Afucosylation of HLA-specific IgG1 as a potential predictor of antibody pathogenicity in kidney transplantation

Bharadwaj, Pranay; Shrestha, Sweta; Pongrácz, Tamás; Catalano, Concetta; Sharma, Shilpee; Moine, Alaín Le; Haan, Noortje de; Murakami, Naoka; Riella, Leonardo V.; Holovska, Vanda; Wuhrer, Manfred; Marchant, Arnaud; Ackerman, Margaret E.

doi:10.1016/j.xcrm.2022.100818

Cited by 16 publications

(11 citation statements)

References 114 publications

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“…By contrast, anti-human platelet antigens antibodies are less fucosylated than total serum IgG1, leading to enhanced phagocytosis of IgG-binded platelets and increased disease severity ( 34 ). Accordingly, HLA-specific afucosylated IgG1 have been proposed to be a potential predictor of antibody pathogenicity ( 35 ), illustrating the importance of sugars in antibody functions.…”

Section: Intrinsic Features Of Anti-hla-i Antibodiesmentioning

confidence: 99%

Anti-HLA Class I alloantibodies in platelet transfusion refractoriness: From mechanisms and determinants to therapeutic prospects

Couvidou

Rojas-Jiménez²,

Dupuis³

et al. 2023

Front. Immunol.

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Patients with hematological disorders and severe thrombocytopenia require extensive and iterative platelet transfusion support. In these patients, platelet transfusion refractoriness represents a serious adverse transfusion event with major outcomes for patient care. Recipient alloantibodies against the donor HLA Class I antigens expressed at the cell surface of platelets result in a rapid removal of transfused platelets from the circulation and thus, therapeutic and prophylactic transfusion failure leading to a major bleeding risk. In this case, the only way to support the patient relies on the selection of HLA Class I compatible platelets, an approach restricted by the limited number of HLA-typed donors available and the difficulty of meeting the demand in an emergency. However, not all patients with anti-HLA Class I antibodies develop refractoriness to platelet transfusions, raising the question of the intrinsic characteristics of the antibodies and the immune-mediated mechanisms of platelet clearance associated with a refractory state. In this review, we examine the current challenges in platelet transfusion refractoriness and detail the key features of the antibodies involved that should be considered. Finally, we also provide an overview of future therapeutic strategies.

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Section: Intrinsic Features Of Anti-hla-i Antibodiesmentioning

confidence: 99%

Anti-HLA Class I alloantibodies in platelet transfusion refractoriness: From mechanisms and determinants to therapeutic prospects

Couvidou

Rojas-Jiménez²,

Dupuis³

et al. 2023

Front. Immunol.

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“…Darüber hinaus haben Patienten der Gruppe 3 nicht nur ein signifikant höheres Risiko für eine ABMR sondern auch für den Verlust der Transplantatniere [8]. Auch andere Publikationen bestätigen, dass es sich bei de novo DSA um einen Biomarker für eine mögliche ABMR sowie um einen Risikofaktor für ein Organversagen handelt [5,18,19], aber nicht jeder Patient mit einem DSA entwickelt eine ABMR [20,21].…”

Section: Hla-antikörper Und Abmrunclassified

Antikörpertestung in der Nierentransplantation

Dick,

Kugyelka,

Humpe

et al. 2023

Nephrologie aktuell

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ZUSAMMENFASSUNGDas HLA-System (HLA: humane Leukozytenantigene) spielt eine wichtige Rolle bei der Transplantation (Tx) der Niere. Daher ist der Nachweis von HLA-Antikörpern vor und nach der Tx entscheidend für die Betreuung des Patienten, wobei verschiedene Verfahren eingesetzt werden. Der Nachweis von donorspezifischen HLA-Antikörpern (DSA) ist gemäß Banff-Klassifikation 1 ein wichtiges Kriterium für die Diagnostik der antikörpervermittelten Abstoßung (ABMR: „antibody-mediated rejection“). Die Untersuchung auf präformierte sowie auf de novo DSA zu verschiedenen Zeitpunkten nach der Tx kann helfen, das individuelle Risiko für eine ABMR zu beurteilen.

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“…Higher DSA mean fluorescent intensity (MFI) measured by single-antigen bead assay, IgG3 subclass of immunodominant DSA and C1q-binding ability of DSA have been associated with a higher risk of AMR and allograft loss [56]. DSA Fc glycosylation may modulate antibody pathogenicity and AMR risk through differential activation of Fc receptors on natural killer (NK) and myeloid cells [60], though further studies are needed to validate these findings. Despite these characteristics, there are no methods to reliably predict who will develop AMR in kidney transplant recipients with dnDSA and stable kidney function.…”

Section: How Should De-novo Donor-specific Antibodies Be Managed In K...mentioning

confidence: 99%

Antibody-mediated rejection: prevention, monitoring and treatment dilemmas

Rodríguez-Ramírez

Jurdi

Konvalinka

et al. 2022

Current Opinion in Organ Transplantation

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Purpose of reviewAntibody-mediated rejection (AMR) has emerged as the leading cause of late graft loss in kidney transplant recipients. Donor-specific antibodies are an independent risk factor for AMR and graft loss. However, not all donor-specific antibodies are pathogenic. AMR treatment is heterogeneous due to the lack of robust trials to support clinical decisions. This review provides an overview and comments on practical but relevant dilemmas physicians experience in managing kidney transplant recipients with AMR. Recent findingsActive AMR with donor-specific antibodies may be treated with plasmapheresis, intravenous immunoglobulin and corticosteroids with additional therapies considered on a case-by-case basis. On the contrary, no treatment has been shown to be effective against chronic active AMR. Various biomarkers and prediction models to assess the individual risk of graft failure and response to rejection treatment show promise.

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Afucosylation of HLA-specific IgG1 as a potential predictor of antibody pathogenicity in kidney transplantation

Cited by 16 publications

References 114 publications

Anti-HLA Class I alloantibodies in platelet transfusion refractoriness: From mechanisms and determinants to therapeutic prospects

Anti-HLA Class I alloantibodies in platelet transfusion refractoriness: From mechanisms and determinants to therapeutic prospects

Antikörpertestung in der Nierentransplantation

Antibody-mediated rejection: prevention, monitoring and treatment dilemmas

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