Monitoring peripheral blood CD4+ adenosine triphosphate activity after living donor liver transplantation: impact of combination assays of immune function and CYP3A5 genotype

详细信息    查看全文

• 作者：Shugo Mizuno (1)
  Takashi Hamada (1)
  Kaname Nakatani (2)
  Masashi Kishiwada (1)
  Masanobu Usui (1)
  Hiroyuki Sakurai (1)
  Masami Tabata (1)
  Yuko Sakamoto (3)
  Junji Nishioka (3)
  Yuichi Muraki (4)
  Masahiro Okuda (4)
  Tsutomu Nobori (2)
  Shuji Isaji (1)
  
• 关键词：Living donor liver transplantation ; Calcineurin inhibitor ; Cytochrome P450 3A genotype ; Immune functional assay
• 刊名：Journal of Hepato-Biliary-Pancreatic Sciences
• 出版年：2011
• 出版时间：March 2011
• 年：2011
• 卷：18
• 期：2
• 页码：226-234
• 全文大小：257KB
• 参考文献：1. Shiraga T, Matsuda H, Nagase K, Iwasaki K, Noda K, Yamazaki H, Shimada T, Funae Y. Metabolism of FK506, a potent immunosuppressive agent, by cytochrome P450 3A enzymes in rat, dog and human liver microsomes. Biochem Pharmacol. 1994;47:727-5. CrossRef
  2. Hesselink DA, van Schaik RH, van der Heiden IP, van der Werf M, Gregoor PJ, Lindemans J, Weimar W, van Gelder T. Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther. 2003;74:245-4. CrossRef
  3. Kamdem LK, Streit F, Zanger UM, Brockmoller J, Oellerich M, Armstrong VW, Wojnowski L. Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus. Clin Chem. 2005;51:1374-1. CrossRef
  4. Dai Y, Hebert MF, Isoherranen N, Davis CL, Marsh C, Shen DD, Thummel KE. Effect of CYP3A5 polymorphism on tacrolimus metabolic clearance in vitro. Drug Metab Dispos. 2006;34:836-7. CrossRef
  5. Tada H, Tsuchiya N, Satoh S, Kagaya H, Li Z, Sato K, et al. Impact of CYP3A5 and MDR1(ABCB1) C3435T polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplant Proc. 2005;37:1730-. CrossRef
  6. Mourad M, Mourad G, Wallemacq P, Garrigue V, Van Bellingen C, Van Kerckhove V, et al. Sirolimus and tacrolimus trough concentrations and dose requirements after kidney transplantation in relation to CYP3A5 and MDR1 polymorphisms and steroids. Transplantation. 2005;80:977-4. CrossRef
  7. Buttgereit F, Burmester GR, Brand MD. Bioenergetics of immune functions: fundamental and therapeutic aspects. Immunol Today. 2000;21:192-. CrossRef
  8. Kowalski RJ, Post DR, Mannon RB, Sebastian A, Wright HI, Sigle G, et al. Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay. Transplantation. 2006;82:663-. CrossRef
  9. Kowalski R, Post D, Schneider MC, Britz J, Thomas J, Deierhoi M, et al. Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management. Clin Transplant. 2003;17:77-8. CrossRef
  10. Fukuen S, Fukuda T, Maune H, Ikenaga Y, Yamamoto I, Inaba T, Azuma J, et al. Novel detection assay by PCR–RFLP and frequency of the / CYP3A5 SNPs, / CYP3A5*3 and / *6, in a Japanese population. Pharmacogenetics. 2002;12:331-. CrossRef
  11. Armstrong VW, Oellerich M. New developments in the immunosuppressive drug monitoring of cyclosporine, tacrolimus, and azathioprine. Clin Biochem. 2001;34(1):9-6. CrossRef
  12. Zeevi A, Britz JA, Bentlejewski CA, Guaspari D, Tong W, Bond G, et al. Monitoring immune function during tacrolimus tapering in small bowel transplant recipients. Transpl Immunol. 2005;15:17-4. CrossRef
  13. Mendler M, Kwok H, Franco E, Baron P, Weissman J, Ojogho O, et al. Monitoring peripheral blood CD4+ adenosine triphosphate activity in a liver transplant cohort: insight into the interplay between hepatitis C virus infection and cellular immunity. Liver Transpl. 2008;14(9):1313-2. CrossRef
  14. Chinnakotla S, Davis GL, Vasani S, Kim P, Tomiyama K, Sanchez E, et al. Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation. Liver Transpl. 2009;15(12):1834-2. CrossRef
  15. Cabrera R, Ararat M, Soldevila-Pico C, Dixon L, Pan JJ, Firpi R, et al. Using an immune functional assay to differentiate acute cellular rejection from recurrent hepatitis C in liver transplant patients. Liver Transpl. 2009;15(2):216-2. CrossRef
  16. Tahara H, Tanaka Y, Ishiyama K, Ide K, Shishida M, Irei T, et al. Successful hepatitis B vaccination in liver transplant recipients with donor-specific hyporesponsiveness. Transpl Int. 2009;22(8):805-3. CrossRef
  17. Jun KR, Lee W, Jang MS, Chun S, Song GW, Park KT, et al. Tacrolimus concentrations in relation to CYP3A and ABCB1 polymorphisms among solid organ transplant recipients in Korea. Transplantation. 2009;87(8):1225-1. CrossRef
  18. Hosohata K, Masuda S, Yonezawa A, Sugimoto M, Takada Y, Kaido T, et al. Absence of influence of concomitant administration of rabeprazole on the pharmacokinetics of tacrolimus in adult living-donor liver transplant patients: a case–control study. Drug Metab Pharmacokinet. 2009;24(5):458-3. CrossRef
  19. Usui M, Isaji S, Kobayashi M, Osawa I, Iida T, Sakurai H, et al. Selection of calcineurin inhibitar after living-donor liver transplantation based on CYP3A5 gene polymorphism: attempt of tailor-made treatment introduction. Am J Transplant. 2007;7[Suppl 2]:1562.
  
