2007TransplantationRequires access

Pretransplant Cellular Alloimmunity as Assessed by a Panel of Reactive T Cells Assay Correlates With Acute Renal Graft Rejection

Emilio D. Poggio, Joshua J. Augustine, Michael J. Clemente, Joel M. Danzig, Nina Volokh, Martin S. Zand, Donald E. Hricik, Peter S. Heeger

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Abstract

BACKGROUND: The panel reactive antibody test (PRA) is an established method for assessing posttransplant risk of immune-mediated graft injury. The panel of reactive T cell assay (PRT) in which transplant candidates' peripheral blood mononuclear cells are tested for reactivity to a panel of allogenic stimulator cells by the IFN-gamma enzyme-linked immunosorbent spot assay analogously assesses the strength of the pretransplant effector-memory alloreactive T cell repertoire. METHODS: PRT assays were performed in 30 kidney transplant candidates and results were correlated with acute rejection (AR). A positive PRT assay was defined as a response to at least 75% of the stimulators tested. RESULTS: A positive pretransplant PRT test was observed in 11 of 30 (37%) patients, and AR within 1 year posttransplantation was seen in 7 of 30 (23%) subjects. Six of the seven (86%) patients with AR were PRT-positive (P=0.01) whereas only one of seven (14%) patients with a PRA greater than 15% had AR. The mean pretransplant PRT percentage was 40% for patients with no AR versus 81% for patients with AR (P=0.01). Estimated glomerular filtration rate (mL/min/1.73 m2) showed a trend towards a lower value in PRT-positive (48+/-15) versus PRT-negative (55+/-13) individuals. CONCLUSIONS: The data suggest that pretransplant PRT screening can identify patients at risk for posttransplant cellular immune mediated graft injury despite the absence of humoral allosensitization. Once confirmed by larger prospective trials, PRT screening could be used to guide clinical decision-making with regard to choosing donor organs and individualizing immunosuppression regimens.

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BACKGROUND: The panel reactive antibody test (PRA) is an established method for assessing posttransplant risk of immune-mediated graft injury. The panel of reactive T cell assay (PRT) in which transplant candidates' peripheral blood mononuclear cells are tested for reactivity to a panel of allogenic stimulator cells by the IFN-gamma enzyme-linked immunosorbent spot assay analogously assesses the strength of the pretransplant effector-memory alloreactive T cell repertoire. METHODS: PRT assays were performed in 30 kidney transplant candidates and results were correlated with acute rejection (AR). A positive PRT assay was defined as a response to at least 75% of the stimulators tested. RESULTS: A positive pretransplant PRT test was observed in 11 of 30 (37%) patients, and AR within 1 year posttransplantation was seen in 7 of 30 (23%) subjects. Six of the seven (86%) patients with AR were PRT-positive (P=0.01) whereas only one of seven (14%) patients with a PRA greater than 15% had AR. The mean pretransplant PRT percentage was 40% for patients with no AR versus 81% for patients with AR (P=0.01). Estimated glomerular filtration rate (mL/min/1.73 m2) showed a trend towards a lower value in PRT-positive (48+/-15) versus PRT-negative (55+/-13) individuals. CONCLUSIONS: The data suggest that pretransplant PRT screening can identify patients at risk for posttransplant cellular immune mediated graft injury despite the absence of humoral allosensitization. Once confirmed by larger prospective trials, PRT screening could be used to guide clinical decision-making with regard to choosing donor organs and individualizing immunosuppression regimens.

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Available abstract

BACKGROUND: The panel reactive antibody test (PRA) is an established method for assessing posttransplant risk of immune-mediated graft injury. The panel of reactive T cell assay (PRT) in which transplant candidates' peripheral blood mononuclear cells are tested for reactivity to a panel of allogenic stimulator cells by the IFN-gamma enzyme-linked immunosorbent spot assay analogously assesses the strength of the pretransplant effector-memory alloreactive T cell repertoire. METHODS: PRT assays were performed in 30 kidney transplant candidates and results were correlated with acute rejection (AR). A positive PRT assay was defined as a response to at least 75% of the stimulators tested. RESULTS: A positive pretransplant PRT test was observed in 11 of 30 (37%) patients, and AR within 1 year posttransplantation was seen in 7 of 30 (23%) subjects. Six of the seven (86%) patients with AR were PRT-positive (P=0.01) whereas only one of seven (14%) patients with a PRA greater than 15% had AR. The mean pretransplant PRT percentage was 40% for patients with no AR versus 81% for patients with AR (P=0.01). Estimated glomerular filtration rate (mL/min/1.73 m2) showed a trend towards a lower value in PRT-positive (48+/-15) versus PRT-negative (55+/-13) individuals. CONCLUSIONS: The data suggest that pretransplant PRT screening can identify patients at risk for posttransplant cellular immune mediated graft injury despite the absence of humoral allosensitization. Once confirmed by larger prospective trials, PRT screening could be used to guide clinical decision-making with regard to choosing donor organs and individualizing immunosuppression regimens.

Key concepts: Alloimmunity, Medicine, Panel reactive antibody, Internal medicine, Immunology, Kidney transplantation, Renal function, Immune system

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