Skip to main content
Erschienen in: Journal of Artificial Organs 2/2017

17.11.2016 | Original Article

Proteome analysis of hemofilter adsorbates to identify novel substances of sepsis: a pilot study

verfasst von: Tomoaki Hashida, Taka-aki Nakada, Mamoru Satoh, Keisuke Tomita, Rui Kawaguchi, Fumio Nomura, Shigeto Oda

Erschienen in: Journal of Artificial Organs | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

Abstract

Blood purification therapy using hemofilters with high adsorbing capabilities has been reported to remove excessive humoral mediators from the blood of patients with sepsis. However, there are insufficient studies of the adsorbates bound to hemofilter membranes. We hypothesized that these adsorbates in acute kidney injury (AKI) patients with sepsis were different from those in patients without sepsis and that proteome analysis of the adsorbates would identify novel substances of sepsis. This study included 20 patients who had AKI upon admission to intensive care units (ICUs) and who received continuous renal replacement therapy using polymethyl methacrylate hemofilters. We isolated adsorbates from the hemofilters after use and performed comprehensive proteome analysis. A total of 429 proteins were identified in these adsorbates. Adsorbates from the hemofilters of patients with sepsis had significantly increased frequency of proteins associated with “immune system process” and “biological adhesion” functions compared to those of non-sepsis patients (P < 0.05). Of 429 proteins, 197 were identified only in sepsis adsorbates. Of these, 3 proteins including carbonic anhydrase 1 (CA1) and leucine-rich alpha-2-glycoprotein (LRG1) were identified in all samples from sepsis patients and have not been previously reported in sepsis patients. Validation analysis of patient serum revealed that patients with sepsis had increased serum levels of CA1 and LRG1 compared to patients without sepsis (P < 0.05). To conclude, there were significant differences in the characteristics of the adsorbates from sepsis and non-sepsis patients. CA1 and LRG1 appear to be novel substances associated with sepsis.
Literatur
1.
Zurück zum Zitat Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–10.CrossRefPubMedPubMedCentral Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–10.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Williams SC. After Xigris, researchers look to new targets to combat sepsis. Nat Med. 2012;18:1001.CrossRefPubMed Williams SC. After Xigris, researchers look to new targets to combat sepsis. Nat Med. 2012;18:1001.CrossRefPubMed
4.
Zurück zum Zitat Matsuda K, Hirasawa H, Oda S, Shiga H, Nakanishi K. Current topics on cytokine removal technologies. Ther Apher. 2001;5:306–14.CrossRefPubMed Matsuda K, Hirasawa H, Oda S, Shiga H, Nakanishi K. Current topics on cytokine removal technologies. Ther Apher. 2001;5:306–14.CrossRefPubMed
5.
Zurück zum Zitat Nakada TA, Hirasawa H, Oda S, Shiga H, Matsuda K. Blood purification for hypercytokinemia. Transfus Apher Sci. 2006;35:253–64.CrossRefPubMed Nakada TA, Hirasawa H, Oda S, Shiga H, Matsuda K. Blood purification for hypercytokinemia. Transfus Apher Sci. 2006;35:253–64.CrossRefPubMed
6.
Zurück zum Zitat Hirayama Y, Oda S, Wakabayashi K, Sadahiro T, Nakamura M, Watanabe E, et al. Comparison of interleukin-6 removal properties among hemofilters consisting of varying membrane materials and surface areas: an in vitro study. Blood Purif. 2011;31:18–25.CrossRefPubMed Hirayama Y, Oda S, Wakabayashi K, Sadahiro T, Nakamura M, Watanabe E, et al. Comparison of interleukin-6 removal properties among hemofilters consisting of varying membrane materials and surface areas: an in vitro study. Blood Purif. 2011;31:18–25.CrossRefPubMed
7.
Zurück zum Zitat Hirasawa H, Oda S, Nakamura M, Watanabe E, Shiga H, Matsuda K. Continuous hemodiafiltration with a cytokine-adsorbing hemofilter for sepsis. Blood Purif. 2012;34:164–70.CrossRefPubMed Hirasawa H, Oda S, Nakamura M, Watanabe E, Shiga H, Matsuda K. Continuous hemodiafiltration with a cytokine-adsorbing hemofilter for sepsis. Blood Purif. 2012;34:164–70.CrossRefPubMed
8.
Zurück zum Zitat Legrand M, Darmon M, Joannidis M, Payen D. Management of renal replacement therapy in ICU patients: an international survey. Intensive Care Med. 2013;39:101–8.CrossRefPubMed Legrand M, Darmon M, Joannidis M, Payen D. Management of renal replacement therapy in ICU patients: an international survey. Intensive Care Med. 2013;39:101–8.CrossRefPubMed