• 作者单位：Shugo Mizuno (1)
  Takashi Hamada (1)
  Kaname Nakatani (2)
  Masashi Kishiwada (1)
  Masanobu Usui (1)
  Hiroyuki Sakurai (1)
  Masami Tabata (1)
  Yuko Sakamoto (3)
  Junji Nishioka (3)
  Yuichi Muraki (4)
  Masahiro Okuda (4)
  Tsutomu Nobori (2)
  Shuji Isaji (1)
  
  1. Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
  2. Department of Molecular and Laboratory Medicine, Mie University School of Medicine, Tsu, Mie, Japan
  3. Central Laboratory, Mie University School of Medicine, Tsu, Mie, Japan
  4. Department of Pharmacy, Mie University School of Medicine, Tsu, Mie, Japan
  

文摘

Background The immune response after living donor liver transplantation (LDLT) was evaluated, with specific attention focused on the inter-relationship among clinical conditions, pharmacokinetics of tacrolimus, and cytochrome P450 3A5 (CYP3A5) genotypes. Methods Forty 40 adult patients who underwent LDLT in the period 2002-009 were enrolled in the study. Peripheral blood was collected from these patients between June 2009 and December 2009 and analyzed for CD4+ adenosine triphosphate (ATP) activity (ImmuKnow assay), tacrolimus concentration, and CYP3A5 genotype. Based on the results of the ImmuKnow assay (i.e., strength of immune response), each patient was categorized into one of the three established zones of immune response: Group A (low response, n?=?13), Group B (moderate response, n?=?24), and Group C (strong response, n?=?3). Results There was no correlation between the concentration of tacrolimus and ATP levels in the blood. The patients in Group A required much higher tacrolimus doses to maintain the blood concentration, as evidenced by the tacrolimus concentration/dose (C/D) ratios in Group A being significantly lower than those in Group B. Almost half of the patients in Group A suffered from infectious complications. The C/D ratios were significantly lower in the six patients with the CYP3A5*1 allele than in the 14 patients with the CYP3A5*3 allele; one-half of the patients with the CYP3A5*1 allele belonged to Group A. Conclusions Our results demonstrate that the immunKnow assay of immune function is an excellent tool for monitoring immune response, especially in the patients with CYP3A5*1 allele (expressors).