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Pre-transplant donor reactive class II antibodies are as pathogenic as class I antibodies in primary renal allografts
S30
Abstracts
3.01 48-OR
PRA OR TRANSPLANTABILITY INDEX—WHAT DO OUR CLINICAL COLLEAGUES NEED? Gareth Page, Mieke van Dam, Alasdair Heads, Robert Vaughan Clinical Transplantation Laboratory, Guy’s Hospital, London, United Kingdom Clinicians are familiar with the term Panel Reactive Antibody (PRA), but do they really understand what it means? PRA is used to indicate the transplantability of a patient, but the increasing range of anti-HLA screening and identification techniques has made complement dependent cytotoxicity PRA obsolete: Does the PRA include HLA class II antibodies or take antibody isotype into account? Is the panel static or random? We would like to propose a novel way of assessing the transplantability of a patient. Like many other laboratories, we use a simple flow cytometry based antibody screening technique as the first line in antibody detection. If antibody is present we employ a range of techniques (CDC, ELISA and Flow) to define the specificity. The key to transplantability is not only PRA, but a combination of recipient HLA type (compared to the donor population) and antibody specificity (directed at HLA in the donor population). Using the UK guidelines for matching, the HLA antigen frequency (HLA A, B, DR) was calculated for local donors over a 3 year period. This was used to generate a phenotype score for patients on the transplant waiting list. Values ranged from 1 for HLA B70 (B71⫹72) to 50 for HLA A2. The computed score gives a matchability value for each patient. A score for antibody specificity, based on adding the phenotype score of each individual specificity, is subtracted from the matchability value, giving a Transplantability Index (TI) for each patient. The system applies to both national and local waiting lists. Antibody specificity must be determined, which reduces the number of unexpected positive crossmatches and reduces cold ischaemic time where kidneys are exported for sharing. Our TI gives clinicians precise information regarding the possibility of transplanting a particular patient.
3.01 49-OR
PRE-TRANSPLANT DONOR REACTIVE CLASS II ANTIBODIES ARE AS PATHOGENIC AS CLASS I ANTIBODIES IN PRIMARY RENAL ALLOGRAFTS Denise Pochinco,1 Howard Gebel,2 Robert Bray,2 Ian Gibson,1 David Rush,1 Martin Karpinski,1 John Jeffery,1 Peter Nickerson1 1Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada; 2Dept of Pathology, Emory University, Atlanta, GA There is much debate as to the significance (i.e. risk for acute humoral rejection and/or early graft loss) of donor reactive Class II antibodies detected pre-transplant in primary renal allografts, relative to the risk that donor reactive Class I antibodies portend. In the current study we compared the clinical outcomes of patients transplanted in the presence of donor reactive Class I or II HLA antibodies. Of 303 primary renal allografts transplanted between 1992–2003 (negative AHG-CDC T-cell and negative CDC B-cell crossmatch), 46 were retrospectively found to have Class I or Class II antibodies present in the pre-transplant sera by FlowPRA assessment. These 46 patients had the specificity of the HLA antibodies determined by flow using donor cells, as well as specificity and/or single antigen beads. The patients were segregated into 3 groups: Donor reactive Class I (n ⫽ 17), Class II (n ⫽ 10) or Controls (HLA antibodies present but none donor reactive (n ⫽ 19)). There was no difference in outcome between patients with donor reactive Class I or II antibodies; both had earlier and higher rates of rejection as well as graft loss compared to patients with pre-transplant antibodies that were not donor reactive (Table; * p⬍0.05 vs. Control). In conclusion, detection and specificity analysis of Class II antibodies should be pursued just as aggressively as Class I antibodies in the pre-transplant evaluation in order to optimize transplant management.
