SAT-440-Molecular fingerprint of T cell-mediated and antibody-mediated rejection after human liver transplantation

2019 ◽  
Vol 70 (1) ◽  
pp. e830
Author(s):  
Anne Höfer ◽  
Danny Jonigk ◽  
Björn Hartleben ◽  
Robert Geffers ◽  
Murielle Verboom ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
T Cell ◽  
Human Liver ◽  
Molecular Fingerprint ◽  
Antibody Mediated Rejection

scholarly journals Deletion of donor-reactive T cell clones following human liver transplantation

immuneACCESS ◽  
2019 ◽  
Author(s):  
TM Savage ◽  
BA Shonts ◽  
S Lau ◽  
A Obradovic ◽  
H Robins ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
T Cell ◽  
Human Liver ◽  
T Cell Clones ◽  
Cell Clones

Acute and Chronic Rejection in Liver Transplantation

2019 ◽  
Author(s):  
Ester Coelho Little ◽  
Marina Berenguer
Keyword(s):  
Liver Transplantation ◽  
T Cell ◽  
Autoimmune Hepatitis ◽  
Chronic Rejection ◽  
Protective Factor ◽  
De Novo ◽  
Point Of View ◽  
Potential Implication ◽  
Antibody Mediated Rejection ◽  
Cellular Rejection

Advances in immunosuppression have improved the outcome of transplantation. Although early cellular rejection does not adversely impact transplantation outcome, late cellular rejection appears to behave differently from both a clinical and a histologic point of view, potentially resulting in poor outcomes. Histologic assessments continue to play an important role in the diagnosis and management of liver allograft rejection. Former conditions known as “de novo autoimmune hepatitis” and “idiopathic posttransplantation chronic hepatitis” are currently labeled “atypical cases of rejection” and late T cell–mediated rejection. There is increasing evidence to suggest that central perivenulitis may be an important manifestation of these immune conditions. In addition, although the liver appears relatively resistant to donor-specific antibody–mediated injury, alloantibody-mediated adverse consequences are increasingly being recognized, including cases of acute and chronic antibody-mediated rejection and the potential implication of atypical immune-mediated manifestations of rejection, particularly late and chronic rejection. Judicious immunosuppression appears to be a common protective factor against these complications. This review contains 5 figures, 5 tables, and 72 references. Key words: antibody-mediated rejection, chronic rejection, de novo autoimmune hepatitis, fibrosis, idiopathic posttransplantation hepatitis, late rejection, liver transplantation, plasma cell–rich rejection, T cell–mediated rejection

Acute and Chronic Rejection in Liver Transplantation

2019 ◽  
Author(s):  
Ester Coelho Little ◽  
Marina Berenguer
Keyword(s):  
Liver Transplantation ◽  
T Cell ◽  
Autoimmune Hepatitis ◽  
Chronic Rejection ◽  
Protective Factor ◽  
De Novo ◽  
Point Of View ◽  
Potential Implication ◽  
Antibody Mediated Rejection ◽  
Cellular Rejection

Advances in immunosuppression have improved the outcome of transplantation. Although early cellular rejection does not adversely impact transplantation outcome, late cellular rejection appears to behave differently from both a clinical and a histologic point of view, potentially resulting in poor outcomes. Histologic assessments continue to play an important role in the diagnosis and management of liver allograft rejection. Former conditions known as “de novo autoimmune hepatitis” and “idiopathic posttransplantation chronic hepatitis” are currently labeled “atypical cases of rejection” and late T cell–mediated rejection. There is increasing evidence to suggest that central perivenulitis may be an important manifestation of these immune conditions. In addition, although the liver appears relatively resistant to donor-specific antibody–mediated injury, alloantibody-mediated adverse consequences are increasingly being recognized, including cases of acute and chronic antibody-mediated rejection and the potential implication of atypical immune-mediated manifestations of rejection, particularly late and chronic rejection. Judicious immunosuppression appears to be a common protective factor against these complications. This review contains 5 figures, 5 tables, and 72 references. Key words: antibody-mediated rejection, chronic rejection, de novo autoimmune hepatitis, fibrosis, idiopathic posttransplantation hepatitis, late rejection, liver transplantation, plasma cell–rich rejection, T cell–mediated rejection

PS-207-Molecular classifier for T-cell-mediated and antibody-mediated rejection after liver transplantation

2019 ◽  
Vol 70 (1) ◽  
pp. e137-e138
Author(s):  
Anne Höfer ◽  
Danny Jonigk ◽  
Björn Hartleben ◽  
Robert Geffers ◽  
Frank Klawonn ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
T Cell ◽  
Antibody Mediated Rejection ◽  
Molecular Classifier

