Clinical Study of Microchimerism and cfDNA as Biomarkers for Acute Rejection After Organ Transplantation

NCT03255265 | Unknown

• 1 other identifier: cf-DNA
• Study Type: observational
• Target: 950
• Locations: 1 country
• Sites: 1

Brief Summary

Organ transplantation has become an effective therapy for patients with end-stage organ failure at present. Rejection is still the most common cause of early dysfunction after organ transplantation. A large number of experimental and clinical data are suggesting that the formation of microchimer can successfully achieve donor-specific immune tolerance after transplantation. The formation of microchimerism may be one of the long-term survival mechanisms of transplantation, and the detection of microchimerism after transplantation can effectively predict the rejection of grafts. Scientists from Stanford University in the United States continued to report in 2014 and 2015 that using a new generation of high-throughput sequencing technology (NGS) to detect the level of free DNA from donor in blood plasma of recipients after cardiac and lung transplantation. The investigators found the level of free DNA in donor significantly increased when acute or chronic rejection happens, thus it may be used as a reflection of rejection or graft injury markers. It has been reported that microchimerization and donor free DNA levels are associated with rejection after organ transplantation, but these studies are mostly based on a small number of cases and the results of which re qualitative and can not provide a specific microchimerization rate due to limited detection techniques. Therefore, in order to clarify the role of microchimerism and the level of cell-free DNA in donor in organ transplantation tolerance, it is necessary to use a new generation of detection technology for multi-center study with large samples. Clinical trial was used to evaluate the clinical prediction and diagnostic value of microchimerization rate and donor cfDNA for acute rejection after organ transplantation. 950 cases of organ transplantation, of which 600 cases of renal transplantation, 300 cases of liver transplantation and 50 cases of lung transplantation.8 ml peripheral blood was collected in 1 tubes with EDTA anticoagulation. The timing of the collection was as follows: Patients with routine treatment after transplantation were preformed once every one weeks for one months and then every 3 month until the one year. In case of acute rejection, the additional blood was collected once on the day of diagnosis, and once after the treatment remission. All the samples were detected for microchimerism and cfDNA.

Conditions

Organ Transplant Rejection

Keywords

organ transplantation; cfDNA; microchimerism; acute rejection

Outcome Measures

Primary Outcomes (1)

• Quantification of the donor microchimerism in recipients was conducted once a week for 1 month and then at 3, 6 and 12 months after transplantation.

  Around the 8mL peripheral whole blood was collected and the DNA in hemocytes was extracted for qPCR analysis. During which 30 target genomic genes were amplified, the donor microchimerism rate was quantified by former differentiating of InDel sites between the donor and the recipient.

  2017.4.1-2021.4.31

Secondary Outcomes (1)

• Quantification of the donor derived cfDNA rate in recipients was conducted once a week for 1 month and then at 3, 6 and 12 months after transplantation.

  2017.4.1-2021.4.31

Study Arms (2)

Acute rejection

Other: no interventions

No acute rejection

Other: no interventions

Interventions

no interventions OTHER

no interventions

Acute rejection; No acute rejection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

aged above 18 years old single organ transplant patients (first or again); Guardian or self-signed informed consent.

You may qualify if:

• Single-organ transplant recipients aged above 18 years old Recipients of re-do organ transplants
• Recipients with no systemic acute or chronic infections, infectious diseases;
• Recipients with no severe systemic diseases and/or spiritual system diseases
• Recipients or families signed the consent form.

You may not qualify if:

• Organ transplant recipients whose donor is child (under the age of 18 years old)
• Patients wait-listed for multiple organ transplantation
• Unable or unwilling to follow up regularly

Sponsors & Collaborators

• Fuzhou General Hospital: lead
• 309th Hospital of Chinese People's Liberation Army: collaborator
• Tianjin First Central Hospital: collaborator
• RenJi Hospital: collaborator
• Fudan University: collaborator
• Ruijin Hospital: collaborator
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator
• Huazhong University of Science and Technology: collaborator
• West China Hospital: collaborator
• Central South University: collaborator
• The Third Xiangya Hospital of Central South University: collaborator
• First Affiliated Hospital Xi'an Jiaotong University: collaborator
• Qianfoshan Hospital: collaborator
• Wuxi People's Hospital: collaborator
• Second Affiliated Hospital of Guangzhou Medical University: collaborator

Study Sites (1)

Fuzhou General Hospital, Xiamen Univ Fuzhou, Fujian China

Fuzhou, Fujian, 350025, China

RECRUITING

Related Publications (28)

• Adams KM, Nelson JL. Microchimerism: an investigative frontier in autoimmunity and transplantation. JAMA. 2004 Mar 3;291(9):1127-31. doi: 10.1001/jama.291.9.1127.

  PMID: 14996783 BACKGROUND

• Akamatsu Y, Ohkohchi N, Seya K, Satomi S. Analysis of bilirubin fraction in the bile for early diagnosis of acute rejection in living related liver transplantation. Tohoku J Exp Med. 1997 Jan;181(1):145-54. doi: 10.1620/tjem.181.145.