9.
Zurück zum Zitat Cao Z, Robinson RA. The role of proteomics in understanding biological mechanisms of sepsis. Proteom Clin Appl. 2014;8:35–52.CrossRef Cao Z, Robinson RA. The role of proteomics in understanding biological mechanisms of sepsis. Proteom Clin Appl. 2014;8:35–52.CrossRef
10.
Zurück zum Zitat Hattori N, Oda S, Sadahiro T, Nakamura M, Abe R, Shinozaki K, et al. YKL-40 identified by proteomic analysis as a biomarker of sepsis. Shock. 2009;32:393–400.CrossRefPubMed Hattori N, Oda S, Sadahiro T, Nakamura M, Abe R, Shinozaki K, et al. YKL-40 identified by proteomic analysis as a biomarker of sepsis. Shock. 2009;32:393–400.CrossRefPubMed
11.
Zurück zum Zitat Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644–55.CrossRefPubMed Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644–55.CrossRefPubMed
12.
Zurück zum Zitat Satoh M, Haruta-Satoh E, Omori A, Oh-Ishi M, Kodera Y, Furudate S, et al. Effect of thyroxine on abnormal pancreatic proteomes of the hypothyroid rdw rat. Proteomics. 2005;5:1113–24.CrossRefPubMed Satoh M, Haruta-Satoh E, Omori A, Oh-Ishi M, Kodera Y, Furudate S, et al. Effect of thyroxine on abnormal pancreatic proteomes of the hypothyroid rdw rat. Proteomics. 2005;5:1113–24.CrossRefPubMed
13.
Zurück zum Zitat Rappsilber J, Mann M, Ishihama Y. Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat Protoc. 2007;2:1896–906.CrossRefPubMed Rappsilber J, Mann M, Ishihama Y. Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat Protoc. 2007;2:1896–906.CrossRefPubMed
14.
Zurück zum Zitat Okajima K, Harada N. Regulation of inflammatory responses by sensory neurons: molecular mechanism(s) and possible therapeutic applications. Curr Med Chem. 2006;13:2241–51.CrossRefPubMed Okajima K, Harada N. Regulation of inflammatory responses by sensory neurons: molecular mechanism(s) and possible therapeutic applications. Curr Med Chem. 2006;13:2241–51.CrossRefPubMed
15.
Zurück zum Zitat Cummings CJ, Sessler CN, Beall LD, Fisher BJ, Best AM, Fowler AA 3rd. Soluble E-selectin levels in sepsis and critical illness. Correlation with infection and hemodynamic dysfunction. Am J Respir Crit Care Med. 1997;156:431–7.CrossRefPubMed Cummings CJ, Sessler CN, Beall LD, Fisher BJ, Best AM, Fowler AA 3rd. Soluble E-selectin levels in sepsis and critical illness. Correlation with infection and hemodynamic dysfunction. Am J Respir Crit Care Med. 1997;156:431–7.CrossRefPubMed
16.
Zurück zum Zitat Tolwani A. Continuous renal-replacement therapy for acute kidney injury. N Engl J Med. 2012;367:2505–14.CrossRefPubMed Tolwani A. Continuous renal-replacement therapy for acute kidney injury. N Engl J Med. 2012;367:2505–14.CrossRefPubMed
17.
Zurück zum Zitat Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–8.CrossRefPubMed Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–8.CrossRefPubMed
18.
19.
Zurück zum Zitat Kalenka A, Feldmann RE Jr, Otero K, Maurer MH, Waschke KF, Fiedler F. Changes in the serum proteome of patients with sepsis and septic shock. Anesth Analg. 2006;103:1522–6.CrossRefPubMed Kalenka A, Feldmann RE Jr, Otero K, Maurer MH, Waschke KF, Fiedler F. Changes in the serum proteome of patients with sepsis and septic shock. Anesth Analg. 2006;103:1522–6.CrossRefPubMed
20.
Zurück zum Zitat Ando T, Iizuka N, Sato T, Chikada M, Kurokawa MS, Arito M, et al. Autoantigenicity of carbonic anhydrase 1 in patients with abdominal aortic aneurysm, revealed by proteomic surveillance. Hum Immunol. 2013;74:852–7.CrossRefPubMed Ando T, Iizuka N, Sato T, Chikada M, Kurokawa MS, Arito M, et al. Autoantigenicity of carbonic anhydrase 1 in patients with abdominal aortic aneurysm, revealed by proteomic surveillance. Hum Immunol. 2013;74:852–7.CrossRefPubMed
21.
Zurück zum Zitat Yagi S, Abe M, Yamashita M, Mori K, Yamanishi H, Arimitsu E, et al. Carbonic anhydrate I epitope peptide improves inflammation in a murine model of inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:1835–46.CrossRefPubMed Yagi S, Abe M, Yamashita M, Mori K, Yamanishi H, Arimitsu E, et al. Carbonic anhydrate I epitope peptide improves inflammation in a murine model of inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:1835–46.CrossRefPubMed
22.
Zurück zum Zitat O’Donnell LC, Druhan LJ, Avalos BR. Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation. J Leukoc Biol. 2002;72:478–85.PubMed O’Donnell LC, Druhan LJ, Avalos BR. Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation. J Leukoc Biol. 2002;72:478–85.PubMed
