-MS) and discuss CE-MS from an application point of view evaluating its merits and vices with regard to biomarker discovery. This review further presents examples of clinical applications of CE-MS for detection and identification of biomarkers in urine. IntroductionIt is well appreciated for centuries that body fluids contain information on the "internal" environment, i.e., the function of tissues and organs, which can be used as a gauge for the well being of the organism. Although this concept was created by Hippocrates more than 2000 years ago, standardized clinical laboratory tests were not developed before the 20th century. Moreover, a systematic discovery of biomarkers was made possible only with the discovery of antibodies and their use in immunological assays such as radioimmuno assay (RIA), ELISA, etc. Their increasing use enabled detection and quantification of distinct molecules -mainly peptides and proteins -in various body fluids. However, these techniques were limited by their requirement of prior knowledge of the molecule and a specific probe. New functional proteomic approaches appeared to circumvent these limitations. Spurred by advances in MS it was hoped that proteomics would allow the analysis of thousands of peptides and proteins in one sample [1][2][3][4][5][6], but several obstacles turned up soon. The high complexity and wide dynamic range of peptides in body fluids required pre-MS separation techniques that offer high resolution and could cope with a wide dynamic range of peptide concentrations [3]. Further, suitable software for interpretation of a vast number of generated MS spectra as well as comparison of the data was a major challenge [7].The approach towards solving most of these problems was to reduce data complexity, for example by arbitrarily collecting data on only a few polypeptides and also to reduce resolution of the analysis instrument. Both were accomplished with the surface-enhanced laser desorption/ionization (SELDI) technology -a complex solution of analytes was allowed to interact with an active surface (ion-exchange, hydro-

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Section: Biomarker Discovery In Urinementioning

confidence: 77%

Section: Biomarker Discovery In Urinementioning

confidence: 92%

Section: Biomarker Discovery In Urinementioning

confidence: 99%

Section: Software and Data Analysismentioning

confidence: 99%

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Capillary electrophoresis coupled to mass spectrometry for clinical diagnostic purposes

2005

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“…However, no single polypeptide was identified that would be characteristic for a specific disease and simultaneously absent in all control samples [207]. Urine of patients with kidney diseases provided 27 exclusive polypeptides and 13 others, present in control, were missing [122,212,215,216]. Similarly, CE-MS/MS was used to analyze urinary samples from 112 patients with type II diabetes.…”

Section: Urinary Proteinsmentioning

confidence: 99%

Capillary electrophoresis of proteins 2003–2005

Dolnı́k¹

2006

Electrophoresis

139

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This review article with 304 references describes recent developments in CE of proteins, and covers the two years since the previous review (Hutterer, K., Dolník, V., Electrophoresis 2003, 24, 3998-4012) through Spring 2005. It covers topics related to CE of proteins, including modeling of the electrophoretic migration of proteins, sample pretreatment, wall coatings, improving separation, various forms of detection, special electrophoretic techniques such as affinity CE, CIEF, and applications of CE to the analysis of proteins in real-world samples including human body fluids, food and agricultural samples, protein pharmaceuticals, and recombinant protein preparations.

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