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Proteomic profiling of renal allograft rejection in serum using magnetic bead–based sample fractionation and MALDI-TOF MS

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Abstract

Proteomics is one of the emerging techniques for biomarker discovery. Biomarkers can be used for early noninvasive diagnosis and prognosis of diseases and treatment efficacy evaluation. In the present study, the well-established research systems of ClinProt Micro solution incorporated unique magnetic bead sample preparation technology, which, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), have become very successful in bioinformatics due to its outstanding performance and reproducibility for discovery disease-related biomarker. We collected fasting blood samples from patients with biopsy-confirmed acute renal allograft rejection (n = 12), chronic rejection (n = 12), stable graft function (n = 12) and also from healthy volunteers (n = 13) to study serum peptidome patterns. Specimens were purified with magnetic bead–based weak cation exchange chromatography and analyzed with a MALDI-TOF mass spectrometer. The results indicated that 18 differential peptide peaks were selected as potential biomarkers of acute renal allograft rejection, and 6 differential peptide peaks were selected as potential biomarkers of chronic rejection. A Quick Classifier Algorithm was used to set up the classification models for acute and chronic renal allograft rejection. The algorithm models recognize 82.64% of acute rejection and 98.96% of chronic rejection episodes, respectively. We were able to identify serum protein fingerprints in small sample sizes of recipients with renal allograft rejection and establish the models for diagnosis of renal allograft rejection. This preliminary study demonstrated that proteomics is an emerging tool for early diagnosis of renal allograft rejection and helps us to better understand the pathogenesis of disease process.

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References

  1. Cecka JM (2005) The OPTN/UNOS renal transplant registry. Clin Transpl 1–16 (PubMed: 17424721)

  2. Allen RDM, Chapman JR (1994) A manual of renal transplantation. Little Brown, Boston

    Google Scholar 

  3. Wilczek HE (1990) Percutaneous needle biopsy of the renal allograft. A clinical safety evaluation of 1129 biopsies. Transplantation 50(5):790–797 (PubMed:2238054)

    Article  PubMed  CAS  Google Scholar 

  4. Kolb LG, Velosa JA, Bergstralh EJ, Offord KP (1994) Percutaneous renal allograft biopsy. A comparison of two needle types and analysis of risk factors. Transplantation 57(12):1742–1745 (PubMed: 80168879)

    PubMed  CAS  Google Scholar 

  5. Roberti I, Reisman L (2001) Serial evaluation of cell surface markers for immune activation after acute renal allograft rejection by urine flow cytometry: correlation with clinical outcome. Transplantation 71(9):1317–1320 (PubMed: 11397970)

    Article  PubMed  CAS  Google Scholar 

  6. Woodle ES, Cronin D, Newell KA, Millis JM, Bruce DS, Piper JB et al (1996) Tacrolimus therapy for refractory acute renal allograft rejection: definition of the histologic response by protocol biopsies. Transplantation 62(7):906–910 (PubMed: 8878382)

    Article  PubMed  CAS  Google Scholar 

  7. Beckingham IJ, Nicholson ML, Bell PR (1994) Analysis of factors associated complications following renal transplant needle core biopsy. Br J Urol 73(1):13–15 (PubMed: 8298893)

    Article  PubMed  CAS  Google Scholar 

  8. Fiedler GM, Leichtle AB, Kase J, Baumann S, Ceglarek U, Felix K et al (2009) Serum peptidome profiling revealed platelet factor 4 as a potential discriminating Peptide associated with pancreatic cancer. Clin Cancer Res 15(11):3812–3819 (PubMed:19470732)

    Article  PubMed  CAS  Google Scholar 

  9. Schaub NP, Jones KJ, Nyalwidhe JO, Cazares LH, Karbassi ID, Semmes OJ et al (2009) Serum proteomic biomarker discovery reflective of stage and obesity in breast cancer patients. J Am Coll Surg 208(5):970–978 (PubMed:19476873)

