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53-W: Acute humoral rejection mediated by donor reactive anti-endothelial antibodies idntified using xmone™
Abstracts
S127
53-W
ACUTE HUMORAL REJECTION MEDIATED BY DONOR REACTIVE ANTI-ENDOTHELIAL ANTIBODIES IDNTIFIED USING XMONETM. Nicholas DiPaola, Jon Von Viger, Patrick Adams, Gregg Hadley. Transplant, Ohio State University Medical Center, Columbus, OH, USA. Some cases of acute antibody mediated rejection have been found in patients having no detectable anti-HLA antibodies. A new assay attempts to identify these non-HLA antibodies using endothelial precursor cells from a donor as an alternative target to traditional lymphocytes. The current case study demonstrates the utility of this assay. A living related donor recipient pair was recently evaluated for renal transplant. Tests included flow based PRA and 3-color flow cross match. The patient-pair was also evaluated using the XM-OneTM screening kit. This method employs magnetic beads coated with an antibody to Tie-2, an antigen found on circulating endothelial progenitor cells. The kit magnetically isolates the progenitor cells from blood and uses them as a target in a flow based cross match. The recipient, a 26 year old female, was shown to be negative for both class I and class II antibody against her donor by 3-color flow cross match. She was also shown to have a 0% PRA but did have a positive anti-endothelial cross match against her donor but not a third party donor using the XM-OneTM kit. The transplant was performed with Thymoglobulin induction therapy and steroid taper. Early graft function was good but on post-op day 9, rising creatinine caused a renal biopsy to be performed which demonstrated acute humoral rejection with C4d deposition. Post-transplant analysis still failed to demonstrate any anti-HLA antibodies despite the presence of acute humoral rejection. We conclude that preexisting antibodies directed against molecules other than HLA can mediate rejection episodes and technologies such as the current one will become increasingly important in pre-screening donors and recipients for renal transplants.
54-W
IMMUNE FUNCTION ASSAY: AN ADJUNCT TO TREATMENT OF AN EXTREMELY IMMUNE COMPROMISED HEART/LIVER TRANSPLANT PATIENT. Linda Peel,1 Tracie Curtis,1 Brad Persing,1 Janet Tuttle-Newhall,1 Barbara Burgess,1 Nancy Reinsmoen,2 Dong-Feng Chen.1 1Duke University Medical Center, Durham, NC; 2Cedars Sinai Medical Center, Los Angeles, CA. The Immune Function Assay (IFA) is a cellular assay that indirectly monitors CD4 activity by measuring ATP production in response to PHA stimulation. The assay reflects immune status during drug monitoring therapy or altered immune conditions. Serial analysis of a heart/liver transplant patient’s immune function was determined twelve times in one year. Use of the IFA began approximately one month after transplant and played an integral role when monitoring treatment of this patient. Other parameters observed at each test point include WBC count, therapeutic drug monitoring, biopsies, infections and other factors supporting assay observations. The responses ranged from 3 to 205 ng/ml ATP. Although it never reached the moderate or high range (226 to 524), there were still at least 5 mild rejections confirmed by biopsy. The WBC ranged from 47 to 2.8 ⫻ 10^6. After the transplant there were infections with yeast, CMV, klebsiella, enteroccocus, E. coli, C. difficile, staph, glandular, urinary, rectal, liver, lung, septicemia, diarrhea, fever, parvovirus, nonseptate fungal hyphae, and massive GI bleed. Some antibiotics and drugs used were prednisone, prograf, levofloxacin, ceftriaxone, septra, daptomycin, ertapenam, zyvox, CIPRO, flagel, ganciclovir, pentamidine, and abelcet. Immune response could not be gauged by conventional methods because of many varying factors. The expected increase in response during rejection was not observed; however, the status of the immune system response did seem to correlate with the IFA. This patient died from infection and liver failure with the last immune function result being 29 ng/ml.
S127
53-W
ACUTE HUMORAL REJECTION MEDIATED BY DONOR REACTIVE ANTI-ENDOTHELIAL ANTIBODIES IDNTIFIED USING XMONETM. Nicholas DiPaola, Jon Von Viger, Patrick Adams, Gregg Hadley. Transplant, Ohio State University Medical Center, Columbus, OH, USA. Some cases of acute antibody mediated rejection have been found in patients having no detectable anti-HLA antibodies. A new assay attempts to identify these non-HLA antibodies using endothelial precursor cells from a donor as an alternative target to traditional lymphocytes. The current case study demonstrates the utility of this assay. A living related donor recipient pair was recently evaluated for renal transplant. Tests included flow based PRA and 3-color flow cross match. The patient-pair was also evaluated using the XM-OneTM screening kit. This method employs magnetic beads coated with an antibody to Tie-2, an antigen found on circulating endothelial progenitor cells. The kit magnetically isolates the progenitor cells from blood and uses them as a target in a flow based cross match. The recipient, a 26 year old female, was shown to be negative for both class I and class II antibody against her donor by 3-color flow cross match. She was also shown to have a 0% PRA but did have a positive anti-endothelial cross match against her donor but not a third party donor using the XM-OneTM kit. The transplant was performed with Thymoglobulin induction therapy and steroid taper. Early graft function was good but on post-op day 9, rising creatinine caused a renal biopsy to be performed which demonstrated acute humoral rejection with C4d deposition. Post-transplant analysis still failed to demonstrate any anti-HLA antibodies despite the presence of acute humoral rejection. We conclude that preexisting antibodies directed against molecules other than HLA can mediate rejection episodes and technologies such as the current one will become increasingly important in pre-screening donors and recipients for renal transplants.
54-W
IMMUNE FUNCTION ASSAY: AN ADJUNCT TO TREATMENT OF AN EXTREMELY IMMUNE COMPROMISED HEART/LIVER TRANSPLANT PATIENT. Linda Peel,1 Tracie Curtis,1 Brad Persing,1 Janet Tuttle-Newhall,1 Barbara Burgess,1 Nancy Reinsmoen,2 Dong-Feng Chen.1 1Duke University Medical Center, Durham, NC; 2Cedars Sinai Medical Center, Los Angeles, CA. The Immune Function Assay (IFA) is a cellular assay that indirectly monitors CD4 activity by measuring ATP production in response to PHA stimulation. The assay reflects immune status during drug monitoring therapy or altered immune conditions. Serial analysis of a heart/liver transplant patient’s immune function was determined twelve times in one year. Use of the IFA began approximately one month after transplant and played an integral role when monitoring treatment of this patient. Other parameters observed at each test point include WBC count, therapeutic drug monitoring, biopsies, infections and other factors supporting assay observations. The responses ranged from 3 to 205 ng/ml ATP. Although it never reached the moderate or high range (226 to 524), there were still at least 5 mild rejections confirmed by biopsy. The WBC ranged from 47 to 2.8 ⫻ 10^6. After the transplant there were infections with yeast, CMV, klebsiella, enteroccocus, E. coli, C. difficile, staph, glandular, urinary, rectal, liver, lung, septicemia, diarrhea, fever, parvovirus, nonseptate fungal hyphae, and massive GI bleed. Some antibiotics and drugs used were prednisone, prograf, levofloxacin, ceftriaxone, septra, daptomycin, ertapenam, zyvox, CIPRO, flagel, ganciclovir, pentamidine, and abelcet. Immune response could not be gauged by conventional methods because of many varying factors. The expected increase in response during rejection was not observed; however, the status of the immune system response did seem to correlate with the IFA. This patient died from infection and liver failure with the last immune function result being 29 ng/ml.