- Email: [email protected]
Impact of Positive Donor-Specific HLA Antibodies Crossmatch on Graft Survival in ABO-Incompatible Liver-Kidney Transplantation: A Case Report
Impact of Positive Donor-Specific HLA Antibodies Crossmatch on Graft Survival in ABO-Incompatible Liver-Kidney Transplantation: A Case Report C.-E. Hsieha, Y. Yangb, K.-H. Linc, C.-C. Chend, C.-J. Koc, Y.-L. Hsua, C.-C. Linc, Y.-J. Hungc, P.-Y. Line, S.-H. Wanga, and Y.-L. Chenb,f,* a Department of Liver Transplantation, Changhua Christian Hospital, Changhua; bDepartment of Nephrology, Changhua Christian Hospital; cGeneral Surgery, Changhua Christian Hospital, Changhua; dUrology Surgery, Changhua Christian Hospital, Changhua; e Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua; and fSchool of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
ABSTRACT We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibodymediated rejection did not occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from Tþ/Bþ to T-/Bþ. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days’ treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.
I
N patients with end-stage liver disease (ESLD) and endstage renal disease (ESRD), combined liver and kidney transplantation (CLKT) is usually recommended. Recipients who have undergone ABO-incompatible (ABOi) adult living-donor liver transplantation (LDLT) have been shown to have good survival outcomes. The 3-year liver graft and patient survival rates in an ABOi group were 89.2% and 92.3%, respectively [1]. The survival outcomes of recipients who have undergone ABOi adult living-donor renal transplantation (LDRT) are also generally good; he 9-year renal graft and patient survival rates of an ABOi group were 86.9% and 96.7%, respectively [2]. Potential live kidney donors are commonly prohibited from donating if their prospective recipients have preformed donor-specific antibody (DSA) detected by current crossmatching techniques or due to blood type incompatibility. To the best of our knowledge, positive DSA and crossmatch in ABOi 0041-1345/18 https://doi.org/10.1016/j.transproceed.2018.05.018
4008
combined liver-kidney transplantation has not been reported. We present a patient with simultaneous ABO and crossmatch incompatibilities who underwent a successful CLKT following preoperative intervention. The patient’s grafts have survived for over a year at the time of writing. CASE REPORT A 56-year-old man (blood group O; HLA A11,33; B13,58; C 3, 07; DR 3,12; DQ 2,3; donor-specific antibodies A1, A24, A23, anti-B antibody titer IgG 1:512) with a history of hepatitis B virusrelated liver cirrhosis (Model for End-Stage Liver Disease score
*Address correspondence to Yao-Li Chen, Department of General Surgery, Changhua Christian Hospital, No. 135 NanHsiao Street, Changhua, Taiwan. Tel: þ886-4-7238595; Fax: þ886-4-7232942. E-mail: [email protected] ª 2018 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 50, 4008e4011 (2018)
POSITIVE DSA IN ABOI LIVER-KIDNEY TRANSPLANT
4009
24) and chronic renal failure underwent an adult CLKT. We performed laboratory tests, including heart, lung, liver, and renal function tests. Abdominal computed tomography was performed to assess liver and renal vascular anatomy and liver volume, and magnetic resonance cholangiopancreatography was performed to evaluate biliary anatomy in all potential donors, including his 52-year-old wife and 28-year-old son. We found elevated liver function parameters in the patient’s son, indicating severe fatty liver and hepatitis, so he was rejected as a liver donor. The patient’s son (blood group B; HLA A24,33; B54,58; C 1, 3; DR 3,4; DQ 2,4) and wife (blood group B; HLA A2, 24; B 37,54; C 1, 6; DR 4,10; DQ 4, 5) had the donor-specific antibody A24. The patient had received transfusion before transplantation. The relative strengths for the HLA antibodies of wife and son were shown as A24 (8139.46) of the mean fluorescence intensity (MFI). HLA specificities were determined by using LABScreen Single Antigen HLA Class I-Combi and LABScreen Single Antigen Class II Antibody Detection reagent kits (One Lambda, Thermo Fisher Scientific, Canoga Park, Calif, United States), which are designed to identify the specificity