title: Monitoring peripheral blood CD4+ adenosine triphosphate activity after living donor liver transplantation: impact of combination assays of immune function and CYP3A5 genotype.
abstract: 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 2002-2009 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).
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-0001, Japan. mizunos@clin.medic.mie-u.ac.jp
authors.forename: Shugo
authors.initials: S
authors.lastname: Mizuno
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamada
authors.forename: Kaname
authors.initials: K
authors.lastname: Nakatani
authors.forename: Masashi
authors.initials: M
authors.lastname: Kishiwada
authors.forename: Masanobu
authors.initials: M
authors.lastname: Usui
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Masami
authors.initials: M
authors.lastname: Tabata
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Junji
authors.initials: J
authors.lastname: Nishioka
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Muraki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okuda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nobori
authors.forename: Shuji
authors.initials: S
authors.lastname: Isaji
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood* / Q000276:immunology; D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000097:blood / Q000276:immunology*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007111:Immunity, Cellular; D016031:Liver Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; D000255:Adenosine Triphosphate; D004247:DNA; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A