Influence of Preformed Antibodies in Liver Transplantation

Legáz, Isabel; Boix, Francisco; López, María Dolores; Alfaro, Rafael; Galián, José; Llorente, Santiago; Campillo, José A.; Botella, Carmen; Ramı́rez, Pablo; Sánchez‐Bueno, Francisco; Pons, J.A.; Moya‐Quiles, María Rosa; Minguela, Alfredo; Muro, Manuel

doi:10.3390/jcm9030708

Cited by 23 publications

(24 citation statements)

References 74 publications

(101 reference statements)

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“…As far as acute AMR, in contrast with a recent publication of Del Bello [23], we found no correlation between AMR and pretransplant HLA‐specific complement‐non‐binding DSA. However, Legaz et al also, like in our report, did not find a higher frequency of acute rejection in recipients with preformed DSA [24]. A probable explanation of these contradictory results might be differences in patient demographics and immunosuppressive regimens, and/or other unknown factors.…”

Section: Discussioncontrasting

confidence: 56%

De novo HLA Class II antibodies are associated with the development of chronic but not acute antibody‐mediated rejection after liver transplantation – a retrospective study

Kovandova¹,

Slavčev²,

Honsová

et al. 2020

Transpl. Int.

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Summary Donor‐specific antibodies (DSA) cause antibody‐mediated rejection (AMR); however, their pathogenic role has not yet been adequately investigated after liver transplantation. The aim of our study was to analyse the clinical significance of DSA and complement‐binding DSA for the prediction of AMR after liver transplantation. Our cohort included 120 liver recipients with assessed protocol biopsies one year post‐transplant. All patients had defined HLA‐specific and complement‐binding (C1q + and C3d+) antibodies before and in regular intervals after transplantation. The incidence of DSA was evaluated in relation with clinical and histopathological data in the liver allografts. A higher occurrence of acute AMR was observed in recipients with preformed complement‐binding DSA to HLA Class I antigens. Patients who developed chronic AMR had more frequently de novo‐produced antibodies against HLA Class II antigens (P = 0.0002). A correlation was also found between de novo‐formed C1q + and C3d+‐binding antibodies to HLA Class II antigens and the development of chronic AMR (P = 0.043). Our study implies that preformed complement‐binding DSA to HLA Class I antigens are related to increased risk of acute antibody‐mediated rejection, while chronic AMR is more frequent in patients with de novo‐produced antibodies to HLA Class II antigens after liver transplantation.

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Section: Discussioncontrasting

confidence: 56%

De novo HLA Class II antibodies are associated with the development of chronic but not acute antibody‐mediated rejection after liver transplantation – a retrospective study

Kovandova¹,

Slavčev²,

Honsová

et al. 2020

Transpl. Int.

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“… 5 Recent studies suggest that high levels of preformed DSA and de novo DSA can induce early graft rejection, accelerate liver fibrosis, and even accelerate early graft failure, leading to impaired graft and patient survival. 6 , 7 Therefore, physicians should be aware of the possible effects of preformed DSA on patient outcome after LT and establish an immunologic strategy for DSA to prevent potential detrimental effects.…”

Section: Introductionmentioning

confidence: 99%

Rituximab Desensitization in Liver Transplant Recipients With Preformed Donor-specific HLA Antibodies: A Japanese Nationwide Survey

Akamatsu

Hasegawa

Sakamoto

et al. 2021

Transplantation Direct

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Background. The significance of preformed donor-specific anti-HLA antibodies (DSAs) in liver transplant recipients is controversial. Moreover, there has been no established desensitization protocol for DSA-positive recipients. Methods. A Japanese nationwide survey was performed to investigate the clinical practice among preformed DSA-positive patients with special reference to rituximab desensitization. Results. There was a total of 47 cases, including 2 pediatric cases, in which rituximab (287 ± 159 mg [319 (50–916)/m 2 ]) was administered to desensitize preformed DSA. The decision for the indication of rituximab desensitization was based on a single-antigen assay in the majority of cases (83%, 39/47), and the most frequent protocol was rituximab monotherapy (n = 12) followed by quadruple treatment with rituximab tacrolimus, mycophenolate mofetil, and plasmapheresis (n = 11). The overall 1-, 3-, and 5-y graft and patient survival rates among adult patients were 85%, 83%, 83%, and 81%, 77%, 74%, respectively, while neither graft loss nor death was observed in the 2 pediatric cases. The 1-, 3-, and 12-mo cumulative incidence of antibody-mediated rejection (AMR) was 11%, 13%, and 13%, respectively. The incidence of AMR was significantly higher in the lower rituximab dose group than in the higher rituximab dose group (cutoff 300 mg/m 2 , 4% versus 24%, P = 0.041). The rate of infusion-related adverse drug reactions (ADRs) was 4.4%, and all ADRs were mild and self-limiting. A total of 99 ADRs among 27 patients were reported, none of which were severe adverse events associated with rituximab. Conclusions. The rituximab induction was well tolerated among DSA-positive liver transplant recipients with a satisfactory outcome. A rituximab dose >300 mg/m 2 was observed to achieve less incidence of the development of AMR.

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“…Although the liver was traditionally considered an immunologically privileged organ [61], nowadays liver transplantation in sensitized patients would have a detrimental effect on both patient and graft survival [62].…”

Section: Discussionmentioning

confidence: 99%

Identification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients

Boix

Legáz

Minhas

et al. 2020

Clinical and Experimental Immunology

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Summary Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+CD154+ and CD8+CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient–donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+CD154+ T cells (P = 0·001) and a low percentage of CD8+CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+CD154+ (P = 0·001) and CD8+CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+CD154+, CD8+CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+CD154+ and CD8+CD154+ T cells in parallel with other transplant factors.

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Influence of Preformed Antibodies in Liver Transplantation

Cited by 23 publications

References 74 publications

De novo HLA Class II antibodies are associated with the development of chronic but not acute antibody‐mediated rejection after liver transplantation – a retrospective study

De novo HLA Class II antibodies are associated with the development of chronic but not acute antibody‐mediated rejection after liver transplantation – a retrospective study

Rituximab Desensitization in Liver Transplant Recipients With Preformed Donor-specific HLA Antibodies: A Japanese Nationwide Survey

Identification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients

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