    Article  PubMed  Google Scholar 

  10. Hinkelbein J, Feldmann RE Jr, Schubert C, Peterka A, Schelshorn D, Maurer MH et al (2009) Alterations in rat serum proteome and metabolome as putative disease markers in sepsis. J Trauma 66(4):1065–1075 (PubMed:19359916)

    Article  PubMed  CAS  Google Scholar 

  11. Pandey A, Mann M (2000) Proteomics to study genes and genomes. Nature 405(6788):837–846 (PubMed: 10866210)

    Article  PubMed  CAS  Google Scholar 

  12. Gilar M, Olivova P, Chakraborty AB, Jaworski A, Geromanos SJ, Gebler JC (2009) Comparison of 1-D and 2-D LC MS/MS methods for proteomic analysis of human serum. Electrophoresis 30(7):1157–1167 (PubMed:19283699)

    Article  PubMed  CAS  Google Scholar 

  13. Yu KH, Barry CG, Austin D, Busch CM, Sangar V, Rustgi AK et al (2009) Stable isotope dilution multidimensional liquid chromatography-tandem mass spectrometry for pancreatic cancer serum biomarker discovery. J Proteome Res 8(3):1565–1576 (PubMed:19199705)

    Article  PubMed  CAS  Google Scholar 

  14. Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M et al (2008) Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 8(4):753–760 (PubMed: 18294345)

    Article  PubMed  CAS  Google Scholar 

  15. Ketterlinus R, Hsieh SY, Teng SH, Lee H, Pusch W (2005) Fishing for biomarkers: analyzing mass spectrometry data with the new ClinPro Tools software. Biotechniques 38:37–40 (PubMed: 16528916)

    Article  Google Scholar 

  16. Kirk AD (2002) Location, location, location: regional immune mechanisms critically influence rejection. Nat Med 8(6):553–555 (PubMed: 12042797)

    Article  PubMed  CAS  Google Scholar 

  17. Qi F, Adair A, Ferenbach D, Vass DG, Mylonas KJ, Kipari T et al (2008) Depletion of cells of monocyte lineage prevents loss of renal microvasculature in murine kidney transplantation. Transplantation 86(9):1267–1274 (PubMed: 19005409)

    Article  PubMed  CAS  Google Scholar 

  18. Fu Y, Yi S, Wu J, Jimenez E, Simond D, Hawthorne WJ et al (2008) In vitro suppression of xenoimmune-mediated macrophage activation by human CD4+ CD25+ regulatory T cells. Transplantation 86(6):865–874 (PubMed:18813112)

    Article  PubMed  CAS  Google Scholar 

  19. Lin ML, Zhan Y, Nutt SL, Brady J, Wojtasiak M, Brooks AG et al (2006) NK cells promote peritoneal xenograft rejection through an IFN-gamma-dependent mechanism. Xenotransplantation 13(6):536–546 (PubMed: 17059581)

    Article  PubMed  Google Scholar 

  20. Amico P, Hönger G, Bielmann D, Lutz D, Garzoni D, Steiger J et al (2008) Incidence and prediction of early antibody-mediated rejection due to non-human leukocyte antigen-antibodies. Transplantation 85(11):1557–1563 (PubMed: 18551059)

    Article  PubMed  CAS  Google Scholar 

  21. Péfaur J, Díaz P, Panace R, Salinas P, Fiabane A, Quinteros N et al (2008) Early and late humoral rejection: a clinicopathologic entity in two times. Transplant Proc 40(9):3229–3236 (PubMed: 19010241)

    Article  PubMed  Google Scholar 

  22. Yang YW, Lin WC, Wu MS, Lee PH, Tsai MK (2008) Early diagnosis and successful treatment of acute antibody-mediated rejection of a renal transplant. Exp Clin Transplant 6(3):211–214 (PubMed: 18954299)

    PubMed  Google Scholar 

  23. Cruzado JM, Bestard O, Grinyó JM (2009) Control of anti-donor antibody production post-transplantation: conventional and novel immunosuppressive therapies. Contrib Nephrol 162:117–128 (PubMed: 19001819)

