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Influence of pretransplant allosensitization in cardiac transplant outcome
Influence of Pretransplant Allosensitization in Cardiac Transplant Outcome F. Monteiro, H. Rodrigues, C. Viggiani, A. Fiorelli, N. Stolf, and J. Kalil
T
HE PRESENCEof pretransplant circulating antibodies (allosensitization) could reflect a state of enhanced overall immune reactivity. Although this risk factor is well established for renal transplantation, the effect of pretransplant sensitization on the outcome of cardiac transplant has been controversial. In the current study, the importance of preformed antibodies against T lymphocytes in the panel reactive antibody (PRA) screening is evaluated.
Table 1. Three-Year Survival for T-Lymphocyte Panel Reactive Antibodies AGH T-Cell Panel Reactive Antibodies Year Post-TX
1 2 3*
⬍10% (n ⫽ 93)
⬎10% (n ⫽ 3)
60 58 58
33 33 0
*P ⬍ .05
MATERIALS AND METHODS Patients This study retrospectively reviewed 96 patients who underwent cardiac transplant at our institution between March 1989 and October 1996. All patients were transplanted against a negative donor-specific crossmatch at the time of transplant. There were 75 males and 21 females from different ethnic groups. The mean patient age was 30; the median age was 29. Immunosuppressive therapy consisted of classic triple therapy, and rejection episodes were biopsy proven.
PRA Screen The PRA screen was performed by lymphocytotoxicity technique (anti-human globulin protocol). The recipient sera were tested against a panel with 30 T cell well matched with the frequency of HLA antigens displayed in our population. To remove immunoglobin M (IgM) antibodies, the recipient sera were also treated with dithiothreitol (DTT). Recipient sera reacting with 10% or more of the panel cells were considered positive.
Statistical Analysis Statistical comparisons were performed by Student’s t test, and Kaplan-Meier curve was analyzed by log-rank statistics.
RESULTS
The demographics of the two groups, positive (n ⫽ 3) and negative (n ⫽ 93) PRA were not significantly different. The presence of antibodies detected in the pretransplant serum specimen showed mean of %PRA values significantly higher (P ⬍ .003) in the three patients with T cell PRA ⬎ 10% (38 ⫾ 40%) compared to patients with PRA ⱕ 10% (1 ⫾ 3.2%). Also, as shown in Table 1, patients with T-cell PRA ⬎ 10% had lower 3-year survival (three deaths of three) than those patients with PRA ⱕ 10%, (39 of 93) (P ⬍ .05). Moreover, two of three deaths (67%) in patient group 0041-1345/99/$–see front matter PII S0041-1345(99)00637-5 2988
with PRA ⬎ 10% occurred within 60 days after transplant. Finally, the average of rejection episodes was similar between patients with PRA ⱕ 10% (.0 ⫾ 1.0) and patients with PRA ⬎ 10% (1.0 ⫾ 1.5). DISCUSSION
The current study shows that pretransplant monitoring of IgG anti-T-cell antibodies detection may indicate high-risk heart transplant patients. While our data are consistent with previous reports from Kobashigawa et al1 and Loh et al2 studies, McCloskey et al3 and Opelz et al4 did not find any correlation between graft heart transplant survival and %PRA value. These discrepant results could be because the antibody target as well as the immunoglobulin isotype antibody are not well characterized in those articles.3,4 REFERENCES 1. Kobashigawa AJ, Sabad A, Drinkwater D, et al: Circulation 94:294, 1996 2. Loh E, Bergin JD, Couper GS, et al: J Heart Lung Transplant 13:194, 1994 3. McCloskey D, Festenstein H, Banner N, et al: Transplant Proc 21:804, 1989 4. Opelz G, Reichert B, Mollner H: In Thompson ME (ed): Cardiac Transplantation. Philadelphia: F A Davis Co: 1990, p 91 From the Laboratory of Transplantation Immunology (F.M., H.R., C.V., J.K.) Allergy and Clinical Immunology (J.K.), Department of Clinical Mecicine and Surgery Division (A.F., N.S.), Heart Institute (InCor), University of Sa˜o Paulo, Medical School, Sa˜o Paulo, Brazil. J.K. is an International Scholar Howard Hughes. Address reprint requests to Francisco Monteiro, Laborato´rio de imunologia de Transplantes, Instituto do corac¸a˜o, Faculdade de Medicina, Universidade de sa˜o Paulo Rua Dr Eneas de Carvalho Aguiar 500, 3 o andar, 05403-000, Sa˜o Paulo, SP, Brazil. © 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 31, 2988 (1999)
T
HE PRESENCEof pretransplant circulating antibodies (allosensitization) could reflect a state of enhanced overall immune reactivity. Although this risk factor is well established for renal transplantation, the effect of pretransplant sensitization on the outcome of cardiac transplant has been controversial. In the current study, the importance of preformed antibodies against T lymphocytes in the panel reactive antibody (PRA) screening is evaluated.
