title: Cytokine kinetics profiling in pediatric renal transplant recipients.
abstract: Pediatric renal transplant recipients experience side effects of immunosuppression. Few immunoassays exist which can assess the adequacy of immunosuppression. We developed a CKT, whereby cytokine levels are measured in a five-day mixed lymphocyte reaction. We describe the in vitro cytokine responses to donor and third-party antigen in a pilot study of nine children after living-donor renal transplantation. The CKT identified five patterns of IFN-gamma secretion relative to donor and third-party alloantigen: no response to alloantigen (n = 2), hypo-response to donor (n = 3), equal response (n = 1), hyper-response to donor (n = 1), and intermediate response (n = 2). IL-2 and IL-13 patterning correlated with IFN-gamma expression. Two of nine subjects had acute rejection, which correlated with intermediate and hyper-responsive profiles. No rejection occurred during immunosuppression or donor-specific hypo-responsiveness. Significant immunosuppression was universal early after transplantation. Two of four children showed strong pretransplant responses to donor, which were regained three months post-transplant, and associated with rejection in one subject. The CKT reflects the level of immunosuppression and may offer a method to assess the adequacy of immunosuppression. A pattern of complete non-responsiveness or hypo-responsiveness correlated with lack of acute rejection. The CKT may prove useful in titrating immunosuppression and in improving live donor selection.
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792, USA. sv.haustein@hosp.wisc.edu
authors.forename: Silke V
authors.initials: SV
authors.lastname: Niederhaus
authors.forename: Debra D
authors.initials: DD
authors.lastname: Bloom
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chang
authors.forename: Huaizhong
authors.initials: H
authors.lastname: Hu
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Bartosh
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Knechtle
mesh_terms: D002648:Child; D016207:Cytokines / Q000276:immunology* / Q000493:pharmacokinetics; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007118:Immunoassay; D007166:Immunosuppressive Agents / Q000276:immunology / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D010865:Pilot Projects
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents