Preferential benefit of antibody induction therapy in kidney recipients with high pretransplant frequencies of donor-reactive interferon-gamma enzyme-linked immunosorbent spots.
BACKGROUND
The decision to use induction antibody therapy in kidney transplantation is often based on perceived patient risk, as no objective biomarker has been shown to predict the effectiveness of such therapy. Because pretransplant T-cell alloreactivity has been shown to increase the risk of poor posttransplant outcome, and because induction therapy is directed at alloreactive T cells, we hypothesized that antibody induction would preferentially benefit patients with high pretransplant antidonor T-cell immunity.


METHODS
In a retrospective analysis of 130 patients who had enrolled in an immune monitoring study, we correlated acute rejection rates, renal allograft function, and use of antibody induction therapy with donor-reactive interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) frequencies assessed pre and postkidney transplantation.


RESULTS
Of the 32 ELISPOT (+) patients, eight received induction therapy and had no rejection. Of the remaining 24 ELISPOT (+) patients with no induction therapy, acute rejection occurred in 11 (46%), (P=0.02). Twelve month glomerular filtration rate was significantly higher in the eight patients who received induction therapy (P=0.0001). Posttransplant conversion to a negative ELISPOT assay occurred in 86% of patients who received induction therapy vs. 35% of patients who did not (P=0.02). In the ELISPOT (-) cohort, acute rejection rates ( approximately 15%) and glomerular filtration rates were similar in the 98 patients regardless of induction therapy.


CONCLUSIONS
Our results suggest that antibody induction therapy preferentially benefits kidney transplant candidates with strong pretransplant donor-reactive cellular immunity. If confirmed prospectively, pretransplant ELISPOT assessments could be used to guide decision making regarding induction therapy.
Augustine
Joshua J
JJ
Division of Nephrology and Hypertension, University Hospitals Case Medical Center, Cleveland, OH, USA. Joshua.Augustine@UHhospitals.org
Poggio
Emilio D
ED
Heeger
Peter S
PS
Hricik
Donald E
DE
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000917:Antibody Formation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007371:Interferon-gamma / Q000032:analysis*; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors / Q000706:statistics & numerical data
D000906:Antibodies; D000911:Antibodies, Monoclonal; D007371:Interferon-gamma