Pre-transplant IFN-gamma ELISPOTs are associated with post-transplant renal function in African American renal transplant recipients.
Final crossmatch testing is routinely used to assess the risk of antibody-mediated graft injury/rejection post-transplant. Analogously, we postulated that quantitative measurements of anti-donor effector/memory T cells pre-transplant would independently assess post-transplant risk. To address this hypothesis, we determined the frequencies of pre-transplant, donor-specific interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spots (ELISPOTs) and correlated the results with post-transplant outcomes in 37 African American recipients of deceased donor kidney transplants treated with tacrolimus- and sirolimus-based immunosuppression. A positive ELISPOT test (>25 spots/300,000 cells) was detected in 14 (38%) of 37 patients. The incidence of biopsy-proven acute rejection was 50% (7/14) in ELISPOT-positive versus 17% (4/23) in ELISPOT-negative patients (p=0.036). Calculated glomerular filtration rate (MDRD) at 12 months was 37+/-16 mL/min in ELISPOT-positive versus 55+/-20 mL/min in ELISPOT-negative patients (p=0.01). ELISPOT status remained a correlate of allograft function at 12 months by linear regression analysis (p=0.001), independent of rejection and other contributing variables. Pre-transplant donor-directed IFN-gamma ELISPOT assessment of anti-donor cellular immunity may function as a 'cellular crossmatch' and independently correlates with renal allograft function in African Americans receiving tacrolimus- and sirolimus-based immunosuppression.
Division of Nephrology, University Hospitals of Cleveland, Cleveland, Ohio, USA. joshua.augustine@uhhs.com
Joshua J
JJ
Augustine
David S
DS
Siu
Michael J
MJ
Clemente
James A
JA
Schulak
Peter S
PS
Heeger
Donald E
DE
Hricik
D001741:Black or African American; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000032:analysis* / Q000378:metabolism; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D014019:Tissue Donors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D020123:Sirolimus; D016559:Tacrolimus