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

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  • Artificial Kidney / Dialysis
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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.

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References

  1. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Williams SC. After Xigris, researchers look to new targets to combat sepsis. Nat Med. 2012;18:1001.

    Article  CAS  PubMed  Google Scholar 

  3. Vincent JL, Opal SM, Marshall JC, Tracey KJ. Sepsis definitions: time for change. Lancet. 2013;381:774–5.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Matsuda K, Hirasawa H, Oda S, Shiga H, Nakanishi K. Current topics on cytokine removal technologies. Ther Apher. 2001;5:306–14.

    Article  CAS  PubMed  Google Scholar 

  5. Nakada TA, Hirasawa H, Oda S, Shiga H, Matsuda K. Blood purification for hypercytokinemia. Transfus Apher Sci. 2006;35:253–64.

    Article  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. Cao Z, Robinson RA. The role of proteomics in understanding biological mechanisms of sepsis. Proteom Clin Appl. 2014;8:35–52.

    Article  CAS  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. Tolwani A. Continuous renal-replacement therapy for acute kidney injury. N Engl J Med. 2012;367:2505–14.

    Article  CAS  PubMed  Google Scholar 

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med. 2004;351:159–69.

    Article  CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. 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  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  CAS  PubMed  Google Scholar 

  25. 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.

    CAS  PubMed  Google Scholar 

  26. 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.

    Article  CAS  PubMed  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nelson A, Berkestedt I, Bodelsson M. Circulating glycosaminoglycan species in septic shock. Acta Anaesthesiol Scand. 2014;58:36–43.

    Article  CAS  PubMed  Google Scholar 

  31. Vantaku VR, Gupta G, Rapalli KC, Karnati R. Lacritin Salvages human corneal epithelial cells from lipopolysaccharide induced cell death. Sci Rep. 2015;5:18362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by Yoshimi Memorial T.M.P. Grant. We thank Fumie Iida for her technical expertise. Dr. Nakada and Hashida are inventors in a patent application filed and maintained by Chiba University related to this work.

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Correspondence to Taka-aki Nakada.

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Hashida, T., Nakada, Ta., Satoh, M. et al. Proteome analysis of hemofilter adsorbates to identify novel substances of sepsis: a pilot study. J Artif Organs 20, 132–137 (2017). https://doi.org/10.1007/s10047-016-0936-3

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  • DOI: https://doi.org/10.1007/s10047-016-0936-3

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