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TOLERANCE WITHOUT MICROCHIMERISM: IS THAT POSSIBLE IN LIVER TRANSPLANTATION?

Year 2021, Volume: 28 Issue: 3, 403 - 410, 13.09.2021
https://doi.org/10.17343/sdutfd.811187

Abstract

Objective
It is uncovered the relationship between microchimerism
and liver graft tolerance. Many studies inspired the
concept of microchimerism and tolerance in solid
organ transplantation (SOT). Our aim is to explore this
aspect in a strictly selected patients’ cohort on CD3+
cells to show the microhimerism disappearance prove
the tolerance instead of presence of it.
Materials and Methods
We strictly selected liver transplantation patients
treated with calcineurins inhibitors (cnis), with
very low dose of drugs who has never developed
documented rejection. The DNA extraction and
microchimerism research method used was based
on the discrimination of donor and recipient alleles
by PCR amplification of microsatellite markers and
capillary electrophoresis with fluorescence detection.
Results
Twelve patients with alcohol-induced cirrhosis
without rejection or rejection-related complications
during the post-operative course were selected. The
immunosuppressive regimen included tacrolimus and
mycophenolate mofetil. The blood residual tacrolimus
concentration was under or equal 5 ng/L below normal.
We described the count of white blood cells and
selected CD3+ after the MACS separation procedure.
In our study, we did not observe any microchimerism
in none of the patients.
Discussion
We achieved that in case of absence of microchimerism
with maintained biochemical stability we could choose
to switch off the immunosuppressive therapy even
the microchimerism accepted like a condition to the
tolerance till our study. Consequently, it will be reduce
the side effects of immunosuppressive treatment
such as renal failure, metabolic disorders, diabetes
mellitus and cancers and the patient's quality of life
will be improved be decreased financial aspect of
immunesuppressive treathment