of HLA Class I and Class II antibodies. MFI values greater than or equal to 2000 were chosen as the cutoff point for determining clinical importance [3]. Complement-dependent cytotoxicity (CDC) and flow cytometry cross-match (FCXM) were performed and the results were positive for T lymphocytes and strongly positive for B lymphocytes. The recipient had been diagnosed with a soft tumor measuring 2.3 1.5 1.5 cm at the surface of S6 by computed tomography, so the recipient’s son was considered the most suitable for renal donation while his wife was deemed to be a candidate for liver donation. The preoperative protocol for ABOi consisted of a single dose of rituximab (375 mg/m2 per body surface area) before preoperative day 21 and total plasma exchange (TPE). The first pretransplant TPE was performed 1e2 weeks after administration. The target of anti-B antibody titer became IgG 1:32 and renal donor and recipient of crossmatch results shown desensitization level. The MFI value of the DSA anti-A24 was 8139.46 and 2438.4 before and after desensitization, respectively. The results of FCXM revealed a change from Tþ/Bþ to T-/Bþ and the MFI ratio of FCXM T/B lymphocytes decreased (Table 1). The recipient required adult living-donor CLKT. The timing
depended on the recipient’s isoagglutinin titer, CDC, and FCXM after TPE. Our intra and post-operative protocol included intravenous basiliximab, no splenectomy, no local graft infusion administered through either the hepatic artery or portal vein, and a systemic triple immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone. The last time dose of rituximab (150 mg/m2 per body surface area) was infused on postoperative day 1. After transplantation, anti-B antibody titer IgG was monitored frequently every day (except Sunday) in the first 2 weeks, and immunosuppression with tacrolimus trough levels were maintained at around 9e15 ng/mL, and mycophenolate mofetil (2 g/day) was initiated. Corticosteroid was tapered off over 3 months after transplantation. On post-transplantation day 10, the patient’s creatinine was found to have increased up to 2.48 mg/dL, and acute rejection episodes were suspected, so we administered rabbit antithymocyte globulin (ATG) 1 mg/kg/day (7 times), which appeared to decrease the creatinine level to within the normal range(Fig 1). On post-transplantation day 18, the patient had fever and chills. His blood culture revealed Acinetobacter baumannii complex, which we treated with an antibiotic for 14 days. The patient’s renal and liver functions stabilized and he was discharged shortly afterward (Fig 1). At 13 months post-transplantation, the patient’s alanine aminotransferase level was 30 U/L and the creatinine level was 1.08 mg/dL. The study was approved by the Institutional Review Board of the Changhua Christian Hospital (No. CCH 170810).
DISCUSSION
CLKT is a mature discipline and is the standard of care for cases with both ESLD and ESRD. The procedure for ABOi living liver or renal donor is a safe method for expanding the donor pool for transplantation. The use of rituximab and TPE has dramatically improved the outcome of adult ABOi transplantation [1,2,4,5]. Following the introduction of the anti-CD20 monoclonal antibody rituximab and plasma exchange, there is little risk of developing hepatic necrosis-
Table 1. Following Treatment With Rituximab and Total Plasma Exchange, Donor-Specific Antibody Crossmatch and Isoagglutinin Titer Were Detected Before Transplant Baseline
Anti-B antibody IgG titer CDC T cell
FCXM
512
37 C Weak positive 4 C Positive B cell 37 C Strongly positive 4 C Strongly positive T cell Negative control 0.327 MFI Patient MFI 0.803 MFI ratio 2.46 Result Positive B cell Negative control 0.318 MFI Patient MFI 1.52 MFI ratio 4.78 Result Positive
TPE 1 (-11 day) TPE 2 (-9 day)
32
32
TPE 3 (-7 day)
TPE 4 (-4 day)
TPE 5 (-2 day)
16
16
32
Negative Negative Strongly positive Strongly positive 0.327
Negative Negative Strongly positive Strongly positive 0.321
0.333 1.02 Positive 0.342
0.324 1 Negative 0.345
28.6 83.6 Positive
16.9 49 Positive
Abbreviations: CDC, complement-dependent cytotoxicity; FCXM, flow cytometry cross-match; MFI, mean fluorescence intensity; TPE, total plasma exchange.
