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

Kovandova, Barbora; Slavčev, Antonij; Honsová, Eva; Erhartová, Denisa; Skibová, J; Viklický, Ondřej; Trunečka, Pavel

doi:10.1111/tri.13763

Cited by 12 publications

(15 citation statements)

References 34 publications

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“…These persistent de novo antibodies increased the incidence of post-transplantation aGvHD and severely affected patient survival. Our study results showed that HLA-II antibodies were the main de novo HLA antibody, which is consistent with the results of some organ transplantation studies (18)(19)(20). This finding is also consistent with our previous study on post-kidney transplantation de novo HLA antibodies, showing that posttransplantation de novo DSA antibodies were mainly HLA-II antibodies (21).…”

Section: Discussionsupporting

confidence: 93%

“…The median platelet reconstitution time was 15 (10-36) days, 16 (10-98) days, 16 (10-70) days, and 14 (10-154) days in groups 1, 2, 3, and 4, respectively (P = 0.49). The median platelet reconstitution time was 12 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) and 15 (10-154) days in group 4a and group 4b, respectively. There were no statistical differences between the two groups and group 1 (P=0.32).…”

Section: Platelet Reconstitutionmentioning

confidence: 99%

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Posttransplant de novo DSA and NDSA affect GvHD, OS, and DFS after haplo-HSCT in patients without pre-existing HLA antibodies of hematological malignancies

et al. 2022

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To examine the production time, type, and MFI of post-transplantation de novo HLA antibodies, and their effects on haplo-HSCT outcomes, we retrospectively included 116 patients who were negative for pre-existing HLA antibodies. In total, 322 serum samples from pre-transplantation to post-transplantation were dynamically tested by Luminex and single-antigen bead reagents. Patients were divided into: HLA antibody persistently negative group (group 1), the de novo HLA antibody transiently positive group (group 2), the de novo HLA antibody non-persistently positive group (group 3), and the de novo HLA antibody persistently positive group (group 4). Group 4 included DSA+non-DSA (NDSA) (group 4a) and NDSA (group 4b) groups. The detection rate of de novo HLA antibodies was 75.9% (88/116). The median MFI for de novo HLA antibodies was 2439 (1033-20162). The incidence of II–IV aGvHD was higher in group 2 than in group 1 (52.6% vs 17.9%, P < 0.01); in group 4a than in group 1 (87.5% vs 17.9%, P < 0.001); and in group 4a than in group 4b (87.5% vs 40.0%, P = 0.001). The DFS (37.5% vs 85.7%, P < 0.01) and OS (37.5% vs 85.7%, P < 0.01) of group 4a were lower than those of group 1. The DFS (48.0% vs 85.7%, P < 0.01) and OS (56.0% vs 85.7%, P = 0.03) of group 4b were lower than those of group 1. Multivariate analysis showed that de novo HLA antibody being transiently positive (HR: 5.30; 95% CI: 1.71–16.42, P = 0.01) and persistently positive (HR: 5.67; 95% CI: 2.00–16.08, P < 0.01) were both associated with a higher incidence of II–IV aGvHD. Persistently positive de novo HLA antibodies were a risk factor for reduced DFS (HR: 6.57; 95% CI: 2.08–20.70, P < 0.01) and OS (HR: 5.51; 95% CI: 1.73–17.53, P < 0.01). DSA and NDSA can be detected since 15 days after haplo-HSCT in patients without pre-existing HLA antibodies, and affect aGvHD, DFS, and OS. Haplo-HSCT patients must be monitored for HLA antibodies changes for appropriate preventive clinical management, and we recommend that 1-month post-transplantation is the best test time point.

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Section: Discussionsupporting

confidence: 93%

Section: Platelet Reconstitutionmentioning

confidence: 99%

Posttransplant de novo DSA and NDSA affect GvHD, OS, and DFS after haplo-HSCT in patients without pre-existing HLA antibodies of hematological malignancies

et al. 2022

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“…Other series from Europe and Japan strongly associate the presence of de novo HLA antibodies to class II antigens (DSAs and non-DSAs) with CAMR, inflammation, and LAF[ 50 - 54 ]. Potential patho-mechanisms linking DSAs to LAF include destruction of microvasculature, non-microvascular antibody-dependent cell mediated cytotoxicity, activation of endothelial and stellate cells and portal myofibroblasts, and complement mediated chemotaxis[ 47 , 51 , 52 ].…”

Section: Chronic Antibody Mediated Rejectionmentioning

confidence: 99%

Long-term liver allograft fibrosis: A review with emphasis on idiopathic post-transplant hepatitis and chronic antibody mediated rejection

Vij¹,

Rammohan²,

Rela³

2022

WJH

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Liver transplantation (LT) is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease. With improvements in organ preservation techniques, perioperative care, and immunosuppression, there is better patient and graft survival following LT, and assessment of the liver allograft in long-term survivors is becoming increasingly important. Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults. However, no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients, as they have been transplanted for non-recurrent liver diseases. Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes. Pathological findings are frequently present in liver biopsies obtained after a year post LT. The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters. This narrative review summaries the factors predisposing to long-term liver allograft fibrosis, highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.

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“…DSAs are considered a risk factor for the development of AMCR, as they are a necessary, although insufficient, requirement for the diagnosis of AMCR[ 8 ]. Other risk factors for AMCR include possibly inadequate IS therapy [cyclosporine regimens or low concentrations of calcineurin inhibitors (CNIs)], recipient’s Mayo End-Stage Liver Disease (MELD) score > 15, young age at transplantation and re-transplantation.…”

Section: Incidence and Risk Factors For Chronic Rejectionmentioning

confidence: 99%

“…DSAs can either be existent before LT (preformed), and may disappear or persist, or they can be generated de novo after LT. Generally, preformed DSAs are more closely correlated to acute rejection, while de novo DSAs are more tied to AMCR[ 8 , 11 ]. De novo DSAs may appear in 0.4%-8% of patients 1 year after LT. O’Leary et al [ 4 ] showed that the prevalence of de novo DSAs was 62% in patients with CR and 38% in patients without CR ( P = 0.047).…”

Section: Role Of Donor Specific Antibodiesmentioning

confidence: 99%

Chronic rejection after liver transplantation: Opening the Pandora’s box

Angelico¹,

Sensi²,

Manzia³

et al. 2021

WJG

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Chronic rejection (CR) of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation. Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy, CR still represents an important cause of graft injury, which might be irreversible, leading to graft loss requiring re-transplantation. To date, we still do not fully appreciate the mechanisms underlying this process. In addition to T cell-mediated CR, which was initially the only recognized type of CR, recently a new form of liver allograft CR, antibody-mediated CR, has been identified. This has indeed opened an era of thriving research and renewed interest in the field. Liver biopsy is needed for a definitive diagnosis of CR, but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation. Moreover, the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury, which should not be disregarded. Therapies for CR may only be effective in the “early” phases, and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage. Herein, we provide an overview of the current knowledge and research on CR, focusing on early detection, identification of non-invasive biomarkers, immunosuppressive management, re-transplantation and future perspectives of CR.

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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

Cited by 12 publications

References 34 publications

Posttransplant de novo DSA and NDSA affect GvHD, OS, and DFS after haplo-HSCT in patients without pre-existing HLA antibodies of hematological malignancies

Posttransplant de novo DSA and NDSA affect GvHD, OS, and DFS after haplo-HSCT in patients without pre-existing HLA antibodies of hematological malignancies

Long-term liver allograft fibrosis: A review with emphasis on idiopathic post-transplant hepatitis and chronic antibody mediated rejection

Chronic rejection after liver transplantation: Opening the Pandora’s box

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