title: Optimization of immunosuppressive therapy based on a multiparametric mixed lymphocyte reaction assay reduces infectious complications and mortality in living donor liver transplant recipients.
abstract: OBJECTIVE
  We investigated the clinical relevance of immune monitoring by a multiparametric mixed lymphocyte reaction (MLR) assay, wherein the number and phenotype of alloreactive precursors can be quantified by combining the results of carboxyfluorescein diacetate succinimidyl ester labeling and flow cytometry analysis.
  
  
  METHODS
  In 51 adult patients undergoing living donor liver transplantation (OLT), immunosuppressive drugs were dosed on the basis of immune monitoring by the MLR assay (optimized protocol: group O). In 64 other patients, the agents were prescribed according to empirical regimens (empirical protocol: group E). In group O, MLR assays were performed at 2- to 4-week intervals until 3 months after OLT and thereafter at 3- to 6-month intervals. Therapeutic adjustments for immunosuppressants were determined by tapering the doses in cases of anti-donor hyporesponsiveness for both CD4+ and CD8+ T-cell subsets.
  
  
  RESULTS
  The 1-year patient and graft survivals in groups O versus E were 90.2% versus 76.6%, respectively. The incidence of acute rejection episodes (ARE) among group O (13.7%) were lower than in cohort E (28.1%). None of the patients in group O while four patients (3%) in group E already have shown chronic rejection to date. The incidences of bacteremia and fungal infections in group O (9.8% and 7.5%, respectively) were lower than in cohort E (18.8% and 12.6%, respectively).
  
  
  CONCLUSIONS
  A multiparametric MLR assay may facilitate the development of adequate immunosuppressive regimens.
authors.affiliation: Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Tashiro
authors.forename: T
authors.initials: T
authors.lastname: Onoe
authors.forename: K
authors.initials: K
authors.lastname: Ide
authors.forename: K
authors.initials: K
authors.lastname: Ishiyama
authors.forename: H
authors.initials: H
authors.lastname: Ohdan
mesh_terms: D000208:Acute Disease; D000328:Adult; D001424:Bacterial Infections / Q000276:immunology / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016009:Chi-Square Distribution; D003141:Communicable Diseases / Q000276:immunology*; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007564:Japan; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D019520:Living Donors; D016015:Logistic Models; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods*; D015999:Multivariate Analysis; D009181:Mycoses / Q000276:immunology / Q000517:prevention & control; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D013388:Succinimides; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007166:Immunosuppressive Agents; D013388:Succinimides