Donor-specific antibodies in liver transplantation

Vionnet, Julien; Sempoux, Christine; Pascual, Manuel; Sánchez‐Fueyo, Alberto; Colmenero, Jordi

doi:10.1016/j.gastre.2019.09.004

Cited by 4 publications

(11 citation statements)

References 90 publications

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“…Their ability to cause liver damage are predicated not only by their class (higher in class II than class I) and blood titer (higher for MFI ≥5000) but also by the immunoglobulin subclass and its ability to bind complement (mainly IgG3 DSA and C1q-binding DSA). 9,10 Most preformed DSA disappear after LT, especially if they belong to class I. 11 Regarding de novo DSA, the observed incidence depends on the MFI threshold and the study design, being low in the first 6 months after LT and increasing over time (up to 14% and 20% at 2.9 and 5.7 years after LT).…”

Section: Discussionmentioning

confidence: 99%

“…17 In LT, however, none of these strategies has shown any benefit over another and their clinical impact has yet to be confirmed. 9 Steroid pulses in our patient, for example, were initially administered without obtaining a clinical or histological response. It was only when the diagnosis of acute AMR was made and we added plasmapheresis and immunoglobulin therapy that the clinical state improved and ultimately resolved.…”

Section: Discussionmentioning

confidence: 99%

“…Preformed DSA are present in less than 20% of recipients. Their ability to cause liver damage are predicated not only by their class (higher in class II than class I) and blood titer (higher for MFI ≥5000) but also by the immunoglobulin subclass and its ability to bind complement (mainly IgG3 DSA and C1q‐binding DSA) 9,10 . Most preformed DSA disappear after LT, especially if they belong to class I 11 .…”

Section: Discussionmentioning

confidence: 99%

“…In the kidney transplant setting, anti‐humoral therapy is based on two complementary approaches: (1) the removal of harmful antibodies from the blood stream through plasmapheresis or immunoadsorption and (2) the modulation of various components of specific and/or innate immunity using strategies that include intravenous immunoglobulin, anti‐CD20 antibody (rituximab), antithymocyte globulin, proteasome inhibitors (bortezomib), anti‐C5 antibodies (eculizumab), or even splenectomy 17 . In LT, however, none of these strategies has shown any benefit over another and their clinical impact has yet to be confirmed 9 . Steroid pulses in our patient, for example, were initially administered without obtaining a clinical or histological response.…”

Section: Discussionmentioning

confidence: 99%

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Sinusoidal obstruction syndrome as a manifestation of acute antibody-mediated rejection after liver transplantation

Baliellas

Lladó

Serrano

et al. 2021

American Journal of Transplantation

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Liver allografts have greater resistance to antibody-mediated rejection (AMR) than allografts of other organs thanks to several mechanisms. These mechanisms include the presence of a unique sinusoidal microvascular hepatic circulation, the secretion of a soluble human leukocyte antigen (HLA) immune complex, platelet aggregate and complement component phagocytosis by Kupffer cells, the dual arterial and portal circulation of the liver, a homologous complement source, and the ability of the liver to regenerate. 1 However, emerging data suggest the importance of AMR due to donor-specific anti-HLA antibodies (DSA) following liver transplantation (LT). DSA have been associated with graft loss, chronic rejection, acute AMR, graft fibrosis, and/or death. 2 In particular, acute AMR is common when incompatible ABO livers are used, but it has also been reported in the setting of ABO compatibility. 3 Clinically, acute AMR is characterized

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Sinusoidal obstruction syndrome as a manifestation of acute antibody-mediated rejection after liver transplantation

Baliellas

Lladó

Serrano

et al. 2021

American Journal of Transplantation

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“…In recent years, there have been reports of donor-specific alloantibody (DSA)-associated liver graft rejection (1). The DSAs have been related to high risks of early acute rejection and death.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of pre-sensitization-related acute antibody-mediated rejection in a rat model of orthotopic liver transplantation