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HSIEH, YANG, LIN ET AL
Fig 1. Liver and renal function data and isoagglutinin titer post-ABO-incompatible combined liver and kidney transplantation. Abbreviations: ALT, alanine aminotransferase; Bil T, total bilirubin; Cr, creatinine; POD, postoperative day.
induced antibody-mediated rejection (AMR). Due to the insufficient numbers of pronase-treated B cells recruited, the B-CDC crossmatch with pronase-treated B cell was not performed in this study. The false positive B cell crossmatch related to rituximab use cannot be ruled out. Although CDC and FCXM B lymphocytes were strongly positive, it has been reported that a positive CDC result may be interpreted as a
false positive caused by rituximab-induced B-cell lysis [6,7]. The results of the crossmatch showed desensitization after plasma exchange in both kidney donor and recipient prior to transplantation. The MFI ratio of FCXM T/B lymphocytes decreased, which may suggest living donor transplantation. Neumann et al. found that positive crossmatch used for CLKT affords protection against alloantibody and humoral
POSITIVE DSA IN ABOI LIVER-KIDNEY TRANSPLANT
rejection [8]. The liver and renal function of results were recovery after transplantation. Crossmatch results after transplantation have not been measured. On posttransplantation day 10, an anti-B antibody titer IgG was only 1:2 and the patient’s creatinine level increased to 2.48 mg/dL, so acute rejection episodes were suspected. We could not diagnose antibody-mediated rejection or acute cellular rejection by renal biopsy. Treatment with ATG downregulates the expression of several molecules that control T-cell activation, and strongly induces apoptosis in vitro against naive, activated B cells or bone marrow resident plasma cells. Thymoglobulin is used for treatment of acute rejection, especially steroid-resistant and antibodymediated rejection. We have used thymoglobulin to treat acute rejection and successfully prevented acute rejection episodes for 7 days [9,10]. Other strategies with intravenous immunoglobulin (IVIG) could be effective options [11,12]. The mechanisms of action include inhibition of CD19 expression in activated B cells, inhibition of complement, and inhibition of alloreactive T cells. However, crossmatch results (DSA and/or FCXM) after transplantation have not been measured. In our case, biochemical markers of liver and renal function were evaluated during follow up period and the results were normal. Positive DSA, CDC, and FCXM crossmatches predicted higher incidence of acute rejection episodes or antibodymediated rejection (AMR) [13]. Antibody detection and analysis are thus essential for predicting post-transplant immunological complications. In one study, the rate of chronic AMR was 39.5% in first year, and allograft survival rates at 1, 5, and 7 years were 98%, 86%, and 78%, respectively [14]. Post-transplant immunosuppressive therapy included tacrolimus (9e15 ng/mL) and mycophenolate mofetil (1.5 g/day), and we ceased clinical and immunologic monitoring. We expect that long term follow up is needed. In conclusion, DSA, CDC, and FCXM crossmatches are known to increase the risk of graft rejection and therefore it is vital to perform antibody detection and related analyses. In the rituximab era, TPE can achieve a successful decrease of antibody titer. In Taiwan, most transplants have been performed using living donors because of the severe shortage of cadaveric organ donors. Our findings
4011
demonstrate that DSA/crossmatch positive and ABOi individuals could still be organ donor candidates. ACKNOWLEDGMENT The authors would like to thank the department of laboratory medicine in Changhua Christian Hospital.