References

  • 1. Manzia TM, Angelico R, Gazia C, Lenci I, Milana M, Ademoyero OT.De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature.World J Gastroenterol. 2019 Sep 21;25(35):5356-5375.
  • 2. Stolp J, Zaitsu M, and Kathryn J. Wood Immune Tolerance and Rejection in Organ Transplantation. Methods Mol Biol. 2019;1899:159-180.
  • 3. Wang P, Jiang Z, Wang C, Liu X, Li H, Xu D.Immune Tolerance Induction Using Cell-Based Strategies in Liver Transplantation: Clinical Perspectives. Front Immunol. 2020 Aug 18;11:1723.
  • 4. Mazariegos G.V, Immunosuppression Withdrawal After Liver Transplantation: What Are the Next Steps? Transplantation, 2011. 91: p. 697-699.
  • 5. Hotta K, Aoyama A, Oura T, Yamada Y, Tonsho M, Huh KH. Induced Regulatory T Cells in Allograft Tolerance via Transient Mixed Chimerism JCI Insight . 2016 Jul 7;1(10):e86419.
  • 6. Feng S, Bucuvalas J. Tolerance After Liver Transplantation: Where Are We? Liver Transpl. 2017 Dec;23(12):1601-1614.
  • 7. Zhang CX, Wen PH, Sun YL. Withdrawal of immunosuppression in liver transplantation and the mechanism of tolerance Hepatobiliary Pancreat Dis Int. 2015 Oct;14(5):470-6.
  • 8. Minnie M Sarwal Review Clin Biochem.. Fingerprints of Transplant Tolerance Suggest Opportunities for Immunosuppression Minimization 2016 Mar;49(4-5):404-10
  • 9. Thomas E. Starzl, A.J.D., Noriko Murase, Massimo Trucco, Angus W.Thomson, Abdul S. Rao, and John J. Fung, Chimerism after organ transplantation. Curr Opin Nephrol Hypertens, 1997. 6(3): p. 292–298.
  • 10. Starzl TE , A.J.D., Trucco M, Murase N, Ricordi C, Ildstad S, Ramos H.Cell Migration and Chimerism After Whole-organ Transplantation:The Basis of Graft Acceptance. Hepatoloy, 1993. 17(6): p. 1127–1152.
  • 11. Starzl TE, A.J.D, Trucco M, Zeevi A, Ramos H, Terasaki P.Chimerism and Donor-specific non reactivity 27 to 29 years after kidney allotransplantation. Transplantation, 1993. 55(6): p. 1272–1277.
  • 12. Stephen I, Alexander, M.B., B.., Neil Smith, M.B., B.S., Min Hu, M.D., M.Med., et al, Chimerism and Tolerance in a Recipient of a Deceased-Donor Liver Transplant. NEJM, 2008. 358: p. 369-74.
  • 13. Mazariegos GV. Marino IR, Demetris AJ, Flynn B, Irish W, Michael JM, John J. Weaning of immunosuppression in liver transplant recipients. Transplantation, 1997. 27(63): p. 243-249.
  • 14 . Tryphonopoulos, P.Weppler D, Nishida S, Levi DM, Moon J, Tekin A. Madeline Velez, Danielle Rachel Neuman, Eddie Island, Gennaro Selvaggi, and Andreas G. Tzakis, Long-Term Follow-Up of 23 Operational Tolerant LiverTransplant Recipients. Transplantation, 2010. 90: p. 1556-1561.
  • 15. Tryphonopoulos P, Ruiz P, Weppler D, Nishida S, Levi DM, Moon J. Long-term follow-up of 23 operational tolerant liver transplant recipients. Transplantation. 2010 Dec 27;90(12):1556-61.
  • 16. Jain A, Mazariegos G, Pokharna R, Parizhskaya M, Kashyap R, Kosmach-Park B. The Absence of Chronic Rejection in Pediatric Primary Liver Transplant Patients Who Are Maintained on Tacrolimus-Based Immunosuppression: A Long-Term Analysis Transplantation. 2003 Apr 15;75(7):1020-5.
  • 17. Pilat N, W.T, Transplantation tolerance through mixed chimerism. Nat Rev Nephrol, 2010. 6(10): p. 594-605.
  • 18. Kinsella FAM, Zuo J, Inman CF, Pearce H, Maggs L, Eldershaw SE.Mixed chimerism established by hematopoietic stem cell transplantation is maintained by host and donor T regulatory cells. Blood Adv. 2019 Mar 12;3(5):734-743.
  • 19. Rickert CG, Markmann JF. Current state of organ transplant tolerance. Curr Opin Organ Transplant. 2019 Aug;24(4):441-450.
  • 20. Bishop GA, P., Bertolino PD, David G. Bowen, Geoffrey W. McCaughan. Tolerance in liver transplantation. Best Practice & Research Clinical Gastroenterology, 2012. 26: p. 73-84.
  • 21. Szabolcs P, W.J.B,. Thomson AV, Tolerance after solid organ and hematopoietic cell transplantation. Biol Blood Marrow Transplant, 2012. 18: p. 193-200.
  • 22. Harmon C, Sanchez-Fueyo A, O'Farrelly C, Houlihan DD. Natural Killer Cells and Liver Transplantation: Orchestrators of Rejection or Tolerance? Am J Transplant. 2016 Mar;16(3):751-7.
  • 23. Abrol N, Jadlowiec CC, Taner T. Revisiting the liver's role in transplant alloimmunity. World J Gastroenterol. 2019 Jul 7;25(25):3123-3135.

KARACİĞER TRANSPLANTASYONUNDA MİKROKİMERİZM OLMADAN TOLERANS MÜMKÜN MÜDÜR?

