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(1) Background: We aimed to investigate the outcomes of human leukocyte antigen (HLA)-incompatible transplantation for patients who received desensitization with intravenous immunoglobulins (IVIg), plasmapheresis, and rituximab. (2) Methods: A comprehensive search of multiple electronic databases to identify studies that utilized desensitization was conducted. The random-effects model was used to calculate the pooled rates and the 95% confidence interval (CI). (3) Results: A total of 1517 studies were initially identified. From these, 16 studies met the inclusion criteria, encompassing 459 patients, with a mean age of 45 years, of whom 40.8% were male. CDC crossmatch was positive in 68.3% (95% CI: 43.5–85.8; I2 87%), and 89.4% (95% CI: 53.4–98.4%; I2 89.8%) underwent living-donor transplantation. The 1-year graft survival pooled rate was 88.9% (95% CI: 84.8–92; I2 0%) and the 5-year graft survival rate was 86.1% (95% CI: 81.2–89.9; I2 0%). The 1-year patient survival rate was 94.2% (95% CI: 91–96.3; I2 0%), and the 5-year patient survival rate was 88.9% (95% CI: 83.5–92.7%; I2 7.7%). The rate of antibody-mediated rejection was 37.7% (95% CI: 25–52.3; I2 80.3%), and the rate of acute cell-mediated rejection was 15.1% (95% CI: 9.1–24; I2 55%). (4) Conclusions: Graft and patient survival are favorable in highly sensitized patients who undergo desensitization using IVIg, plasmapheresis, and rituximab for HLA-incompatible transplantation. [ABSTRACT FROM AUTHOR]

(1) Background: We aimed to investigate the outcomes of human leukocyte antigen (HLA)-incompatible transplantation for patients who received desensitization with intravenous immunoglobulins (IVIg), plasmapheresis, and rituximab. (2) Methods: A comprehensive search of multiple electronic databases to identify studies that utilized desensitization was conducted. The random-effects model was used to calculate the pooled rates and the 95% confidence interval (CI). (3) Results: A total of 1517 studies were initially identified. From these, 16 studies met the inclusion criteria, encompassing 459 patients, with a mean age of 45 years, of whom 40.8% were male. CDC crossmatch was positive in 68.3% (95% CI: 43.5–85.8; I2 87%), and 89.4% (95% CI: 53.4–98.4%; I2 89.8%) underwent living-donor transplantation. The 1-year graft survival pooled rate was 88.9% (95% CI: 84.8–92; I2 0%) and the 5-year graft survival rate was 86.1% (95% CI: 81.2–89.9; I2 0%). The 1-year patient survival rate was 94.2% (95% CI: 91–96.3; I2 0%), and the 5-year patient survival rate was 88.9% (95% CI: 83.5–92.7%; I2 7.7%). The rate of antibody-mediated rejection was 37.7% (95% CI: 25–52.3; I2 80.3%), and the rate of acute cell-mediated rejection was 15.1% (95% CI: 9.1–24; I2 55%). (4) Conclusions: Graft and patient survival are favorable in highly sensitized patients who undergo desensitization using IVIg, plasmapheresis, and rituximab for HLA-incompatible transplantation.

Introduction: While donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been implicated in graft rejection in solid organ transplantation, their role in hematopoietic stem-cell transplantation (HSCT) remains unclear. Aim: The aim of this study is to study the role of DSA for proper donor selection and its effect in the setting of allogeneic HSCT. Methodology: HLA A, B, C, DRB1, and DQB1 high-resolution typing, and DSA cross match (XM) of patients (n = 73) and their prospective donors (n = 74) were assessed. A case–control study was designed retrospectively to evaluate the effect of pre- existing DSAs on engraftment. Thirty-five cases with 5/10 HLA alleles mismatches and 38 cases with full HLA matched, these two controls were selected for comparison. These were matched for disease, graft type, conditioning regimen, age, gender, blood group, and sensitizing events. DSAs were tested with solid-phase assay (Luminex 100/200 platform). Results: DSAs were detected in six of 35 patients (17%); however, donors selected for transplantation were all negative for DSA crossmatch. These six patients who underwent haploidentical (HI) transplants had antibodies against Class I and II. One patient carried antibodies against both classes. A patient who experienced primary graft failure had a second HI transplant. No other known factors that could negatively influence engraftment were associated with the development of graft failure in this patient. Conclusions: DSAs are not associated with graft rejection in patients undergoing HI stem-cell transplantation. Anti-HLA sensitization should be evaluated routinely in HSCT with HLA mismatched donors for a better outcome.

Background : The presence of preformed donor-specific antibodies in recipient serum against anti-human leukocyte antigen is a significant risk factor that negatively affects the outcomes of intestinal transplantation. Avoiding high-risk intestinal transplantation by physical and virtual cross matches has had limited success due to time constraints and ineffective correlation, respectively. Methods : We developed a guideline to improve the association between physical and virtual cross matches using the retrospective data of 56 consecutive primary adult isolated intestinal transplantations from a single center. Results : The mean fluorescence intensity of 2,000 for positive donor-specific antibodies revealed the best association between physical and virtual cross matches among different cut-off values, but with an unacceptable false positive rate of 54%. An enhanced virtual cross match with the summation of the mean fluorescence intensity of each anti- human leukocyte antigen improved the association between physical and virtual cross matches, with a sensitivity of 83% and specificity of 98%. Conclusions: This enhanced virtual cross match more effectively predicts high-risk intestinal transplantation and is a better substitute for physical cross-match than the current virtual cross match. It also helps to avoid ill-considered abandonment of intestinal transplantation that is unnecessarily deemed high risk based on a simple virtual cross match.

