ORIGINAL ARTICLE pISSN 2288-6575 • eISSN 2288-6796 http://dx.doi.org/10.4174/astr.2015.88.2.100 Annals of Surgical Treatment and Research
Effect of donor-specific antibodies and panel reactive antibodies in living donor liver transplant recipients Seung Hwan Song1, Myoung Soo Kim1,2, Jung Jun Lee3, Man Ki Ju1,2, Jae Geun Lee1,2, Juhan Lee1,2, Jin Sub Choi1,2, Gi Hong Choi1,2, Soon Il Kim1,2, Dong Jin Joo1,2 Department of Surgery and 2The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea
1 3
Purpose: Preformed circulating donor-specific antibodies (DSAs) immunologically challenge vascular endothelium and the bile duct. However, the liver is an immune-tolerant organ and can avoid immunological challenges. This study was undertaken to analyze the effects of DSAs after adult living donor liver transplantation (LDLT). Methods: We retrospectively reviewed 219 LDLT patients’ records treated at our center. Results: Of the 219 patients, 32 (14.6%) were DSA (+) and 187 (85.4%) were DSA (–). Class I DSAs were present in 18 patients, class II in seven patients, and both in seven patients. Seven patients (3.2%) showed DSA to HLA-A, four (1.8%) to HLA-B, seven (3.2%) to HLA-DR, and 14 (6.4%) to two or more HLAs. More DSAs were observed in female recipients than male recipients in the DSA (+) group. The DSA (+) group showed significantly higher levels of class I and II panel reactive antibody (PRA) than did the DSA (–) group. No significant intergroup differences were found between incidences of primary nonfunction, acute rejection, vascular complication, or biliary complication. There were no significant differences in graft survival rates between the two groups. However, the recipients with multiple DSAs tended to have more acute rejection episodes and events of biliary stricture and lower graft survival rates than did patients in the DSA (–) group. Conclusion: In LDLT, the presence of multiple DSAs and high PRA seemed to be associated with poor graft outcomes, although our results did not reach statistical significance. Large cohort studies are necessary to clarify the impact of DSA and PRA in LDLT. [Ann Surg Treat Res 2015;88(2):100-105] Key Words: Liver transplantation, Donor specific antibody, Acute rejection, Graft survival, Sensitization
INTRODUCTION Highly sensitized organ recipients are at greater risk of acute rejection, vascular complications, and poor graft survival [1-3]. Circulating donor-specific antibodies (DSAs) immunologically challenge the vascular endothelium and bile duct [4], but the liver is uniquely able to neutralize antibodies and escape from immunologic challenges [5,6]. However, the effects of DSAs on graft function and survival after liver transplantation remains controversial. Some authors suggest that a positive T lymphocyte cross match results in poor graft survival and more
Received June 19, 2014, Revised August 5, 2014, Accepted August 14, 2014 Corresponding Author: Dong Jin Joo Department of Surgery, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea Tel: +82-2-2228-2131, Fax: +82-2-313-8289 E-mail: [email protected]
100
acute rejection [7,8], whereas others conclude that a positive T lymphocyte cross match has no effect on graft outcome [9,10]. Additionally, the role of circulating preformed DSAs before liver transplantation is unclear. Consequently, the aim of this study was to determine if preformed circulating DSAs negatively affect graft outcome after living donor liver transplantation (LDLT).