Table 1. Three-Year Survival for T-Lymphocyte Panel Reactive Antibodies AGH T-Cell Panel Reactive Antibodies Year Post-TX
1 2 3*
⬍10% (n ⫽ 93)
⬎10% (n ⫽ 3)
60 58 58
33 33 0
*P ⬍ .05
MATERIALS AND METHODS Patients This study retrospectively reviewed 96 patients who underwent cardiac transplant at our institution between March 1989 and October 1996. All patients were transplanted against a negative donor-specific crossmatch at the time of transplant. There were 75 males and 21 females from different ethnic groups. The mean patient age was 30; the median age was 29. Immunosuppressive therapy consisted of classic triple therapy, and rejection episodes were biopsy proven.
PRA Screen The PRA screen was performed by lymphocytotoxicity technique (anti-human globulin protocol). The recipient sera were tested against a panel with 30 T cell well matched with the frequency of HLA antigens displayed in our population. To remove immunoglobin M (IgM) antibodies, the recipient sera were also treated with dithiothreitol (DTT). Recipient sera reacting with 10% or more of the panel cells were considered positive.
Statistical Analysis Statistical comparisons were performed by Student’s t test, and Kaplan-Meier curve was analyzed by log-rank statistics.
RESULTS
The demographics of the two groups, positive (n ⫽ 3) and negative (n ⫽ 93) PRA were not significantly different. The presence of antibodies detected in the pretransplant serum specimen showed mean of %PRA values significantly higher (P ⬍ .003) in the three patients with T cell PRA ⬎ 10% (38 ⫾ 40%) compared to patients with PRA ⱕ 10% (1 ⫾ 3.2%). Also, as shown in Table 1, patients with T-cell PRA ⬎ 10% had lower 3-year survival (three deaths of three) than those patients with PRA ⱕ 10%, (39 of 93) (P ⬍ .05). Moreover, two of three deaths (67%) in patient group 0041-1345/99/$–see front matter PII S0041-1345(99)00637-5 2988
with PRA ⬎ 10% occurred within 60 days after transplant. Finally, the average of rejection episodes was similar between patients with PRA ⱕ 10% (.0 ⫾ 1.0) and patients with PRA ⬎ 10% (1.0 ⫾ 1.5). DISCUSSION
The current study shows that pretransplant monitoring of IgG anti-T-cell antibodies detection may indicate high-risk heart transplant patients. While our data are consistent with previous reports from Kobashigawa et al1 and Loh et al2 studies, McCloskey et al3 and Opelz et al4 did not find any correlation between graft heart transplant survival and %PRA value. These discrepant results could be because the antibody target as well as the immunoglobulin isotype antibody are not well characterized in those articles.3,4 REFERENCES 1. Kobashigawa AJ, Sabad A, Drinkwater D, et al: Circulation 94:294, 1996 2. Loh E, Bergin JD, Couper GS, et al: J Heart Lung Transplant 13:194, 1994 3. McCloskey D, Festenstein H, Banner N, et al: Transplant Proc 21:804, 1989 4. Opelz G, Reichert B, Mollner H: In Thompson ME (ed): Cardiac Transplantation. Philadelphia: F A Davis Co: 1990, p 91 From the Laboratory of Transplantation Immunology (F.M., H.R., C.V., J.K.) Allergy and Clinical Immunology (J.K.), Department of Clinical Mecicine and Surgery Division (A.F., N.S.), Heart Institute (InCor), University of Sa˜o Paulo, Medical School, Sa˜o Paulo, Brazil. J.K. is an International Scholar Howard Hughes. Address reprint requests to Francisco Monteiro, Laborato´rio de imunologia de Transplantes, Instituto do corac¸a˜o, Faculdade de Medicina, Universidade de sa˜o Paulo Rua Dr Eneas de Carvalho Aguiar 500, 3 o andar, 05403-000, Sa˜o Paulo, SP, Brazil. © 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 31, 2988 (1999)