Introduction: While donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been implicated in graft rejection in solid organ transplantation, their role in hematopoietic stem-cell transplantation (HSCT) remains unclear. Aim: The aim of this study is to study the role of DSA for proper donor selection and its effect in the setting of allogeneic HSCT. Methodology: HLA A, B, C, DRB1, and DQB1 high-resolution typing, and DSA cross match (XM) of patients (n = 73) and their prospective donors (n = 74) were assessed. A case--control study was designed retrospectively to evaluate the effect of pre- existing DSAs on engraftment. Thirty-five cases with 5/10 HLA alleles mismatches and 38 cases with full HLA matched, these two controls were selected for comparison. These were matched for disease, graft type, conditioning regimen, age, gender, blood group, and sensitizing events. DSAs were tested with solid-phase assay (Luminex 100/200 platform). Results: DSAs were detected in six of 35 patients (17%); however, donors selected for transplantation were all negative for DSA crossmatch. These six patients who underwent haploidentical (HI) transplants had antibodies against Class I and II. One patient carried antibodies against both classes. A patient who experienced primary graft failure had a second HI transplant. No other known factors that could negatively influence engraftment were associated with the development of graft failure in this patient. Conclusions: DSAs are not associated with graft rejection in patients undergoing HI stem-cell transplantation. Anti-HLA sensitization should be evaluated routinely in HSCT with HLA mismatched donors for a better outcome. [ABSTRACT FROM AUTHOR]

IntroductionOur goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR).MethodsSerum anti-Human Leukocyte Antigen (HLA) antibodies were determined using class I and class II antibody-coated latex beads (FlowPRATM Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch.ResultsWe studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%; P = 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed de novo anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA.ConclusionOur results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR.

Introduction: Our goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR). Methods: Serum anti-Human Leukocyte Antigen (HLA) antibodies were determined using class I and class II antibody-coated latex beads (FlowPRATM Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch. Results: We studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%; P = 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed de novo anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA. Conclusion: Our results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR. [ABSTRACT FROM AUTHOR]

Background: The presence of preformed donor-specific antibodies in recipient serum against anti-human leukocyte antigen is a significant risk factor that negatively affects the outcomes of intestinal transplantation. Avoiding high-risk intestinal transplantation by physical and virtual cross matches has had limited success due to time constraints and ineffective correlation, respectively., Methods: We developed a guideline to improve the association between physical and virtual cross matches using the retrospective data of 56 consecutive primary adult isolated intestinal transplantations from a single center., Results: The mean fluorescence intensity of 2,000 for positive donor-specific antibodies revealed the best association between physical and virtual cross matches among different cut-off values, but with an unacceptable false positive rate of 54%. An enhanced virtual cross match with the summation of the mean fluorescence intensity of each anti-human leukocyte antigen improved the association between physical and virtual cross matches, with a sensitivity of 83% and specificity of 98%., Conclusions: This enhanced virtual cross match more effectively predicts high-risk intestinal transplantation and is a better substitute for physical cross-match than the current virtual cross match. It also helps to avoid ill-considered abandonment of intestinal transplantation that is unnecessarily deemed high risk based on a simple virtual cross match., (Copyright © 2021 The Korean Society for Transplantation.)

In antibody-mediated rejection (ABMR), the graft endothelium is at the forefront of the kidney transplant against the assault from the recipient's humoral immune system, and is a target of the latter. The present study investigated the effect of antibodies against human leukocyte antigen (HLA) class I (anti-HLAI) on the immunological properties of human glomerular endothelial cells. Additionally, the effect of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) inhibitor (everolimus), or the general control nonderepressible 2 kinase (GCN2K) activator (halofuginone) on anti-HLAI antibody-mediated alterations was assessed. Cell integrity was examined, an lactate dehydrogenase (LDH) release assay was performed and cleaved caspase-3 levels were determined. Furthermore, cell proliferation was analyzed by performing a bromodeoxyuridine assay and the cellular proteins involved in signal transduction or immune effector mechanisms were assessed via western blotting. IL-8, monocyte chemoattractive protein-1 (MCP-1), von Willebrand factor (vWF) and transforming growth factor-beta 1 (TGF-β1) were assayed via ELISA. The results revealed that anti-HLAI triggered integrin signaling, activated mTOR and GCN2K, preserved cell integrity and promoted cell proliferation. Additionally, by increasing intercellular adhesion molecule 1 (ICAM-1), HLA-DR, IL-8 and MCP-1 levels, anti-HLAI enhanced the ability of immune cells to interact with endothelial cells thus facilitating graft rejection. Contrarily, by upregulating CD46 and CD59, anti-HLAI rendered the endothelium less vulnerable to complement-mediated injury. Finally, by enhancing vWF and TGF-β1, anti-HLAI may render the endothelium prothrombotic and facilitate fibrosis and graft failure, respectively. According to our results, mTORC1 inhibition and GCN2K activation may prove useful pharmaceutical targets, as they prevent cell proliferation and downregulate ICAM-1, IL-8, MCP-1 and TGF-β1. mTORC1 inhibition also decreases vWF. [ABSTRACT FROM AUTHOR]