REFERENCES [1] Song GW, Lee SG, Hwang S, et al. ABO-incompatible adult living donor liver transplantation under the desensitization protocol with rituximab. Am J Transplant 2016;16:157e70. [2] Okumi M, Toki D, Nozaki T, et al. ABO-incompatible living kidney transplants: evolution of outcomes and immunosuppressive management. Am J Transplant 2016;16:886e96. [3] Slavcev A. Donor-specific antibodies and kidney transplant rejection. Ann Transplant 2003;8:12e5. [4] Billen EV, Christiaans MH, Lee J, et al. Donor-directed HLA antibodies before and after transplantectomy detected by the luminex single antigen assay. Transplantation 2009;87:563e9. [5] Lee CF, Cheng CH, Wang YC, et al. Adult living donor liver transplantation across ABO-incompatibility. Medicine (Baltimore) 2015;94:e1796. [6] Reindl-Schwaighofer R, Oberbauer R. False-positive CDC x-match after rituximab. Transpl Int 2014;27:e124e5. [7] Desoutter J, Apithy MJ, Bartczak S, et al. False positive Bcells crossmatch after prior rituximab exposure of the kidney donor. Case Rep Transplant 2016:4534898. [8] Neumann UP, Lang M, Moldenhauer A, et al. Significance of a T-lymphocytotoxic crossmatch in liver and combined liver-kidney transplantation. Transplantation 2001;71:1163e8. [9] de Castro MC, Deboni L, Esmeraldo Rde M, et al. Use of Thymoglobulin (antithymocyte immunoglobulin) in renal transplantation: practical guide. J Bras Nefrol 2015;37:228e40. [10] Thiyagarajan UM, Ponnuswamy A, Bagul A. Thymoglobulin and its use in renal transplantation: a review. Am J Nephrol 2013;37:586e601. [11] Urbani L, Mazzoni A, Bianco I, et al. The role of immunomodulation in ABO-incompatible adult liver transplant recipients. J Clin Apher 2008;23:55e62. [12] Garces JC, Giusti S, Staffeld-Coit C, et al. Antibody-mediated rejection: a review. Ochsner J 2017;17:46e55. [13] Lo P, Sharma A, Craig JC, et al. Preconditioning therapy in ABO-incompatible living kidney transplantation: a systematic review and meta-analysis. Transplantation 2016;100:933e42. [14] Amrouche L, Aubert O, Suberbielle C, et al. Long-term outcomes of kidney transplantation in patients with high levels of preformed DSA: the Necker High-Risk Transplant Program. Transplantation 2017;101:2440e8.
ABSTRACT We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibodymediated rejection did not occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from Tþ/Bþ to T-/Bþ. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days’ treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.
I
N patients with end-stage liver disease (ESLD) and endstage renal disease (ESRD), combined liver and kidney transplantation (CLKT) is usually recommended. Recipients who have undergone ABO-incompatible (ABOi) adult living-donor liver transplantation (LDLT) have been shown to have good survival outcomes. The 3-year liver graft and patient survival rates in an ABOi group were 89.2% and 92.3%, respectively [1]. The survival outcomes of recipients who have undergone ABOi adult living-donor renal transplantation (LDRT) are also generally good; he 9-year renal graft and patient survival rates of an ABOi group were 86.9% and 96.7%, respectively [2]. Potential live kidney donors are commonly prohibited from donating if their prospective recipients have preformed donor-specific antibody (DSA) detected by current crossmatching techniques or due to blood type incompatibility. To the best of our knowledge, positive DSA and crossmatch in ABOi 0041-1345/18 https://doi.org/10.1016/j.transproceed.2018.05.018
4008
combined liver-kidney transplantation has not been reported. We present a patient with simultaneous ABO and crossmatch incompatibilities who underwent a successful CLKT following preoperative intervention. The patient’s grafts have survived for over a year at the time of writing. CASE REPORT A 56-year-old man (blood group O; HLA A11,33; B13,58; C 3, 07; DR 3,12; DQ 2,3; donor-specific antibodies A1, A24, A23, anti-B antibody titer IgG 1:512) with a history of hepatitis B virusrelated liver cirrhosis (Model for End-Stage Liver Disease score
*Address correspondence to Yao-Li Chen, Department of General Surgery, Changhua Christian Hospital, No. 135 NanHsiao Street, Changhua, Taiwan. Tel: þ886-4-7238595; Fax: þ886-4-7232942. E-mail: [email protected] ª 2018 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 50, 4008e4011 (2018)
