DESENSITIZED RENAL TRANSPLANT RECIPIENTS SHOW REDUCED CELLULAR RESPONSES TO IN VITRO CHALLENGE.Room: 106
Pam M Kimball, Amy Mitchell, Anne King. Transplant Surgery, Medical College of Virginia Hospitals, Richmond, VA.
IVIG desensitization permits transplantation of sensitized renal recipients against allospecific compatibility barriers. It appears that IVIG regimens induce a sustained downregulation of alloantibody that facilitates graft success. However, the consequence of desensitization upon cellular immunity after transplantation has not been explored. We compared in vitro proliferative responses and cytokine upregulation between desensitized transplant recipients (IVIG) and non-sensitized patients (Control). Eleven patients were crossmatch incompatible with living donors and underwent a mean of 4.2 2.3 preoperative treatments with IVIG and plasmapheresis. Nine patients were successfully converted to compatible crossmatches and were transplanted. All patients received CellCept and Prograf. With a mean follow-up time of 17.6 6.7 months, we have 100% graft survival, 0% rejection and most recent sCr of 1.5 0.4. Peripheral lymphocytes were collected 12.5 9 months after transplantation and tested for proliferative response and intracytoplasmic expression of cytokines (IC) by flow cytometry following challenge with the superantigen staphylococcal enterotoxin b (SEB) and mixed lymphocyte reaction (MLR). Proliferation was markedly reduced among IVIG vs. Controls. Proliferative response among IVIG vs. Controls to SEB was 1.7 0.1 vs. 30.8 17.8 (p<0.05). Similarly, proliferative response to MLR for IVIG vs. Controls was 1 0.2 vs. 35.1 28.8 (p<0.05). IC measurement of cytokine upregulation following SEB challenge was statistically equivalent among IVIG vs. Controls: IL2 (1.5% 1.4 vs. 5.2% 2.1,p=0.07); TNF (33.6% 5.3 vs. 25.8% 8.7, p=ns); IFN (3.6% 3.6 vs. 1.9% 0.8, p=ns); IL10 (0.8% 0.1 vs. 2.6% 2.1, p=ns). In contrast, IC measurement of Th1 and Th2 cytokines following challenge with MLR was lower among IVIG vs. Controls: IL2 (0.4% 0.1 vs. 0.6% 0.1, p<.05); IFN (0.15% 0.1 vs. 0.45% 0.1, p<.05); IL 10 (0.4% 0.1 vs. 1.0% 0.2, p<.05). TNF levels were equivalent (9.1% 2.4 vs. 6.4% 2.2, p=ns). All IVIG patients maintained a compatible allocrossmatch. SUMMARY. One year after transplantation, desensitized renal transplant patients demonstrate in vitro hyporesponsiveness against superantigen and MLR. This suggests a downregulation in cellular immunity which may facilitate allograft survival.Whether the hyponsiveness is sustainable and would permit pharmacologic reduction requires additional study.
Keywords: Hyporeactivity; IVIG; Kidney transplantation; Tolerance
Monday, July 24, 2006 12:00 PM
Concurrent Session 1: HLA Antibodies: Presensitization (10:30 AM-12:30 PM)