23.
Zurück zum Zitat Serada S, Fujimoto M, Ogata A, Terabe F, Hirano T, Iijima H, et al. iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases. Ann Rheum Dis. 2010;69:770–4.CrossRefPubMed Serada S, Fujimoto M, Ogata A, Terabe F, Hirano T, Iijima H, et al. iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases. Ann Rheum Dis. 2010;69:770–4.CrossRefPubMed
24.
Zurück zum Zitat Wang X, Abraham S, McKenzie JA, Jeffs N, Swire M, Tripathi VB, et al. LRG1 promotes angiogenesis by modulating endothelial TGF-beta signalling. Nature. 2013;499:306–11.CrossRefPubMed Wang X, Abraham S, McKenzie JA, Jeffs N, Swire M, Tripathi VB, et al. LRG1 promotes angiogenesis by modulating endothelial TGF-beta signalling. Nature. 2013;499:306–11.CrossRefPubMed
25.
Zurück zum Zitat Moore E, Bellomo R, Nichol A. Biomarkers of acute kidney injury in anesthesia, intensive care and major surgery: from the bench to clinical research to clinical practice. Minerva Anestesiol. 2010;76:425–40.PubMed Moore E, Bellomo R, Nichol A. Biomarkers of acute kidney injury in anesthesia, intensive care and major surgery: from the bench to clinical research to clinical practice. Minerva Anestesiol. 2010;76:425–40.PubMed
26.
Zurück zum Zitat Sprong T, Roos D, Weemaes C, Neeleman C, Geesing CL, Mollnes TE, et al. Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with meningococcal infections. Blood. 2006;107:4865–70.CrossRefPubMed Sprong T, Roos D, Weemaes C, Neeleman C, Geesing CL, Mollnes TE, et al. Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with meningococcal infections. Blood. 2006;107:4865–70.CrossRefPubMed
27.
Zurück zum Zitat Fernandez-Celemin L, Thissen JP. Interleukin-6 stimulates hepatic insulin-like growth factor binding protein-4 messenger ribonucleic acid and protein. Endocrinology. 2001;142:241–8.CrossRefPubMed Fernandez-Celemin L, Thissen JP. Interleukin-6 stimulates hepatic insulin-like growth factor binding protein-4 messenger ribonucleic acid and protein. Endocrinology. 2001;142:241–8.CrossRefPubMed
28.
Zurück zum Zitat Jennewein C, Tran N, Paulus P, Ellinghaus P, Eble JA, Zacharowski K. Novel aspects of fibrin(ogen) fragments during inflammation. Mol Med. 2011;17:568–73.CrossRefPubMedPubMedCentral Jennewein C, Tran N, Paulus P, Ellinghaus P, Eble JA, Zacharowski K. Novel aspects of fibrin(ogen) fragments during inflammation. Mol Med. 2011;17:568–73.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Chen Y, Han H, Yan X, Ding F, Su X, Wang H, et al. Tetranectin as a potential biomarker for stable coronary artery disease. Sci Rep. 2015;5:17632.CrossRefPubMedPubMedCentral Chen Y, Han H, Yan X, Ding F, Su X, Wang H, et al. Tetranectin as a potential biomarker for stable coronary artery disease. Sci Rep. 2015;5:17632.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Nelson A, Berkestedt I, Bodelsson M. Circulating glycosaminoglycan species in septic shock. Acta Anaesthesiol Scand. 2014;58:36–43.CrossRefPubMed Nelson A, Berkestedt I, Bodelsson M. Circulating glycosaminoglycan species in septic shock. Acta Anaesthesiol Scand. 2014;58:36–43.CrossRefPubMed
31.
Zurück zum Zitat Vantaku VR, Gupta G, Rapalli KC, Karnati R. Lacritin Salvages human corneal epithelial cells from lipopolysaccharide induced cell death. Sci Rep. 2015;5:18362.CrossRefPubMedPubMedCentral Vantaku VR, Gupta G, Rapalli KC, Karnati R. Lacritin Salvages human corneal epithelial cells from lipopolysaccharide induced cell death. Sci Rep. 2015;5:18362.CrossRefPubMedPubMedCentral
Metadaten
Titel
Proteome analysis of hemofilter adsorbates to identify novel substances of sepsis: a pilot study
verfasst von
Tomoaki Hashida
Taka-aki Nakada
Mamoru Satoh
Keisuke Tomita
Rui Kawaguchi
Fumio Nomura
Shigeto Oda
Publikationsdatum
17.11.2016
Verlag
Springer Japan
Erschienen in
Journal of Artificial Organs / Ausgabe 2/2017
Print ISSN: 1434-7229
Elektronische ISSN: 1619-0904
DOI
https://doi.org/10.1007/s10047-016-0936-3

Weitere Artikel der Ausgabe 2/2017

Journal of Artificial Organs 2/2017 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

CME: 2 Punkte

Prof. Dr. med. Gregor Antoniadis Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

CME: 2 Punkte

Dr. med. Benjamin Meyknecht, PD Dr. med. Oliver Pieske Das Webinar S2e-Leitlinie „Distale Radiusfraktur“ beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

CME: 2 Punkte

Dr. med. Mihailo Andric
Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.