title: Interferon Gamma ELISPOT Testing as a Risk-Stratifying Biomarker for Kidney Transplant Injury: Results From the CTOT-01 Multicenter Study.
abstract: Previous studies suggest that quantifying donor-reactive memory T cells prior to kidney transplantation by interferon gamma enzyme-linked immunosorbent spot assay (IFNγELISPOT) can assist in assessing risk of posttransplant allograft injury. Herein, we report an analysis of IFNγELISPOT results from the multicenter, Clinical Trials in Organ Transplantation-01 observational study of primary kidney transplant recipients treated with heterogeneous immunosuppression. Within the subset of 176 subjects with available IFNγELISPOT results, pretransplant IFNγELISPOT positivity surprisingly did not correlate with either the incidence of acute rejection (AR) or estimated glomerular filtration rate (eGFR) at 6- or 12-month. These unanticipated results prompted us to examine potential effect modifiers, including the use of T cell-depleting, rabbit anti-thymocyte globulin (ATG). Within the no-ATG subset, IFNγELISPOT(neg) subjects had higher 6- and 12-month eGFRs than IFNγELISPOT(pos) subjects, independent of biopsy-proven AR, peak PRA, human leukocyte antigen mismatches, African-American race, donor source, and recipient age or gender. In contrast, IFNγELISPOT status did not correlate with posttransplant eGFR in subjects given ATG. Our data confirm an association between pretransplant IFNγELISPOT positivity and lower posttransplant eGFR, but only in patients who do not receive ATG induction. Controlled studies are needed to test the hypothesis that ATG induction is preferentially beneficial to transplant candidates with high frequencies of donor-reactive memory T cells.
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH.
authors.forename: D E
authors.initials: DE
authors.lastname: Hricik
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH.
authors.forename: J
authors.initials: J
authors.lastname: Augustine
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Nickerson
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: R N
authors.initials: RN
authors.lastname: Formica
authors.affiliation: Department of Medicine, Cleveland Clinic, Cleveland, OH.
authors.forename: E D
authors.initials: ED
authors.lastname: Poggio
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Rush
authors.affiliation: Department of Surgery, Emory University Medical Center, Atlanta, GA.
authors.forename: K A
authors.initials: KA
authors.lastname: Newell
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: J
authors.initials: J
authors.lastname: Goebel
authors.affiliation: Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: I W
authors.initials: IW
authors.lastname: Gibson
authors.affiliation: Department of Immunology, Cleveland Clinic, Cleveland, OH.
authors.forename: R L
authors.initials: RL
authors.lastname: Fairchild
authors.affiliation: Rho, Chapel Hill, NC.
authors.forename: K
authors.initials: K
authors.lastname: Spain
authors.affiliation: Rho, Chapel Hill, NC.
authors.forename: D
authors.initials: D
authors.lastname: Iklé
authors.affiliation: Transplantation Branch, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD.
authors.forename: N D
authors.initials: ND
authors.lastname: Bridges
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York City, NY.
authors.forename: P S
authors.initials: PS
authors.lastname: Heeger
mesh_terms: D000328:Adult; D000818:Animals; D000961:Antilymphocyte Serum / Q000276:immunology; D015415:Biomarkers / Q000032:analysis*; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D011817:Rabbits; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D000961:Antilymphocyte Serum; D015415:Biomarkers; D007371:Interferon-gamma
keywords: Clinical research/practice; T cell biology; glomerular filtration rate (GFR); immunobiology; kidney transplantation/nephrology; rejection: acute; risk assessment/risk stratification; translational research/science