METHODS The medical records of 219 adult LDLT patients that un
Copyright ⓒ 2015, the Korean Surgical Society cc Annals of Surgical Treatment and Research is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution NonCommercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Seung Hwan Song, et al: Effect of DSA and PRA in LDLT
derwent treatment at Yonsei University College of Medicine between June 2006 and August 2012 were retrospectively reviewed. Pediatric and second transplant cases were excluded. Patients were allocated to two groups according to the presence of DSA. DSAs were identified by panel reactive antibody (PRA) identification conducted by ELISA using the Lambda Cell Tray lymphocytotoxicity assay (One Lambda Inc., Canoga Park, CA, USA). Records were reviewed for clinical and immunological characteristics, acute rejection episodes, complications, and graft survival. The primary immunosuppressive therapy used posttrans plant was a tacrolimus-based agent. Induction therapy with interleukin-2 receptor antibody (basiliximab) was used, except in cases with identical HLA matching. Antimetabolite was used depending on patient condition and side effects after transplantation. Continuous variables are presented as mean ± standard deviation and were analyzed using the two-tailed Student ttest or analysis of variance. Categorical variables, presented as proportions, were analyzed using Fisher exact test. Graft survival rates were calculated using the Kaplan-Meier method and compared among the groups using the log-rank test. Cox
regression analysis was used to evaluate risk factors for graft survival. P-values of
Effect of donor-specific antibodies and panel reactive antibodies in living donor liver transplant recipients Seung Hwan Song1, Myoung Soo Kim1,2, Jung Jun Lee3, Man Ki Ju1,2, Jae Geun Lee1,2, Juhan Lee1,2, Jin Sub Choi1,2, Gi Hong Choi1,2, Soon Il Kim1,2, Dong Jin Joo1,2 Department of Surgery and 2The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea
1 3
Purpose: Preformed circulating donor-specific antibodies (DSAs) immunologically challenge vascular endothelium and the bile duct. However, the liver is an immune-tolerant organ and can avoid immunological challenges. This study was undertaken to analyze the effects of DSAs after adult living donor liver transplantation (LDLT). Methods: We retrospectively reviewed 219 LDLT patients’ records treated at our center. Results: Of the 219 patients, 32 (14.6%) were DSA (+) and 187 (85.4%) were DSA (–). Class I DSAs were present in 18 patients, class II in seven patients, and both in seven patients. Seven patients (3.2%) showed DSA to HLA-A, four (1.8%) to HLA-B, seven (3.2%) to HLA-DR, and 14 (6.4%) to two or more HLAs. More DSAs were observed in female recipients than male recipients in the DSA (+) group. The DSA (+) group showed significantly higher levels of class I and II panel reactive antibody (PRA) than did the DSA (–) group. No significant intergroup differences were found between incidences of primary nonfunction, acute rejection, vascular complication, or biliary complication. There were no significant differences in graft survival rates between the two groups. However, the recipients with multiple DSAs tended to have more acute rejection episodes and events of biliary stricture and lower graft survival rates than did patients in the DSA (–) group. Conclusion: In LDLT, the presence of multiple DSAs and high PRA seemed to be associated with poor graft outcomes, although our results did not reach statistical significance. Large cohort studies are necessary to clarify the impact of DSA and PRA in LDLT. [Ann Surg Treat Res 2015;88(2):100-105] Key Words: Liver transplantation, Donor specific antibody, Acute rejection, Graft survival, Sensitization
INTRODUCTION Highly sensitized organ recipients are at greater risk of acute rejection, vascular complications, and poor graft survival [1-3]. Circulating donor-specific antibodies (DSAs) immunologically challenge the vascular endothelium and bile duct [4], but the liver is uniquely able to neutralize antibodies and escape from immunologic challenges [5,6]. However, the effects of DSAs on graft function and survival after liver transplantation remains controversial. Some authors suggest that a positive T lymphocyte cross match results in poor graft survival and more
Received June 19, 2014, Revised August 5, 2014, Accepted August 14, 2014 Corresponding Author: Dong Jin Joo Department of Surgery, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea Tel: +82-2-2228-2131, Fax: +82-2-313-8289 E-mail: [email protected]
100
acute rejection [7,8], whereas others conclude that a positive T lymphocyte cross match has no effect on graft outcome [9,10]. Additionally, the role of circulating preformed DSAs before liver transplantation is unclear. Consequently, the aim of this study was to determine if preformed circulating DSAs negatively affect graft outcome after living donor liver transplantation (LDLT).
METHODS The medical records of 219 adult LDLT patients that un
Copyright ⓒ 2015, the Korean Surgical Society cc Annals of Surgical Treatment and Research is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution NonCommercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Seung Hwan Song, et al: Effect of DSA and PRA in LDLT
derwent treatment at Yonsei University College of Medicine between June 2006 and August 2012 were retrospectively reviewed. Pediatric and second transplant cases were excluded. Patients were allocated to two groups according to the presence of DSA. DSAs were identified by panel reactive antibody (PRA) identification conducted by ELISA using the Lambda Cell Tray lymphocytotoxicity assay (One Lambda Inc., Canoga Park, CA, USA). Records were reviewed for clinical and immunological characteristics, acute rejection episodes, complications, and graft survival. The primary immunosuppressive therapy used posttrans plant was a tacrolimus-based agent. Induction therapy with interleukin-2 receptor antibody (basiliximab) was used, except in cases with identical HLA matching. Antimetabolite was used depending on patient condition and side effects after transplantation. Continuous variables are presented as mean ± standard deviation and were analyzed using the two-tailed Student ttest or analysis of variance. Categorical variables, presented as proportions, were analyzed using Fisher exact test. Graft survival rates were calculated using the Kaplan-Meier method and compared among the groups using the log-rank test. Cox
regression analysis was used to evaluate risk factors for graft survival. P-values of