    Article  PubMed  CAS  Google Scholar 

  24. Lefaucheur C, Suberbielle-Boissel C, Hill GS, Nochy D, Andrade J, Antoine C et al (2009) Clinical relevance of preformed HLA donor-specific antibodies in kidney transplantation. Contrib Nephrol 162:1–12 (PubMed 09001809)

    Article  PubMed  CAS  Google Scholar 

  25. Elmagd MM, Bakr MA, Metwally AH, Wahab AM (2008) Clinicoepidemiologic study of posttransplant diabetes after living-donor renal transplant. Exp Clin Transplant 6(1):42–47 (PubMed: 18405244)

    PubMed  Google Scholar 

  26. Nwankwo EA, Bakari AA, Ene AC (2008) Post transplantation diabetes mellitus in kidney allograft recipients: Current concepts. Saudi J Kidney Dis Transpl 19(6):904–910 (PubMed: 18974574)

    PubMed  Google Scholar 

  27. Fernández-Fresnedo G, Gómez-Alamillo C, Ruiz JC, de Francisco AL, Arias M (2009) Chronic renal disease in renal transplant patients: management of cardiovascular risk factors. Transplant Proc 41(5):1637–1638 (PubMed:19545697)

    Article  PubMed  Google Scholar 

  28. Paoletti E, Gherzi M, Amidone M, Massarino F, Cannella G (2009) Association of arterial hypertension with renal target organ damage in kidney transplant recipients: the predictive role of ambulatory blood pressure monitoring. Transplantation 87(12):1864–1869 (PubMed 19543066)

    Article  PubMed  Google Scholar 

  29. Díaz Gómez JM (2008) Cardiovascular mortality in kidney transplantation. Nefrologia 28(5):27–30 (PubMed: 18847417)

    PubMed  Google Scholar 

  30. Aalten J, Hoogeveen EK, Roodnat JI, Weimar W, Borm GF, de Fijter JW et al (2008) Associations between pre-kidney-transplant risk factors and post-transplant cardiovascular events and death. Transpl Int 21(10):985–991 (PubMed: 18564985)

    Article  PubMed  Google Scholar 

  31. Sharifipour F, Rezaeetalab F, Naghibi M (2009) Pulmonary fungal infections in kidney transplant recipients: an 8-year study. Transplant Proc 41(5):1654–1656 (PubMed:19545701)

    Article  PubMed  CAS  Google Scholar 

  32. Linares L, Cervera C, Cofán F, Lizaso D, Marco F, Ricart MJ et al (2008) Risk factors for infection with extended-spectrum and AmpC beta-lactamase-producing gram-negative rods in renal transplantation. Am J Transplant 8(5):1000–1005 (PubMed: 18727176)

    Article  PubMed  CAS  Google Scholar 

  33. Khameneh ZR (2008) Occurrence of cytomegalovirus infection and factors causing reactivation of the infection among renal transplant recipients: a single center study. Saudi J Kidney Dis Transpl 19(1):41–45 (PubMed: 18087121)

    PubMed  Google Scholar 

  34. Végso G, Járay J (2007) Malignant tumors following renal transplantation. Orv Hetil 148(45):2115–2123 (PubMed: 17984022)

    Article  PubMed  Google Scholar 

  35. Donia AF, Mostafa A, Refaie H, El-Baz M, Kamal MM, Ghoneim MA (2008) Postkidney transplant malignancy in Egypt has a unique pattern: a three-decade experience. Transplantation 86(8):1139–1142 (PubMed: 18946354)

    Article  PubMed  Google Scholar 

  36. Falsarella PM, Alves-Filho G, Mazzali M (2008) Skin malignancies in renal transplant recipients: a Brazilian center registry. Transplant Proc 40(3):767–768 (PubMed: 18455011)

    Article  PubMed  CAS  Google Scholar 

  37. Huang Z, Shi Y, Cai B, Wang L, Wu Y, Ying B et al (2009) MALDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers and establishment of boosting decision tree model for diagnosis of systemic lupus erythematosus. Rheumatology (Oxford) 48(6):626–631 (PubMed:19389822)

