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Neutrophils and lymphoid chimerism after adult living-related liver transplantation from a homozygous donor
Abstracts
S63
1.07 #38
NEUTROPHILS AND LYMPHOID CHIMERISM AFTER ADULT LIVING-RELATED LIVER TRANSPLANTATION FROM A HOMOZYGOUS DONOR Ali H. Hajeer,1 Samir Issa,2 Khalid Abdullah,2 Mohammed Awad,3 Abdelghani Tbakhi,3 Ahmad Askar,2 Abdulmajeed Abdulkareem.2 1Pathology, King Fahad National Guard Hospital, Riyadh, Saudi Arabia; 2Hepatobiliary Sciences, King Fahad National Guard Hospital, Riyadh, Saudi Arabia; 3Immunopathology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia Graft-versus host disease (GVHD) is a significant risk in liver transplant patients. The risk is even higher in cases of living-related liver transplant (LRLT). Donors homozygous at all HLA loci carry higher risk for GVHD. Here we present a case of LRLT, the recipient suffered from end stage liver disease and received a right lobe graft from his son. Eight months after the transplant, the patient developed profound bone marrow suppression. The patient was negative for CMV, Brucella, HHV6, HHV8, HBV, HCV and Parvovirus. No sign of GVHD was noted (skin and GI). The patient and donor were HLA typed by SSP. The donor was homozygous for all HLA loci while the patient shared the class II homozygosity and was heterozygous at the class I. Chimerism studies were prompted after noting that the neutrophils compartment of the patient were homozygous at all HLA loci. This initiated further studies of the PMN and lymphocytes by microsatellite analysis. A total of 15 microsatellites were analyzed. Results suggested that majority (75%) of the PMN cells and 45% of the lymphocytes were of donor origin. The patient was treated with G-CSF and his WBC counts returned to normal levels. Two and a half years post transplant and the patient did not develop GVHD, despite the high number of donor lymphocytes circulating in his blood stream. The only complaint he has now is the development of severe arthritis, which was treated with steroids. Whether this is a result of the GVHD or not, this is to be investigated.
1.07 #39
HYPERACUTE REJECTION OF A 0 HLA-MISMATCHED KIDNEY: A CASE STUDY Brian M. Susskind,1 Gregg Boothe,2 Kathleen Larimore,2 Peter Stastny,3 E. Steve Woodle.4 1Transplantation Immunology Division, Hoxworth Blood Center, Cincinnati, OH; 2Donor Testing and Reference Lab, Hoxworth Blood Center, Cincinnati, OH; 3Transplant Immunology Laboratory, University of Texas Southwestern Medical Center, Dallas, TX; 4Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH A lupus nephritis patient had previously lost a 4 ABDR-matched LRD kidney to accelerated acute rejection, despite a history of 0% CDC PRA. At the time of transplant #2, a 0 ABDR-mismatched cadaveric kidney, CDC PRA was 62% (IgG). Cytotoxic and flow cytometry crossmatches (XM) were negative; cold ischemia time was 20 hours. While the patient was still open, however the kidney becamee edematous and blue. Histopathology was consistent with hyperacute rejection (tubule necrosis, focal acute inflammation, congested glomeruli, fibrin thrombi). Repeat FCXMs were negative, even after pronase treatment. Undetected HLA mismatches were ruled out by allelic HLA typing for A,B,C,DR,DQ. ABO-incompatibility was ruled out: patient and donor were A1 subtype; patient was negative for antibodies to 20 other blood group antigens (e.g., anti-Lewis, Lutheran, Kell, Duffy). Sample mix-up was ruled out by HLA typing the nephrectomized donor kidney. Pre- and posttransplant sera were negative for antibodies against cardiolipin, phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine, as well as anti-platelet specific antigens.. Anti-endothelial cell antibody analyses by ELISA with recombinant MICA*001, MICA*002, MICA*004, MICA*008 and MICA*009, were likewise negative; recipient and donor both appear to be MICA*008 homozygous. In summary, this lupus nephritis patient developed accelerated acute rejection following a 4 ABDR LRD primary transplant despite a history of 0% CDC PRA, and a repeat renal transplant from a 0 ABDR-mismatched cadaveric donor was lost due to hyperacute rejection despite negative flow cytometry crossmatches. No reasons for recurrent early graft rejection were forthcoming; studies are still in progress to identify the cause.