POSITIVE DSA IN ABOI LIVER-KIDNEY TRANSPLANT
4009
24) and chronic renal failure underwent an adult CLKT. We performed laboratory tests, including heart, lung, liver, and renal function tests. Abdominal computed tomography was performed to assess liver and renal vascular anatomy and liver volume, and magnetic resonance cholangiopancreatography was performed to evaluate biliary anatomy in all potential donors, including his 52-year-old wife and 28-year-old son. We found elevated liver function parameters in the patient’s son, indicating severe fatty liver and hepatitis, so he was rejected as a liver donor. The patient’s son (blood group B; HLA A24,33; B54,58; C 1, 3; DR 3,4; DQ 2,4) and wife (blood group B; HLA A2, 24; B 37,54; C 1, 6; DR 4,10; DQ 4, 5) had the donor-specific antibody A24. The patient had received transfusion before transplantation. The relative strengths for the HLA antibodies of wife and son were shown as A24 (8139.46) of the mean fluorescence intensity (MFI). HLA specificities were determined by using LABScreen Single Antigen HLA Class I-Combi and LABScreen Single Antigen Class II Antibody Detection reagent kits (One Lambda, Thermo Fisher Scientific, Canoga Park, Calif, United States), which are designed to identify the specificity of HLA Class I and Class II antibodies. MFI values greater than or equal to 2000 were chosen as the cutoff point for determining clinical importance [3]. Complement-dependent cytotoxicity (CDC) and flow cytometry cross-match (FCXM) were performed and the results were positive for T lymphocytes and strongly positive for B lymphocytes. The recipient had been diagnosed with a soft tumor measuring 2.3 1.5 1.5 cm at the surface of S6 by computed tomography, so the recipient’s son was considered the most suitable for renal donation while his wife was deemed to be a candidate for liver donation. The preoperative protocol for ABOi consisted of a single dose of rituximab (375 mg/m2 per body surface area) before preoperative day 21 and total plasma exchange (TPE). The first pretransplant TPE was performed 1e2 weeks after administration. The target of anti-B antibody titer became IgG 1:32 and renal donor and recipient of crossmatch results shown desensitization level. The MFI value of the DSA anti-A24 was 8139.46 and 2438.4 before and after desensitization, respectively. The results of FCXM revealed a change from Tþ/Bþ to T-/Bþ and the MFI ratio of FCXM T/B lymphocytes decreased (Table 1). The recipient required adult living-donor CLKT. The timing
depended on the recipient’s isoagglutinin titer, CDC, and FCXM after TPE. Our intra and post-operative protocol included intravenous basiliximab, no splenectomy, no local graft infusion administered through either the hepatic artery or portal vein, and a systemic triple immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone. The last time dose of rituximab (150 mg/m2 per body surface area) was infused on postoperative day 1. After transplantation, anti-B antibody titer IgG was monitored frequently every day (except Sunday) in the first 2 weeks, and immunosuppression with tacrolimus trough levels were maintained at around 9e15 ng/mL, and mycophenolate mofetil (2 g/day) was initiated. Corticosteroid was tapered off over 3 months after transplantation. On post-transplantation day 10, the patient’s creatinine was found to have increased up to 2.48 mg/dL, and acute rejection episodes were suspected, so we administered rabbit antithymocyte globulin (ATG) 1 mg/kg/day (7 times), which appeared to decrease the creatinine level to within the normal range(Fig 1). On post-transplantation day 18, the patient had fever and chills. His blood culture revealed Acinetobacter baumannii complex, which we treated with an antibiotic for 14 days. The patient’s renal and liver functions stabilized and he was discharged shortly afterward (Fig 1). At 13 months post-transplantation, the patient’s alanine aminotransferase level was 30 U/L and the creatinine level was 1.08 mg/dL. The study was approved by the Institutional Review Board of the Changhua Christian Hospital (No. CCH 170810).
