Antibody‐mediated rejection after liver transplantation—relevance of C1q and C3d‐binding antibodies

Kovandova, Barbora; Slavčev, Antonij; Sekerkova, Zuzana; Honsová, Eva; Trunečka, Pavel

doi:10.1111/tan.13354

Cited by 11 publications

(8 citation statements)

References 12 publications

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“…On the other hand, in our cohort, preformed complement‐binding DSA directed to HLA Class I antigens, as defined by the C1q and C3d techniques, came up as a clear predictor for the development of acute AMR. This finding is in concordance with our preliminary results [21] and also with the report of Kozlowski et al, showing higher risk of AMR in recipients with pretransplant C1q‐binding DSA [25]. This indicates that liver recipients with preformed complement‐binding HLA Class I DSA may be considered as a high‐risk group and should be carefully monitored after transplantation.…”

Section: Discussionsupporting

confidence: 93%

“…In line with these results, a number of published reports showed increased incidence of rejection, graft dysfunction and worse graft survival in liver recipients with DSA [10–17]; however, the relevance of complement‐binding DSA for the risk for the development of liver AMR is still unclear [18–20]. In a pilot study of our centre, all liver recipients with pre‐transplant complement‐binding DSA developed severe AMR after transplantation; nevertheless, further investigation would be needed to clarify the role of persistent and de novo ‐produced antibodies [21]. The goal of our study was therefore to evaluate the clinical significance of preformed, persistent and de novo ‐produced complement‐binding DSA (as defined by solid‐phase single‐antigen (SA) bead techniques) for prediction of antibody‐mediated rejection after liver transplantation.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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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“…After removing the 5 largest cohort studies (in terms of the number of patients included) from the analysis ( 37 , 39 , 42 , 45 , 48 ), the presence of dn-DSA remained significantly associated with an increased risk of an outcome (OR 4.44; 95% CI 1.93–10.21; P < 0.001), and the heterogeneity across the studies decreased from 58.19 to 52.33% ( Figure S14 ).…”

Section: Resultsmentioning

confidence: 99%

“…The 225 full-text articles were found for possible eligibility with regard to the inclusion criteria. Finally, 15 studies and 2016 patients were included in the final systematic review and meta-analysis, including 5 studies with data on the allograft loss (36)(37)(38)(39)(40), and 10 studies with data on rejection (41)(42)(43)(44)(45)(46)(47)(48)(49)(50). A flow diagram of the article selection process is demonstrated in Figure 1.…”

Section: Study Identification and Characteristicsmentioning

confidence: 99%

De Novo Donor Specific Antibody and Long-Term Outcome After Liver Transplantation: A Systematic Review and Meta-Analysis

et al. 2020

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BackgroundThe impact of de novo anti-HLA donor-specific alloantibodies (DSA) which develop after long-term liver transplantation (LT) remains controversial and unclear. The aim of this study was to investigate the role of de novo DSAs on the outcome in LT.MethodsWe did a systematic review and meta-analysis of observational studies published until Dec 31, 2019, that reported de novo DSA outcome data (≥1 year of follow-up) after liver transplant. A literature search in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus and Web of Science Core Collection databases was performed.ResultsOf 5,325 studies identified, 15 fulfilled our inclusion criteria. The studies which reported 2016 liver transplant recipients with de novo DSAs showed an increased complication risk, i.e. graft loss and chronic rejection (OR 3.61; 95% CI 1.94–6.71, P < 0.001; I2 58.19%), and allograft rejection alone (OR 6.43; 95% CI: 3.17–13.04; P < 0.001; I2 49.77%); they were compared to patients without de novo DSAs. The association between de novo DSAs and overall outcome failure was consistent across all subgroups and sensitivity analysis.ConclusionsOur study suggested that de novo DSAs had a significant deleterious impact on the liver transplant risk of rejection. The routine detection of de novo DSAs may be beneficial as noninvasive biomarker-guided risk stratification.

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“…However, the clinical relevance of all the detected DSAs remains unclear because the presence of DSAs does not always correlate with complement-mediated cytotoxicity crossmatching and may not induce AMR. Recently, C1q-and C3d-binding assays were introduced as methods for predicting the presence of complement-binding functional antibodies; however, the prognostic value of these tests remains controversial [2][3][4][5][6][7][8]. In particular, the clinical significance of preformed DSAs (pDSAs) with complement-binding activities has been not fully evaluated.…”

Section: Introductionmentioning

confidence: 99%

C3d-Positive Preformed DSAs Tend to Persist and Result in a Higher Risk of AMR after Kidney Transplants

Choi

Lee

Park

et al. 2020

JCM

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C3d-binding assays have been introduced as methods for the prediction of the presence of complement-binding functional antibodies; however, the prognostic value of C3d-positive preformed donor-specific antibodies (pDSAs) has not been fully evaluated. In this study, we performed a retrospective investigation of the association of pDSAs and their C3d-binding capacity with one-year clinical outcomes. pDSAs were defined as donor-specific antibodies (DSAs) that were produced before kidney transplants (KTs) (pre-pDSAs) or within the first four weeks after KTs, owing to rebound immune response (post-pDSAs). Of 455 adult KT recipients, pre-pDSAs and post-pDSAs were found in 56 (12.3%) and 56 (12.3%) recipients, respectively, and C3d-positive post-pDSAs were found in 13 recipients (2.9%) in total. Approximately half of the C3d-negative pre-pDSAs (37/73, 50.7%) disappeared after transplantation; however, all C3d-positive pre-pDSAs (8/8, 100%) persisted after transplantation despite desensitization (p = 0.008). C3d-positive pDSAs were significantly associated with a higher incidence and risk of AMR (p < 0.001, OR 94.467–188.934). Identification of the C3d-binding activity of pDSAs before and early after KT is important for predicting the persistence of pDSAs and the risk of AMR induced by the presence of pDSAs.

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Antibody‐mediated rejection after liver transplantation—relevance of C1q and C3d‐binding antibodies

Cited by 11 publications

References 12 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

De Novo Donor Specific Antibody and Long-Term Outcome After Liver Transplantation: A Systematic Review and Meta-Analysis

C3d-Positive Preformed DSAs Tend to Persist and Result in a Higher Risk of AMR after Kidney Transplants

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