S63
1.07 #38
NEUTROPHILS AND LYMPHOID CHIMERISM AFTER ADULT LIVING-RELATED LIVER TRANSPLANTATION FROM A HOMOZYGOUS DONOR Ali H. Hajeer,1 Samir Issa,2 Khalid Abdullah,2 Mohammed Awad,3 Abdelghani Tbakhi,3 Ahmad Askar,2 Abdulmajeed Abdulkareem.2 1Pathology, King Fahad National Guard Hospital, Riyadh, Saudi Arabia; 2Hepatobiliary Sciences, King Fahad National Guard Hospital, Riyadh, Saudi Arabia; 3Immunopathology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia Graft-versus host disease (GVHD) is a significant risk in liver transplant patients. The risk is even higher in cases of living-related liver transplant (LRLT). Donors homozygous at all HLA loci carry higher risk for GVHD. Here we present a case of LRLT, the recipient suffered from end stage liver disease and received a right lobe graft from his son. Eight months after the transplant, the patient developed profound bone marrow suppression. The patient was negative for CMV, Brucella, HHV6, HHV8, HBV, HCV and Parvovirus. No sign of GVHD was noted (skin and GI). The patient and donor were HLA typed by SSP. The donor was homozygous for all HLA loci while the patient shared the class II homozygosity and was heterozygous at the class I. Chimerism studies were prompted after noting that the neutrophils compartment of the patient were homozygous at all HLA loci. This initiated further studies of the PMN and lymphocytes by microsatellite analysis. A total of 15 microsatellites were analyzed. Results suggested that majority (75%) of the PMN cells and 45% of the lymphocytes were of donor origin. The patient was treated with G-CSF and his WBC counts returned to normal levels. Two and a half years post transplant and the patient did not develop GVHD, despite the high number of donor lymphocytes circulating in his blood stream. The only complaint he has now is the development of severe arthritis, which was treated with steroids. Whether this is a result of the GVHD or not, this is to be investigated.
1.07 #39
HYPERACUTE REJECTION OF A 0 HLA-MISMATCHED KIDNEY: A CASE STUDY Brian M. Susskind,1 Gregg Boothe,2 Kathleen Larimore,2 Peter Stastny,3 E. Steve Woodle.4 1Transplantation Immunology Division, Hoxworth Blood Center, Cincinnati, OH; 2Donor Testing and Reference Lab, Hoxworth Blood Center, Cincinnati, OH; 3Transplant Immunology Laboratory, University of Texas Southwestern Medical Center, Dallas, TX; 4Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH A lupus nephritis patient had previously lost a 4 ABDR-matched LRD kidney to accelerated acute rejection, despite a history of 0% CDC PRA. At the time of transplant #2, a 0 ABDR-mismatched cadaveric kidney, CDC PRA was 62% (IgG). Cytotoxic and flow cytometry crossmatches (XM) were negative; cold ischemia time was 20 hours. While the patient was still open, however the kidney becamee edematous and blue. Histopathology was consistent with hyperacute rejection (tubule necrosis, focal acute inflammation, congested glomeruli, fibrin thrombi). Repeat FCXMs were negative, even after pronase treatment. Undetected HLA mismatches were ruled out by allelic HLA typing for A,B,C,DR,DQ. ABO-incompatibility was ruled out: patient and donor were A1 subtype; patient was negative for antibodies to 20 other blood group antigens (e.g., anti-Lewis, Lutheran, Kell, Duffy). Sample mix-up was ruled out by HLA typing the nephrectomized donor kidney. Pre- and posttransplant sera were negative for antibodies against cardiolipin, phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine, as well as anti-platelet specific antigens.. Anti-endothelial cell antibody analyses by ELISA with recombinant MICA*001, MICA*002, MICA*004, MICA*008 and MICA*009, were likewise negative; recipient and donor both appear to be MICA*008 homozygous. In summary, this lupus nephritis patient developed accelerated acute rejection following a 4 ABDR LRD primary transplant despite a history of 0% CDC PRA, and a repeat renal transplant from a 0 ABDR-mismatched cadaveric donor was lost due to hyperacute rejection despite negative flow cytometry crossmatches. No reasons for recurrent early graft rejection were forthcoming; studies are still in progress to identify the cause.