DISCUSSION
CLKT is a mature discipline and is the standard of care for cases with both ESLD and ESRD. The procedure for ABOi living liver or renal donor is a safe method for expanding the donor pool for transplantation. The use of rituximab and TPE has dramatically improved the outcome of adult ABOi transplantation [1,2,4,5]. Following the introduction of the anti-CD20 monoclonal antibody rituximab and plasma exchange, there is little risk of developing hepatic necrosis-
Table 1. Following Treatment With Rituximab and Total Plasma Exchange, Donor-Specific Antibody Crossmatch and Isoagglutinin Titer Were Detected Before Transplant Baseline
Anti-B antibody IgG titer CDC T cell
FCXM
512
37 C Weak positive 4 C Positive B cell 37 C Strongly positive 4 C Strongly positive T cell Negative control 0.327 MFI Patient MFI 0.803 MFI ratio 2.46 Result Positive B cell Negative control 0.318 MFI Patient MFI 1.52 MFI ratio 4.78 Result Positive
TPE 1 (-11 day) TPE 2 (-9 day)
32
32
TPE 3 (-7 day)
TPE 4 (-4 day)
TPE 5 (-2 day)
16
16
32
Negative Negative Strongly positive Strongly positive 0.327
Negative Negative Strongly positive Strongly positive 0.321
0.333 1.02 Positive 0.342
0.324 1 Negative 0.345
28.6 83.6 Positive
16.9 49 Positive
Abbreviations: CDC, complement-dependent cytotoxicity; FCXM, flow cytometry cross-match; MFI, mean fluorescence intensity; TPE, total plasma exchange.
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HSIEH, YANG, LIN ET AL
Fig 1. Liver and renal function data and isoagglutinin titer post-ABO-incompatible combined liver and kidney transplantation. Abbreviations: ALT, alanine aminotransferase; Bil T, total bilirubin; Cr, creatinine; POD, postoperative day.
induced antibody-mediated rejection (AMR). Due to the insufficient numbers of pronase-treated B cells recruited, the B-CDC crossmatch with pronase-treated B cell was not performed in this study. The false positive B cell crossmatch related to rituximab use cannot be ruled out. Although CDC and FCXM B lymphocytes were strongly positive, it has been reported that a positive CDC result may be interpreted as a
false positive caused by rituximab-induced B-cell lysis [6,7]. The results of the crossmatch showed desensitization after plasma exchange in both kidney donor and recipient prior to transplantation. The MFI ratio of FCXM T/B lymphocytes decreased, which may suggest living donor transplantation. Neumann et al. found that positive crossmatch used for CLKT affords protection against alloantibody and humoral
POSITIVE DSA IN ABOI LIVER-KIDNEY TRANSPLANT
rejection [8]. The liver and renal function of results were recovery after transplantation. Crossmatch results after transplantation have not been measured. On posttransplantation day 10, an anti-B antibody titer IgG was only 1:2 and the patient’s creatinine level increased to 2.48 mg/dL, so acute rejection episodes were suspected. We could not diagnose antibody-mediated rejection or acute cellular rejection by renal biopsy. Treatment with ATG downregulates the expression of several molecules that control T-cell activation, and strongly induces apoptosis in vitro against naive, activated B cells or bone marrow resident plasma cells. Thymoglobulin is used for treatment of acute rejection, especially steroid-resistant and antibodymediated rejection. We have used thymoglobulin to treat acute rejection and successfully prevented acute rejection episodes for 7 days [9,10]. Other strategies with intravenous immunoglobulin (IVIG) could be effective options [11,12]. The mechanisms of action include inhibition of CD19 expression in activated B cells, inhibition of complement, and inhibition of alloreactive T