Year 2021, Volume: 28 Issue: 3, 403 - 410, 13.09.2021
https://doi.org/10.17343/sdutfd.811187

Abstract

Amaç
Karaciğer transplantasyonu sonrası tolerans kavramı
son yıllarda giderek popülarite kazanmaktadır. Bu çalışmada
amacımız çok özenli parametrelerle seçilmiş
yaklaşık on yıllık bir seride düşük doz immünosupressif
kullanan bir grupta toleransın varlığını CD3+
hücrelerde mikrokimerizmin yokluğu ile kanıtlamaya
çalışmaktır.
Gereç ve Yöntem
Mikrokimerizm yokluğunu araştırma yöntemi; retrospektif
olarak donör kanlarından cross match yapılarak
DNA izolasyonunun ardından, mikrosatellit markerlarının
PCR ile amplifikasyonu ve dönör ve alıcı allellerinin
karşılaştırılması ilkesine dayanıyordu.
Bulgular
Postoperatif takiplerinde organ reddi ya da buna bağlı
komplikasyonları olmayan alkole bağlı sirozu olan
12 hastadan bir izogrup oluşturuldu. Bu hastalar immunsüpresif
olarak takrolimus ve mikofenolat mofetil
kullanıyordu ve ilaç kan düzeyleri 5 ng/l yani kabul
edilebilir sınırın altında idi. Çalışmamızda hiçbir hastamızda
kimerizm gözlemlemedik.
Sonuç
Biyokimyasal stabiliteyi koruyan mikrokimerizmin
yokluğu yani transplantasyona tolerans olması durumunda
immunsupressif tedavilerin kesilebilir olmasının
düşünülebilirliği gündeme gelmektedir.Böylelikle
immünsüpressif tedavilerin yan etkileri azalacak ve
hastalar böbrek yetmezliği, metabolik bozukluklar,
diyabet ve kanserlerin artmış riskinden korunacak,
dolayısı ile yaşam kalitesi artmış ve transplantasyon
sonrası kullanılan ilaçların ülke ekonomisine yükü
azalmış olacaktır.