  PMID: 9149349 BACKGROUND

• Aljurf M, Abalkhail H, Alseraihy A, Mohamed SY, Ayas M, Alsharif F, Alzahrani H, Al-Jefri A, Aldawsari G, Al-Ahmari A, Belgaumi AF, Walter CU, El-Solh H, Rasheed W, Albitar M. Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies. Biotechnol Res Int. 2016;2016:8589270. doi: 10.1155/2016/8589270. Epub 2016 Feb 23.

  PMID: 27006832 BACKGROUND

• Ascher NL. Microchimerism in organ transplantation. Liver Transpl Surg. 1995 Jan;1(1):43-6. doi: 10.1002/lt.500010109. No abstract available.

  PMID: 9346540 BACKGROUND

• Avolio AW, Gozzo ML, Forni L, Agnes S, Colacicco L, Barbaresi G, Magalini SC, Castagneto M. Mitochondrial/cytoplasmic enzyme ratio for the diagnosis of acute rejection after liver transplantation: sensitivity and specificity. Transplant Proc. 1992 Dec;24(6):2572-3. No abstract available.

  PMID: 1361263 BACKGROUND

• Bakr MA, Nagib AM, Donia AF. Induction immunosuppressive therapy in kidney transplantation. Exp Clin Transplant. 2014 Mar;12 Suppl 1:60-9. doi: 10.6002/ect.25liver.l58.

  PMID: 24635795 BACKGROUND

• Bamgbola O. Metabolic consequences of modern immunosuppressive agents in solid organ transplantation. Ther Adv Endocrinol Metab. 2016 Jun;7(3):110-27. doi: 10.1177/2042018816641580. Epub 2016 Mar 30.

  PMID: 27293540 BACKGROUND

• Beck J, Oellerich M, Schulz U, Schauerte V, Reinhard L, Fuchs U, Knabbe C, Zittermann A, Olbricht C, Gummert JF, Shipkova M, Birschmann I, Wieland E, Schutz E. Donor-Derived Cell-Free DNA Is a Novel Universal Biomarker for Allograft Rejection in Solid Organ Transplantation. Transplant Proc. 2015 Oct;47(8):2400-3. doi: 10.1016/j.transproceed.2015.08.035.

  PMID: 26518940 BACKGROUND

• Biancofiore G, Pucci L, Cerutti E, Penno G, Pardini E, Esposito M, Bindi L, Pelati E, Romanelli A, Triscornia S, Salvadorini MP, Stratta C, Lanfranco G, Pellegrini G, Del Prato S, Salizzoni M, Mosca F, Filipponi F. Cystatin C as a marker of renal function immediately after liver transplantation. Liver Transpl. 2006 Feb;12(2):285-91. doi: 10.1002/lt.20657.

  PMID: 16447198 BACKGROUND

• Capron A, Haufroid V, Wallemacq P. Intra-cellular immunosuppressive drugs monitoring: A step forward towards better therapeutic efficacy after organ transplantation? Pharmacol Res. 2016 Sep;111:610-618. doi: 10.1016/j.phrs.2016.07.027. Epub 2016 Jul 25.

  PMID: 27468645 BACKGROUND

• Chen Y, Tai Q, Hong S, Kong Y, Shang Y, Liang W, Guo Z, He X. Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis. Transplantation. 2012 Nov 15;94(9):911-8. doi: 10.1097/TP.0b013e31826784ad.

  PMID: 23052636 BACKGROUND

• De Vlaminck I, Martin L, Kertesz M, Patel K, Kowarsky M, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Nicolls MR, Cornfield D, Weill D, Valantine H, Khush KK, Quake SR. Noninvasive monitoring of infection and rejection after lung transplantation. Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13336-41. doi: 10.1073/pnas.1517494112. Epub 2015 Oct 12.

  PMID: 26460048 BACKGROUND

• De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Bernstein D, Weisshaar D, Quake SR, Khush KK. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014 Jun 18;6(241):241ra77. doi: 10.1126/scitranslmed.3007803.

  PMID: 24944192 BACKGROUND

• Delville M, Charreau B, Rabant M, Legendre C, Anglicheau D. Pathogenesis of non-HLA antibodies in solid organ transplantation: Where do we stand? Hum Immunol. 2016 Nov;77(11):1055-1062. doi: 10.1016/j.humimm.2016.05.021. Epub 2016 May 26.

  PMID: 27237040 BACKGROUND

• Deschaseaux F, Delgado D, Pistoia V, Giuliani M, Morandi F, Durrbach A. HLA-G in organ transplantation: towards clinical applications. Cell Mol Life Sci. 2011 Feb;68(3):397-404. doi: 10.1007/s00018-010-0581-6. Epub 2010 Nov 20.