cells. However, crossmatch results (DSA and/or FCXM) after transplantation have not been measured. In our case, biochemical markers of liver and renal function were evaluated during follow up period and the results were normal. Positive DSA, CDC, and FCXM crossmatches predicted higher incidence of acute rejection episodes or antibodymediated rejection (AMR) [13]. Antibody detection and analysis are thus essential for predicting post-transplant immunological complications. In one study, the rate of chronic AMR was 39.5% in first year, and allograft survival rates at 1, 5, and 7 years were 98%, 86%, and 78%, respectively [14]. Post-transplant immunosuppressive therapy included tacrolimus (9e15 ng/mL) and mycophenolate mofetil (1.5 g/day), and we ceased clinical and immunologic monitoring. We expect that long term follow up is needed. In conclusion, DSA, CDC, and FCXM crossmatches are known to increase the risk of graft rejection and therefore it is vital to perform antibody detection and related analyses. In the rituximab era, TPE can achieve a successful decrease of antibody titer. In Taiwan, most transplants have been performed using living donors because of the severe shortage of cadaveric organ donors. Our findings
4011
demonstrate that DSA/crossmatch positive and ABOi individuals could still be organ donor candidates. ACKNOWLEDGMENT The authors would like to thank the department of laboratory medicine in Changhua Christian Hospital.
REFERENCES [1] Song GW, Lee SG, Hwang S, et al. ABO-incompatible adult living donor liver transplantation under the desensitization protocol with rituximab. Am J Transplant 2016;16:157e70. [2] Okumi M, Toki D, Nozaki T, et al. ABO-incompatible living kidney transplants: evolution of outcomes and immunosuppressive management. Am J Transplant 2016;16:886e96. [3] Slavcev A. Donor-specific antibodies and kidney transplant rejection. Ann Transplant 2003;8:12e5. [4] Billen EV, Christiaans MH, Lee J, et al. Donor-directed HLA antibodies before and after transplantectomy detected by the luminex single antigen assay. Transplantation 2009;87:563e9. [5] Lee CF, Cheng CH, Wang YC, et al. Adult living donor liver transplantation across ABO-incompatibility. Medicine (Baltimore) 2015;94:e1796. [6] Reindl-Schwaighofer R, Oberbauer R. False-positive CDC x-match after rituximab. Transpl Int 2014;27:e124e5. [7] Desoutter J, Apithy MJ, Bartczak S, et al. False positive Bcells crossmatch after prior rituximab exposure of the kidney donor. Case Rep Transplant 2016:4534898. [8] Neumann UP, Lang M, Moldenhauer A, et al. Significance of a T-lymphocytotoxic crossmatch in liver and combined liver-kidney transplantation. Transplantation 2001;71:1163e8. [9] de Castro MC, Deboni L, Esmeraldo Rde M, et al. Use of Thymoglobulin (antithymocyte immunoglobulin) in renal transplantation: practical guide. J Bras Nefrol 2015;37:228e40. [10] Thiyagarajan UM, Ponnuswamy A, Bagul A. Thymoglobulin and its use in renal transplantation: a review. Am J Nephrol 2013;37:586e601. [11] Urbani L, Mazzoni A, Bianco I, et al. The role of immunomodulation in ABO-incompatible adult liver transplant recipients. J Clin Apher 2008;23:55e62. [12] Garces JC, Giusti S, Staffeld-Coit C, et al. Antibody-mediated rejection: a review. Ochsner J 2017;17:46e55. [13] Lo P, Sharma A, Craig JC, et al. Preconditioning therapy in ABO-incompatible living kidney transplantation: a systematic review and meta-analysis. Transplantation 2016;100:933e42. [14] Amrouche L, Aubert O, Suberbielle C, et al. Long-term outcomes of kidney transplantation in patients with high levels of preformed DSA: the Necker High-Risk Transplant Program. Transplantation 2017;101:2440e8.