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Correlation of pretransplant allosensitization with severity of rejection biopsy
Correlation of Pretransplant Allosensitization With Severity of Rejection Biopsy J. Clark, R. Kerman, B. Susskind, S. Katz, C. Van Buren, and B. Kahan
P
RETRANSPLANT histocompatibility testing is done to select compatible donor-recipient pairs for renal allotransplantation. Sera from prospective transplant recipients are routinely screened for the presence of HLA antibodies to determine the extent of HLA alloimmuization. Highly reactive sera are tested against donor target cells to assess recipient-donor incompatibility. The standard technique to screen sera for anti-HLA antibodies utilizes an anti-human globulin enhanced cytotoxicity assay (AHG) wherein patient sera are tested against a panel of target lymphocytes of known HLA type, and the panel reactive antibody (PRA) is determined.1 The AHG-determined PRA does not always represent anti-HLA antibody reactivity and does not always correlate with posttransplant clinical events.2 Using a recently described ELISA procedure (PRA-STAT) to identify IgG and anti-HLA antibodies, we reported a significant correlation of PRA-STAT . 10% and the occurrence of posttransplant rejection episodes.2 The purpose of the present study was to correlate the severity of renal damage, assessed by Banff biopsy rejection grade, to the pretransplant state of HLA allosensitization.
MATERIALS AND METHODS Pretransplant sera from 207 cyclosporine-prednisone treated primary recipients of cadaveric renal allografts were studied. All donors and recipients were ABO compatible. HLA A, B, C, and DR tissue typing was performed as previously described.2 All recipients were transplanted following a negative pretransplant AHG crossmatch.1 ELISA-detected IgG anti-HLA % PRA was determined by using the PRA-STAT kit (SangStat Medical Corporation, Menlo Park, Calif.)2 Data were reported as PRASTAT $ 10% or PRA-STAT , 10%. The % PRA was correlated to the occurrence of rejection episodes during the first 12 months posttransplant and to the severity of renal damage, assessed by Banff biopsy rejection grade.
Table 2. Correlation of Pretransplant PRA-STAT and the Number of Rejections PRA-STAT
Rejections/Rejectors
,10%
$10%
1.2 1 0.8
2.1 1 0.71
P , .02.
RESULTS
Patients with PRA-STAT $ 10% (n 5 68) experienced a 50% rejection frequency compared with the 26% rejection frequency for patients with PRA-STAT , 10% (n 5 139), P , .001. Table 1. Moreover, rejecting patients with pretransplant PRA-STAT $ 10% experienced significantly more rejections (2.1 6 0.71 vs 1.2 6 0.8, P , .02) than did those patients with pretransplant PRA-STAT , 10%, Table 2. Of great interest was the fact that patients whose transplant sera displayed PRA-STAT $ 10% had more severe acute rejections (56% vs 14%, P , .001, Banff grade III) and fewer mild acute rejections (9% vs 67%, P , .001, Banff grade I) than patients with PRA-STAT , 10% sera, as shown in Table 3. Those patients experiencing rejections experienced a 26% frequency of biopsy proven chronic rejection in PRA-STAT $ 10% vs an 8% frequency of chronic rejection in PRA-STAT , 19% patients, P , .05.
Table 3. Pretransplant (PRA–STAT) Versus Posttransplant Banff Grade Rejections PRA-STAT
Acute Rejection Severe (B–III) Mild (B–I)I)
,10%
$10%
P
5 24
19 3
,.001 ,.001
Table 1. Correlation of Pretransplant PRA-STAT With Rejection During the First 12 Months Postoperatively PRA-STAT Rejection
Yes No
,10%
36 103
x2 5 11.8; P , .001.
© 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
$10%
34 34
From the Departments of Pathology and Surgery, Division of Organ Transplantation, The University of Texas Medical School, Houston, Texas, USA. Address reprint requests to Dr J. Clark, Department of Pathology, University of Texas Medical School, 6431 Fannin, MSB 2.252, Houston, Texas 77030. 0041-1345/99/$–see front matter PII S0041-1345(98)01755-2 751
Transplantation Proceedings, 31, 751–752 (1999)
752
Finally, patients whose pretransplant sera displayed PRASTAT , 10% experienced significantly improved 1, 2, and 3 year graft survivals of 85% vs 73%, 83% vs 69%, and 82% vs 65% respectively, (P , .01 for each time point) compared to patients with pretransplant PRA–STAT $ reactivity. CONCLUSIONS
Delineation of HLA allosensitization and strong immune
CLARK, KERMAN, SUSSKIND ET AL
responder status may be important in identifying patients at risk for the occurrence of severe rejections.
