Cytokine kinetics profiling in pediatric renal transplant recipients.
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.
Niederhaus
Silke V
SV
Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792, USA. sv.haustein@hosp.wisc.edu
Bloom
Debra D
DD
Chang
Zhen
Z
Hu
Huaizhong
H
Bartosh
Sharon M
SM
Knechtle
Stuart J
SJ
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
D016207:Cytokines; D007166:Immunosuppressive Agents