    Article  CAS  Google Scholar 

  38. Alagaratnam S, Mertens BJ, Dalebout JC, Deelder AM, van Ommen GJ, den Dunnen JT et al (2008) Serum protein profiling in mice: identification of Factor XIIIa as a potential biomarker for muscular dystrophy. Proteomics 8(8):1552–1563 (PubMed: 18409166)

    Article  PubMed  CAS  Google Scholar 

  39. Navare A, Zhou M, McDonald J, Noriega FG, Sullards MC, Fernandez FM (2008) Serum biomarker profiling by solid-phase extraction with particle-embedded micro tips and matrix-assisted laser desorption/ionization mass spectrometry. Rapid Commun Mass Spectrom 22(7):997–1008 (PubMed: 18320548)

    Article  PubMed  CAS  Google Scholar 

  40. Kobayashi CA, Leite AL, Silva TL, Santos LD, Nogueira FC, Oliveira RC et al (2009) Proteomic analysis of kidney in rats chronically exposed to fluoride. Chem Biol Interact 180(2):305–311 (PubMed:19497429)

    Article  PubMed  CAS  Google Scholar 

  41. Dai Y, Lv T, Wang K, Huang Y, Li D, Liu J (2008) Detection of acute renal allograft rejection by analysis of renal tissue proteomics in rat models of renal transplantation. Saudi J Kidney Dis Transpl 19(6):952–959 (PubMed: 18974583)

    PubMed  Google Scholar 

  42. Wannemacher KM, Terskiy A, Bian S, Yadav PN, Li H, Howells RD (2008) Purification and mass spectrometric analysis of the kappa opioid receptor. Brain Res 1230:13–26 (PubMed: 18656460)

    Article  PubMed  CAS  Google Scholar 

  43. Yu M, Wang X, Du Y, Chen H, Guo X, Xia L et al (2008) Comparative analysis of renal protein expression in spontaneously hypertensive rat. Clin Exp Hypertens 30(5):315–325 (PubMed: 18633755)

    Article  PubMed  CAS  Google Scholar 

  44. O’Riordan E, Orlova TN, Mei JJ, Butt K, Chander PM, Rahman S et al (2004) Bioinformatic analysis of the urine proteome of acute allograft rejection. J Am Soc Nephrol 15(12):3240–3248 (PubMed: 15579528)

    Article  PubMed  Google Scholar 

  45. Quintana LF, Solé-Gonzalez A, Kalko SG, Bañon-Maneus E, Solé M, Diekmann F et al (2009) Urine proteomics to detect biomarkers for chronic allograft dysfunction. J Am Soc Nephrol 20(2):428–435 (PubMed: 19056874)

    Article  PubMed  CAS  Google Scholar 

  46. Wang JN, Zhou Y, Zhu TY, Wang X, Guo YL (2008) Prediction of acute cellular renal allograft rejection by urinary metabolomics using MALDI-FTMS. J Proteome Res 7(8):3597–3601 (PubMed: 18620448)

    Article  PubMed  CAS  Google Scholar 

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No financial relationship exists between any of the authors and any commercial interest with a vested interest in the outcome of the study.

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Authors and Affiliations

  1. First Kidney Transplantation and Hemopurification Center of Chinese PLA, 181st Hospital of Guangzhou Military Area of PLA, 541002, Guilin, Guangxi Province, People’s Republic of China

    Weiguo Sui, Liling Huang, Jiejing Chen, Qiang Yan & He Huang

  2. Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), 518020, Shenzhen, Guangdong Province, People’s Republic of China

    Yong Dai

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  1. Weiguo Sui
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  2. Liling Huang
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  3. Yong Dai
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  4. Jiejing Chen
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Correspondence to Yong Dai.

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Sui, W., Huang, L., Dai, Y. et al. Proteomic profiling of renal allograft rejection in serum using magnetic bead–based sample fractionation and MALDI-TOF MS. Clin Exp Med 10, 259–268 (2010). https://doi.org/10.1007/s10238-010-0094-5

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  • DOI: https://doi.org/10.1007/s10238-010-0094-5

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