Elevation of CD4+ Differentiated Memory T Cells Is Associated With Acute Cellular and Antibody-Mediated Rejection After Liver Transplantation

2013 ◽  
Vol 95 (12) ◽  
pp. 1512-1520 ◽  
Author(s):  
Undine A. Gerlach ◽  
Katrin Vogt ◽  
Stephan Schlickeiser ◽  
Christian Meisel ◽  
Mathias Streitz ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
T Cells ◽  
Memory T Cells ◽  
Antibody Mediated Rejection

scholarly journals Is ABO-Incompatible Living Donor Liver Transplantation Really a Good Alternative for Pediatric Recipients?

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 600
Author(s):  
Catherine de Magnée ◽  
Louise Brunée ◽  
Roberto Tambucci ◽  
Aurore Pire ◽  
Isabelle Scheers ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Living Donor ◽  
Living Donor Liver Transplantation ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Humoral Rejection ◽  
Donor Liver ◽  
Retrospective Case ◽  
Donor Liver Transplantation ◽  
Antibody Mediated Rejection

Background: ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been proposed to compensate for donor shortage. To date, few studies have reported detailed ABOi LDLT results in large series of pediatric patients. C4d complement deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in solid organ transplantation. Methods: A retrospective case–control study was conducted, comparing clinical outcomes of each of 34 consecutive pediatric ABOi LDLT recipients with those of 2 non-ABOi pairs (n = 68), matched according to pre-transplant diagnostic criteria, age, and date of transplantation. In addition, we studied the C4d immunostaining pattern in 22 ABOi and in 36 non-ABOi recipients whose liver biopsy was performed within the first 4 post-transplant weeks for suspected acute rejection. Results: The incidence of biliary complications was higher in ABOi recipients (p < 0.05), as were the incidence of acute humoral rejection (p < 0.01) and the incidence of retransplantation (p < 0.05). All children who required retransplantation were older than 1 year at the time of ABOi LDLT. Positive C4d immunostaining was observed in 13/22 (59%) ABOi recipients versus 3/36 (8.3%) non-ABOi recipients (p < 0.0001). Conclusions: ABOi LDLT is a feasible option for pediatric end-stage liver disease but carries increased risks for the recipient, especially for children older than 1 year, even with a specific preparation protocol. C4d immunostaining may be a hallmark of acute humoral rejection in ABOi liver transplantation.

scholarly journals Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nathalie M. Schmidt ◽  
Peter A. C. Wing ◽  
Mariana O. Diniz ◽  
Laura J. Pallett ◽  
Leo Swadling ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Liver ◽  
Lipid Droplets ◽  
Ex Vivo ◽  
Functional Cure ◽  
Carcinogenic Activity ◽  
Attractive Therapeutic Target ◽  
Tcr Signalling

AbstractDetermining divergent metabolic requirements of T cells, and the viruses and tumours they fail to combat, could provide new therapeutic checkpoints. Inhibition of acyl-CoA:cholesterol acyltransferase (ACAT) has direct anti-carcinogenic activity. Here, we show that ACAT inhibition has antiviral activity against hepatitis B (HBV), as well as boosting protective anti-HBV and anti-hepatocellular carcinoma (HCC) T cells. ACAT inhibition reduces CD8+ T cell neutral lipid droplets and promotes lipid microdomains, enhancing TCR signalling and TCR-independent bioenergetics. Dysfunctional HBV- and HCC-specific T cells are rescued by ACAT inhibitors directly ex vivo from human liver and tumour tissue respectively, including tissue-resident responses. ACAT inhibition enhances in vitro responsiveness of HBV-specific CD8+ T cells to PD-1 blockade and increases the functional avidity of TCR-gene-modified T cells. Finally, ACAT regulates HBV particle genesis in vitro, with inhibitors reducing both virions and subviral particles. Thus, ACAT inhibition provides a paradigm of a metabolic checkpoint able to constrain tumours and viruses but rescue exhausted T cells, rendering it an attractive therapeutic target for the functional cure of HBV and HBV-related HCC.

scholarly journals A novel MSC-based immune induction strategy for ABO-incompatible liver transplantation: a phase I/II randomized, open-label, controlled trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingcai Zhang ◽  
Jiebin Zhang ◽  
Huimin Yi ◽  
Jun Zheng ◽  
Jianye Cai ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Hepatic Failure ◽  
Therapeutic Option ◽  
Controlled Trial ◽  
Trial Registration ◽  
Biliary Complications ◽  
Open Label ◽  
Antibody Mediated Rejection ◽  
Link Type ◽  
Induction Strategy