Yuanyi¹,

Zhang²,

Zhao³

et al. 2022

Ann Transl Med

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Background:To establish an animal model of pre-sensitization following liver transplantation either with or without immunosuppressors. To study whether accelerated liver rejection or acute antibody-mediated rejection (AMR) occurred and study the characteristics and potential mechanism in the animal model.Methods: Lewis (LEW) rats were subjected to liver [liver graft of Brown Norway (BN) rat] transplantation 2 weeks after lymphocyte injection (lymphocytes of BN rat; pre-sensitization). At 2 weeks after transplantation, serum samples of recipients were collected for antibody analysis to identify donor-specific alloantibody (DSA) level. The recipients were treated with or without a low dose of immunosuppressor (2 mg/kg). The liver grafts of each group were analyzed by hematoxylin and eosin (HE) stain, Masson stain, CK19, C4d, and CD20 immunohistochemical (IHC) stain, CD3, CD68, and CD86 immunofluorescence and transmission electron microscope (TEM) to study the characteristics of liver rejection. Moreover, cytotoxin-associated genes, M1 macrophages conversion-related proteins, and interleukin-6 (IL-6) signaling pathway proteins were detected by western blotting.Results: High level of DSA and accelerated liver rejection occurred in the pre-sensitized rat models following liver transplant. Accelerated liver graft rejection occurred in the pre-sensitized, post liver transplant rats regardless of whether a low dose immunosuppressor had been applied. Severe injury of the interlobular bile ducts and accelerated fibrosis could be observed. Moreover, evidence of endothelial injury, such as capillary inflammation, was found in the pre-sensitized, post-transplant rats. In addition, C4d deposition and M1 macrophages recruitment were also found in this sensitized followed transplant model, indicating that complement activation might occur in this model. The levels of IL-6, JAK1, STAT3, SHP2, and ERK1-2 were increased in the pre-sensitized, post-transplant rats.Conclusions: Pre-sensitized post liver transplant rats might be potential AMR models for further study.

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Lactic Acidosis, Hypoglycemia, and Eosinophilia: Novel Markers of Antibody‐Mediated Rejection Causing Graft Ischemia

et al. 2021

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Historically, minimal significance has been given to the humoral immune response after liver transplantation and despite antibodies against human leukocyte antigens (HLAs) being present in 10% to 20% of patients awaiting transplant, the incidence of antibody-mediated rejection (AMR) after ABO compatible (ABO-C) liver transplantation is low. (1) Donor-specific antibodies (DSAs) can lead to early graft loss, (2) but most patients awaiting liver transplantation are not screened for HLA sensitization, and serum DSA measurement is only undertaken if AMR is suspected. We describe 2 cases of AMR occurring within 1 week of ABO-C liver transplantation with previously unreported biochemical and histological characteristics.The first case was a 23-year-old woman who received a transplant for congenital hepatic fibrosis. She received a partial liver allograft (extended right lobe) from a deceased donor and developed recurrent fevers on day 2 after transplant without any infective source being evident. On postoperative day (POD) 5 she developed ascites and worsening abdominal pain, and blood tests revealed raised lactate, hypoglycemia, and eosinophilia (Fig. 1). There was additional evidence of graft dysfunction with elevations in alanine aminotransferase (ALT; 742 U/mL), bilirubin (335 μmol/L), and international normalized ratio (INR; 2.2), but no evidence of encephalopathy. An urgent liver biopsy demonstrated severe mixed T cell-mediated rejection (TCMR) and AMR with prominent eosinophils. In addition, foci of ischemic type necrosis and severe glycogen depletion of hepatocytes were present (Fig. 2). Complement component 4d (C4d) showed focal linear portal vein staining and HLA class 2 DSAs (DQ6, DQ7, and DR13), each with mean fluorescence intensities (MFIs) of >20,000 present in the patient's serum on POD 6. The patient did not respond to 2 courses of intravenous methylprednisolone (1 g); a repeat biopsy on POD 16 demonstrated strong C4d staining of the portal veins and microvasculature, and she was treated with plasma exchange. The patient was discharged on POD 31 and remains in good health 8 months after transplant.The second case was a 48-year-old woman who received a transplant for primary biliary cirrhosis with a whole-liver allograft from a deceased donor. On POD 6 this patient developed a similar

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Donor-specific antibodies in liver transplantation

Cited by 4 publications

References 90 publications

Sinusoidal obstruction syndrome as a manifestation of acute antibody-mediated rejection after liver transplantation

Sinusoidal obstruction syndrome as a manifestation of acute antibody-mediated rejection after liver transplantation

Characteristics of pre-sensitization-related acute antibody-mediated rejection in a rat model of orthotopic liver transplantation

Lactic Acidosis, Hypoglycemia, and Eosinophilia: Novel Markers of Antibody‐Mediated Rejection Causing Graft Ischemia

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