References

  • 1. Manzia TM, Angelico R, Gazia C, Lenci I, Milana M, Ademoyero OT.De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature.World J Gastroenterol. 2019 Sep 21;25(35):5356-5375.
  • 2. Stolp J, Zaitsu M, and Kathryn J. Wood Immune Tolerance and Rejection in Organ Transplantation. Methods Mol Biol. 2019;1899:159-180.
  • 3. Wang P, Jiang Z, Wang C, Liu X, Li H, Xu D.Immune Tolerance Induction Using Cell-Based Strategies in Liver Transplantation: Clinical Perspectives. Front Immunol. 2020 Aug 18;11:1723.
  • 4. Mazariegos G.V, Immunosuppression Withdrawal After Liver Transplantation: What Are the Next Steps? Transplantation, 2011. 91: p. 697-699.
  • 5. Hotta K, Aoyama A, Oura T, Yamada Y, Tonsho M, Huh KH. Induced Regulatory T Cells in Allograft Tolerance via Transient Mixed Chimerism JCI Insight . 2016 Jul 7;1(10):e86419.
  • 6. Feng S, Bucuvalas J. Tolerance After Liver Transplantation: Where Are We? Liver Transpl. 2017 Dec;23(12):1601-1614.
  • 7. Zhang CX, Wen PH, Sun YL. Withdrawal of immunosuppression in liver transplantation and the mechanism of tolerance Hepatobiliary Pancreat Dis Int. 2015 Oct;14(5):470-6.
  • 8. Minnie M Sarwal Review Clin Biochem.. Fingerprints of Transplant Tolerance Suggest Opportunities for Immunosuppression Minimization 2016 Mar;49(4-5):404-10
  • 9. Thomas E. Starzl, A.J.D., Noriko Murase, Massimo Trucco, Angus W.Thomson, Abdul S. Rao, and John J. Fung, Chimerism after organ transplantation. Curr Opin Nephrol Hypertens, 1997. 6(3): p. 292–298.
  • 10. Starzl TE , A.J.D., Trucco M, Murase N, Ricordi C, Ildstad S, Ramos H.Cell Migration and Chimerism After Whole-organ Transplantation:The Basis of Graft Acceptance. Hepatoloy, 1993. 17(6): p. 1127–1152.
  • 11. Starzl TE, A.J.D, Trucco M, Zeevi A, Ramos H, Terasaki P.Chimerism and Donor-specific non reactivity 27 to 29 years after kidney allotransplantation. Transplantation, 1993. 55(6): p. 1272–1277.
  • 12. Stephen I, Alexander, M.B., B.., Neil Smith, M.B., B.S., Min Hu, M.D., M.Med., et al, Chimerism and Tolerance in a Recipient of a Deceased-Donor Liver Transplant. NEJM, 2008. 358: p. 369-74.
  • 13. Mazariegos GV. Marino IR, Demetris AJ, Flynn B, Irish W, Michael JM, John J. Weaning of immunosuppression in liver transplant recipients. Transplantation, 1997. 27(63): p. 243-249.
  • 14 . Tryphonopoulos, P.Weppler D, Nishida S, Levi DM, Moon J, Tekin A. Madeline Velez, Danielle Rachel Neuman, Eddie Island, Gennaro Selvaggi, and Andreas G. Tzakis, Long-Term Follow-Up of 23 Operational Tolerant LiverTransplant Recipients. Transplantation, 2010. 90: p. 1556-1561.
  • 15. Tryphonopoulos P, Ruiz P, Weppler D, Nishida S, Levi DM, Moon J. Long-term follow-up of 23 operational tolerant liver transplant recipients. Transplantation. 2010 Dec 27;90(12):1556-61.
  • 16. Jain A, Mazariegos G, Pokharna R, Parizhskaya M, Kashyap R, Kosmach-Park B. The Absence of Chronic Rejection in Pediatric Primary Liver Transplant Patients Who Are Maintained on Tacrolimus-Based Immunosuppression: A Long-Term Analysis Transplantation. 2003 Apr 15;75(7):1020-5.
  • 17. Pilat N, W.T, Transplantation tolerance through mixed chimerism. Nat Rev Nephrol, 2010. 6(10): p. 594-605.
  • 18. Kinsella FAM, Zuo J, Inman CF, Pearce H, Maggs L, Eldershaw SE.Mixed chimerism established by hematopoietic stem cell transplantation is maintained by host and donor T regulatory cells. Blood Adv. 2019 Mar 12;3(5):734-743.
  • 19. Rickert CG, Markmann JF. Current state of organ transplant tolerance. Curr Opin Organ Transplant. 2019 Aug;24(4):441-450.
  • 20. Bishop GA, P., Bertolino PD, David G. Bowen, Geoffrey W. McCaughan. Tolerance in liver transplantation. Best Practice & Research Clinical Gastroenterology, 2012. 26: p. 73-84.
  • 21. Szabolcs P, W.J.B,. Thomson AV, Tolerance after solid organ and hematopoietic cell transplantation. Biol Blood Marrow Transplant, 2012. 18: p. 193-200.
  • 22. Harmon C, Sanchez-Fueyo A, O'Farrelly C, Houlihan DD. Natural Killer Cells and Liver Transplantation: Orchestrators of Rejection or Tolerance? Am J Transplant. 2016 Mar;16(3):751-7.
  • 23. Abrol N, Jadlowiec CC, Taner T. Revisiting the liver's role in transplant alloimmunity. World J Gastroenterol. 2019 Jul 7;25(25):3123-3135.
There are 23 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Articles
Authors

Murat Çağ 0000-0003-4006-4079

Sevda Yeşim Özdemir 0000-0002-4398-2767

Publication Date September 13, 2021
Submission Date October 15, 2020
Acceptance Date March 24, 2021
Published in Issue Year 2021 Volume: 28 Issue: 3

Cite

Vancouver Çağ M, Özdemir SY. KARACİĞER TRANSPLANTASYONUNDA MİKROKİMERİZM OLMADAN TOLERANS MÜMKÜN MÜDÜR?. Med J SDU. 2021;28(3):403-10.

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