  PMID: 21103908 BACKGROUND

• Dragun D, Catar R, Philippe A. Non-HLA antibodies in solid organ transplantation: recent concepts and clinical relevance. Curr Opin Organ Transplant. 2013 Aug;18(4):430-5. doi: 10.1097/MOT.0b013e3283636e55.

  PMID: 23838648 BACKGROUND

• Dragun D, Hegner B. Non-HLA antibodies post-transplantation: clinical relevance and treatment in solid organ transplantation. Contrib Nephrol. 2009;162:129-39. doi: 10.1159/000170845. Epub 2008 Oct 31.

  PMID: 19001820 BACKGROUND

• Duan Z, Zhang Y, Pan F, Zhang T, Zeng Z, Wang S, Li G, Shen B, Gao J. Association between CTLA4 gene polymorphisms and acute rejection of kidney transplantation: a meta-analysis. J Nephrol. 2012 Nov-Dec;25(6):996-1002. doi: 10.5301/jn.5000082.

  PMID: 22307437 BACKGROUND

• Eigler J. [The acute rejection reaction following kidney transplantation. Diagnostic and therapeutic aspects]. Med Klin. 1978 Dec 1;73(48):1682-9. No abstract available. German.

  PMID: 364275 BACKGROUND

• Eikmans M, van Halteren AG, van Besien K, van Rood JJ, Drabbels JJ, Claas FH. Naturally acquired microchimerism: implications for transplantation outcome and novel methodologies for detection. Chimerism. 2014;5(2):24-39. doi: 10.4161/chim.28908.

  PMID: 24762743 BACKGROUND

• Elahimehr R, Scheinok AT, McKay DB. Hematopoietic stem cells and solid organ transplantation. Transplant Rev (Orlando). 2016 Oct;30(4):227-34. doi: 10.1016/j.trre.2016.07.005. Epub 2016 Aug 3.

  PMID: 27553809 BACKGROUND

• Espinel CH, Mendez-Picon G, Currier C, Novello A, Helfrich GB, Lee HM. FE Na effective in early diagnosis of acute rejection after kidney transplantation. Proc Clin Dial Transplant Forum. 1979;9:256-9. No abstract available.

  PMID: 399517 BACKGROUND

• Gambato M, Lens S, Fernandez-Carrillo C, Alfaro I, Forns X. Viral hepatitis and liver transplantation: pathogenesis, prevention and therapy of recurrent disease. Dig Dis. 2014;32(5):538-44. doi: 10.1159/000360831. Epub 2014 Jul 14.

  PMID: 25034286 BACKGROUND

• Garcia Moreira V, Prieto Garcia B, Baltar Martin JM, Ortega Suarez F, Alvarez FV. Cell-free DNA as a noninvasive acute rejection marker in renal transplantation. Clin Chem. 2009 Nov;55(11):1958-66. doi: 10.1373/clinchem.2009.129072. Epub 2009 Sep 3.

  PMID: 19729469 BACKGROUND

• Germani G, Rodriguez-Castro K, Russo FP, Senzolo M, Zanetto A, Ferrarese A, Burra P. Markers of acute rejection and graft acceptance in liver transplantation. World J Gastroenterol. 2015 Jan 28;21(4):1061-8. doi: 10.3748/wjg.v21.i4.1061.

  PMID: 25632178 BACKGROUND

• Gielis EM, Ledeganck KJ, De Winter BY, Del Favero J, Bosmans JL, Claas FH, Abramowicz D, Eikmans M. Cell-Free DNA: An Upcoming Biomarker in Transplantation. Am J Transplant. 2015 Oct;15(10):2541-51. doi: 10.1111/ajt.13387. Epub 2015 Jul 16.

  PMID: 26184824 BACKGROUND

• Gierej B, Kobryn K, Gierej P, Gornicka B. C4d in acute rejection after liver transplantation and its usefulness in differential diagnosis between acute liver rejection and hepatitis C recurrence. Ann Transplant. 2014 Aug 1;19:373-81. doi: 10.12659/AOT.890234.

  PMID: 25082343 BACKGROUND

• Gozzo ML, Avolio AW, Colacicco L, Agnes S, Forni F, Barbaresi G, Castagneto M. Mitochondrial liver enzymes and the ratio between mitochondrial and cytoplasmic enzymes in the differential diagnosis of acute rejection after liver transplantation. Transplant Proc. 1993 Apr;25(2):1760-1. No abstract available.

  PMID: 8097065 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

blood

Central Study Contacts

Jian ming Tan, Chief Physician

CONTACT

86-13375918000; tanjm156@xmu.edu.cn

Jun Lu, Chief Physician

CONTACT

86-13599091436; junlu.heather@xmu.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2017
• First Posted: August 21, 2017
• Study Start: March 1, 2017
• Primary Completion: September 28, 2021
• Study Completion: December 31, 2021
• Last Updated: August 21, 2017

Record last verified: 2017-04

Locations

CN (1)