Group Class I (n ⫽ 17) Class II (n ⫽ 10) Control (n ⫽ 19)
Rejection ⬍28 days 15 (88%)* 7 (80%)* 4 (21%)
Day of Rejection 6 (1–19)* 5 (2–9)* 13 (8–19)
Humoral Graft Loss 5 (29%)* 3 (30%)* 0 (0%)
Day of Graft Loss 3 (1–12) 5 (2–9) na
Abstracts
3.01 48-OR
PRA OR TRANSPLANTABILITY INDEX—WHAT DO OUR CLINICAL COLLEAGUES NEED? Gareth Page, Mieke van Dam, Alasdair Heads, Robert Vaughan Clinical Transplantation Laboratory, Guy’s Hospital, London, United Kingdom Clinicians are familiar with the term Panel Reactive Antibody (PRA), but do they really understand what it means? PRA is used to indicate the transplantability of a patient, but the increasing range of anti-HLA screening and identification techniques has made complement dependent cytotoxicity PRA obsolete: Does the PRA include HLA class II antibodies or take antibody isotype into account? Is the panel static or random? We would like to propose a novel way of assessing the transplantability of a patient. Like many other laboratories, we use a simple flow cytometry based antibody screening technique as the first line in antibody detection. If antibody is present we employ a range of techniques (CDC, ELISA and Flow) to define the specificity. The key to transplantability is not only PRA, but a combination of recipient HLA type (compared to the donor population) and antibody specificity (directed at HLA in the donor population). Using the UK guidelines for matching, the HLA antigen frequency (HLA A, B, DR) was calculated for local donors over a 3 year period. This was used to generate a phenotype score for patients on the transplant waiting list. Values ranged from 1 for HLA B70 (B71⫹72) to 50 for HLA A2. The computed score gives a matchability value for each patient. A score for antibody specificity, based on adding the phenotype score of each individual specificity, is subtracted from the matchability value, giving a Transplantability Index (TI) for each patient. The system applies to both national and local waiting lists. Antibody specificity must be determined, which reduces the number of unexpected positive crossmatches and reduces cold ischaemic time where kidneys are exported for sharing. Our TI gives clinicians precise information regarding the possibility of transplanting a particular patient.
3.01 49-OR
PRE-TRANSPLANT DONOR REACTIVE CLASS II ANTIBODIES ARE AS PATHOGENIC AS CLASS I ANTIBODIES IN PRIMARY RENAL ALLOGRAFTS Denise Pochinco,1 Howard Gebel,2 Robert Bray,2 Ian Gibson,1 David Rush,1 Martin Karpinski,1 John Jeffery,1 Peter Nickerson1 1Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada; 2Dept of Pathology, Emory University, Atlanta, GA There is much debate as to the significance (i.e. risk for acute humoral rejection and/or early graft loss) of donor reactive Class II antibodies detected pre-transplant in primary renal allografts, relative to the risk that donor reactive Class I antibodies portend. In the current study we compared the clinical outcomes of patients transplanted in the presence of donor reactive Class I or II HLA antibodies. Of 303 primary renal allografts transplanted between 1992–2003 (negative AHG-CDC T-cell and negative CDC B-cell crossmatch), 46 were retrospectively found to have Class I or Class II antibodies present in the pre-transplant sera by FlowPRA assessment. These 46 patients had the specificity of the HLA antibodies determined by flow using donor cells, as well as specificity and/or single antigen beads. The patients were segregated into 3 groups: Donor reactive Class I (n ⫽ 17), Class II (n ⫽ 10) or Controls (HLA antibodies present but none donor reactive (n ⫽ 19)). There was no difference in outcome between patients with donor reactive Class I or II antibodies; both had earlier and higher rates of rejection as well as graft loss compared to patients with pre-transplant antibodies that were not donor reactive (Table; * p⬍0.05 vs. Control). In conclusion, detection and specificity analysis of Class II antibodies should be pursued just as aggressively as Class I antibodies in the pre-transplant evaluation in order to optimize transplant management.
Group Class I (n ⫽ 17) Class II (n ⫽ 10) Control (n ⫽ 19)
Rejection ⬍28 days 15 (88%)* 7 (80%)* 4 (21%)
Day of Rejection 6 (1–19)* 5 (2–9)* 13 (8–19)
Humoral Graft Loss 5 (29%)* 3 (30%)* 0 (0%)
Day of Graft Loss 3 (1–12) 5 (2–9) na