REFERENCES 1. Kerman RH, Van Buren CT, Lewis RM, et al: Transplantation 49:52, 1990 2. Kerman RH, Susskind B, Buelow R, et al: Transplantation 62:201, 1996
P
RETRANSPLANT histocompatibility testing is done to select compatible donor-recipient pairs for renal allotransplantation. Sera from prospective transplant recipients are routinely screened for the presence of HLA antibodies to determine the extent of HLA alloimmuization. Highly reactive sera are tested against donor target cells to assess recipient-donor incompatibility. The standard technique to screen sera for anti-HLA antibodies utilizes an anti-human globulin enhanced cytotoxicity assay (AHG) wherein patient sera are tested against a panel of target lymphocytes of known HLA type, and the panel reactive antibody (PRA) is determined.1 The AHG-determined PRA does not always represent anti-HLA antibody reactivity and does not always correlate with posttransplant clinical events.2 Using a recently described ELISA procedure (PRA-STAT) to identify IgG and anti-HLA antibodies, we reported a significant correlation of PRA-STAT . 10% and the occurrence of posttransplant rejection episodes.2 The purpose of the present study was to correlate the severity of renal damage, assessed by Banff biopsy rejection grade, to the pretransplant state of HLA allosensitization.
MATERIALS AND METHODS Pretransplant sera from 207 cyclosporine-prednisone treated primary recipients of cadaveric renal allografts were studied. All donors and recipients were ABO compatible. HLA A, B, C, and DR tissue typing was performed as previously described.2 All recipients were transplanted following a negative pretransplant AHG crossmatch.1 ELISA-detected IgG anti-HLA % PRA was determined by using the PRA-STAT kit (SangStat Medical Corporation, Menlo Park, Calif.)2 Data were reported as PRASTAT $ 10% or PRA-STAT , 10%. The % PRA was correlated to the occurrence of rejection episodes during the first 12 months posttransplant and to the severity of renal damage, assessed by Banff biopsy rejection grade.
Table 2. Correlation of Pretransplant PRA-STAT and the Number of Rejections PRA-STAT
Rejections/Rejectors
,10%
$10%
1.2 1 0.8
2.1 1 0.71
P , .02.
RESULTS
Patients with PRA-STAT $ 10% (n 5 68) experienced a 50% rejection frequency compared with the 26% rejection frequency for patients with PRA-STAT , 10% (n 5 139), P , .001. Table 1. Moreover, rejecting patients with pretransplant PRA-STAT $ 10% experienced significantly more rejections (2.1 6 0.71 vs 1.2 6 0.8, P , .02) than did those patients with pretransplant PRA-STAT , 10%, Table 2. Of great interest was the fact that patients whose transplant sera displayed PRA-STAT $ 10% had more severe acute rejections (56% vs 14%, P , .001, Banff grade III) and fewer mild acute rejections (9% vs 67%, P , .001, Banff grade I) than patients with PRA-STAT , 10% sera, as shown in Table 3. Those patients experiencing rejections experienced a 26% frequency of biopsy proven chronic rejection in PRA-STAT $ 10% vs an 8% frequency of chronic rejection in PRA-STAT , 19% patients, P , .05.
Table 3. Pretransplant (PRA–STAT) Versus Posttransplant Banff Grade Rejections PRA-STAT
Acute Rejection Severe (B–III) Mild (B–I)I)
,10%
$10%
P
5 24
19 3
,.001 ,.001
Table 1. Correlation of Pretransplant PRA-STAT With Rejection During the First 12 Months Postoperatively PRA-STAT Rejection
Yes No
,10%
36 103
x2 5 11.8; P , .001.
© 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
$10%
34 34
From the Departments of Pathology and Surgery, Division of Organ Transplantation, The University of Texas Medical School, Houston, Texas, USA. Address reprint requests to Dr J. Clark, Department of Pathology, University of Texas Medical School, 6431 Fannin, MSB 2.252, Houston, Texas 77030. 0041-1345/99/$–see front matter PII S0041-1345(98)01755-2 751
Transplantation Proceedings, 31, 751–752 (1999)
752
Finally, patients whose pretransplant sera displayed PRASTAT , 10% experienced significantly improved 1, 2, and 3 year graft survivals of 85% vs 73%, 83% vs 69%, and 82% vs 65% respectively, (P , .01 for each time point) compared to patients with pretransplant PRA–STAT $ reactivity. CONCLUSIONS
Delineation of HLA allosensitization and strong immune
CLARK, KERMAN, SUSSKIND ET AL
responder status may be important in identifying patients at risk for the occurrence of severe rejections.
REFERENCES 1. Kerman RH, Van Buren CT, Lewis RM, et al: Transplantation 49:52, 1990 2. Kerman RH, Susskind B, Buelow R, et al: Transplantation 62:201, 1996