Abstract Background ABO-incompatible liver transplantation (ABO-i LT) has become a rescue therapeutic option for patients with severe hepatic failure. Although the use of rituximab greatly reduces the morbidity of antibody-mediated rejection (AMR), severe adverse effects, such as infection and biliary complications, still seriously threaten the survival of transplant recipients. The aim of this study was to evaluate the safety and feasibility of using mesenchymal stem cells (MSCs) to replace rituximab in ABO-i LT. Methods Twenty-two patients with severe hepatic failure undergoing ABO-i LT were enrolled and randomly divided into two groups: the MSC group and the rituximab group. The safety of the application of MSCs and the incidence of allograft rejection, including antibody-mediated rejection (AMR) and acute cellular rejection (ACR), were evaluated in both groups at the 2-year follow-up period as primary endpoints. Recipients and graft survival and other postoperative complications were compared as secondary endpoints. Results No severe MSC-related adverse events were observed during the trial. MSC treatment yielded comparable, if not better, results than rituximab at decreasing the incidence of acute rejection (9.1% vs 27.3%). Inspiringly, compared to those in the rituximab group, the rates of biliary complications (0% vs 45.5%) and infection (9.1% vs 81.8%) were significantly decreased in the MSC group. In addition, there were no significant differences in 2-year graft and recipient survival between the two groups (81.8% vs 72.7%). Conclusions Our data show that MSC transfusion is comparable to rituximab treatment for AMR prophylaxis following ABO-i LT. Additionally, the results indicate that MSCs are more beneficial to the prevention of infection and biliary complications and may be introduced as a novel immunosuppressive approach for ABO-i LT. Trial registration Trial registration: chictr.org.cn, ChiCTR2000037732. Registered 31 August 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=57074.

scholarly journals Preceding T-Cell-Mediated Rejection Is Associated with the Development of Chronic Active Antibody-Mediated Rejection by de Novo Donor-Specific Antibody

Nephron ◽  
2020 ◽  
pp. 1-5
Author(s):  
Takahiro Tsuji ◽  
Sari Iwasaki ◽  
Keishi Makita ◽  
Teppei Imamoto ◽  
Naomichi Ishidate ◽  
...  
Keyword(s):  
T Cell ◽  
Specific Antibody ◽  
De Novo ◽  
Control Group ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaries ◽  
The Mean ◽  
Microvascular Inflammation ◽  
Renal Allograft Loss ◽  
Allograft Loss

<b><i>Aim:</i></b> Chronic active antibody-mediated rejection (CAABMR) is an important cause of late-stage renal allograft loss. Early inflammatory events such as acute rejection and infection after transplantation are considered to be the risk factors of de novo donor-specific antibody (dnDSA) production. In this study, we investigated the relationship between pre­disposing T-cell-mediated rejection and dnDSA-positive CAABMR. <b><i>Methods:</i></b> We recruited 365 patients who underwent ABO-compatible renal transplantation at our hospital. Among them, 16 patients diagnosed as having dnDSA-positive CAABMR were designated as a CAABMR group, and 38 randomly selected patients were designated as a control group. All biopsies from 1 month after transplantation were included in the study. The presence or absence of borderline changes (BLCs), acute T-cell-mediated rejection (ATMR), microvascular inflammation (MVI), and C4d positive on peritubular capillaries (C4d-P) was examined. <b><i>Results:</i></b> In the CAABMR group, BLC/ATMR was found in 12 cases (75%), and the mean duration until appearance of BLC/ATMR was 282.7 ± 328.7 days. C4d-P was found in 11 cases (68.8%), and the mean duration until its appearance was 1,432 ± 1,307 days. MVI was found in all cases, and the mean duration until its appearance was 1,333 ± 1,126 days. The mean duration until diagnosis of CAABMR was 2,268 ± 1,191 days. In the control group, BLC/ATMR was found in 13 cases (34.2%), and the mean duration until the appearance of BLC/ATMR was 173.1 ± 170.4 days. C4d-P was found in 2 cases (5.3%), and the durations until its appearance were 748 and 1,881 days. No cases of MVI were found in the control group. The frequency of BLC/ATMR was significantly higher in the CAABMR group (<i>p</i> &#x3c; 0.01). <b><i>Conclusion:</i></b> Preceding BLC/ATMR is associated with the development of CAABMR with dnDSA.

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