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Elevated levels of ...
Elevated levels of circulating CDH5 and FABP1 in association with human drug-induced liver injury
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- Mikus, Maria (author)
- KTH,Proteomik och nanobioteknologi,KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Stockholm, Sweden.,Univ Malaga, Hosp Univ Virgen Victoria, IBIMA, UGC Gastroenterol & Hepatol & Serv Farmacol Clin, Malaga, Spain.
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- Drobin, Kimi (author)
- KTH,Proteomik och nanobioteknologi,KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Stockholm, Sweden.
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- Gry, Marcus (author)
- KTH,AstraZeneca R&D, Global Safety Assessment, Mol Toxicol, Södertälje, Sweden.
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- Bachmann, J. (author)
- KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Stockholm, Sweden.
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- Lindberg, J. (author)
- Karolinska Institutet,AstraZeneca R&D, Global Safety Assessment, Mol Toxicol, Södertälje, Sweden.
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- Yimer, G. (author)
- Univ Addis Ababa, Dept Pharmacol, Addis Ababa, Ethiopia.
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- Aklillu, E. (author)
- Karolinska Institutet,Karolinska Inst, Div Clin Pharmacol, Stockholm, Sweden.
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- Makonnen, E. (author)
- Univ Addis Ababa, Dept Pharmacol, Addis Ababa, Ethiopia.
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- Aderaye, G. (author)
- Univ Addis Ababa, Dept Internal Med, Addis Ababa, Ethiopia.
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- Roach, J. (author)
- Momenta Pharmaceut, Cambridge, MA USA.
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- Fier, I. (author)
- Momenta Pharmaceut, Cambridge, MA USA.
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- Kampf, Caroline (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Göpfert, J. (author)
- Univ Tubingen, Nat & Med Sci Inst, Dept Biochem, Reutlingen, Germany.
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- Perazzo, H. (author)
- Hop La Pitie Salpetriere, Hepatol Dept, Paris, France.
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- Poynard, T. (author)
- Hop La Pitie Salpetriere, Hepatol Dept, Paris, France.
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- Stephens, C. (author)
- Univ Malaga, Hosp Univ Virgen Victoria, IBIMA, UGC Gastroenterol & Hepatol & Serv Farmacol Clin, Malaga, Spain.
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- Andrade, R. J. (author)
- Univ Malaga, Hosp Univ Virgen Victoria, IBIMA, UGC Gastroenterol & Hepatol & Serv Farmacol Clin, Malaga, Spain.
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Lucena, M. I. (author)
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- Arber, N. (author)
- Tel Aviv Sourasky Med Ctr, Integrated Canc Prevent Ctr, Tel Aviv, Israel.
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- Uhlén, Mattias (author)
- KTH,Proteomik och nanobioteknologi,KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Stockholm, Sweden.
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- Watkins, P. B. (author)
- Univ North Carolina Chapel Hill, Sch Med, Chapel Hill, NC USA.
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- Schwenk, Jochen M (author)
- KTH,Proteomik och nanobioteknologi
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- Nilsson, Peter (author)
- KTH,Proteomik och nanobioteknologi,KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Stockholm, Sweden.
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- Schuppe-Koistinen, I. (author)
- Karolinska Institutet,Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;AstraZeneca R&D, Innovat Med Personalised Healthcare & Biomarkers, SciLifeLab, Stockholm, Sweden.
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(creator_code:org_t)
- 2016-06-22
- 2016
- English.
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In: Liver international. - : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 37:1, s. 132-140
- Related links:
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https://doi.org/10.1...
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https://onlinelibrar...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Background & Aims: The occurrence of drug-induced liver injury (DILI) is a major issue in all phases of drug development. To identify novel biomarker candidates associated with DILI, we utilised an affinity proteomics strategy, where antibody suspension bead arrays were applied to profile plasma and serum samples from human DILI cases and controls. Methods: An initial screening was performed using 4594 randomly selected antibodies, representing 3450 human proteins. Resulting candidate proteins together with proposed DILI biomarker candidates generated a DILI array of 251 proteins for subsequent target analysis and verifications. In total, 1196 samples from 241 individuals across four independent cohorts were profiled: healthy volunteers receiving acetaminophen, patients with human immunodeficiency virus and/or tuberculosis receiving treatment, DILI cases originating from a wide spectrum of drugs, and healthy volunteers receiving heparins. Results: We observed elevated levels of cadherin 5, type 2 (CDH5) and fatty acid-binding protein 1 (FABP1) in DILI cases. In the two longitudinal cohorts, CDH5 was elevated already at baseline. FABP1 was elevated after treatment initiation and seemed to respond more rapidly than alanine aminotransferase (ALT). The elevations were verified in the DILI cases treated with various drugs. In the heparin cohort, CDH5 was stable over time whereas FABP1 was elevated. Conclusions: These results suggest that CDH5 may have value as a susceptibility marker for DILI. FABP1 was identified as a biomarker candidate with superior characteristics regarding tissue distribution and kinetics compared to ALT but likely with limited predictive value for the development of severe DILI. Further studies are needed to determine the clinical utility of the proposed markers.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Keyword
- Affinity proteomics
- Biomarker discovery
- Drug-induced liver injury
- Plasma profiling
- Suspension bead arrays
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Mikus, Maria
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Drobin, Kimi
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Gry, Marcus
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Bachmann, J.
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Lindberg, J.
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Yimer, G.
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show more...
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Aklillu, E.
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Makonnen, E.
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Aderaye, G.
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Roach, J.
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Fier, I.
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Kampf, Caroline
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Göpfert, J.
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Perazzo, H.
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Poynard, T.
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Stephens, C.
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Andrade, R. J.
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Lucena, M. I.
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Arber, N.
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Uhlén, Mattias
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Watkins, P. B.
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Schwenk, Jochen ...
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Nilsson, Peter
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Schuppe-Koistine ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Gastroenterology ...
- Articles in the publication
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Liver internatio ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet
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Uppsala University