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Recent advances in renal transplantation: antibody-mediated rejection takes center stage.

Pouliquen E, Koenig A, Chen CC, Sicard A, Rabeyrin M, Morelon E, Dubois V, Thaunat O - F1000Prime Rep (2015)

Bottom Line: Unfortunately, this progress has not yet translated into better outcomes for patients.Indeed, in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction.This review provides an overview of the current knowledge of antibody-mediated rejection and discusses future interesting research directions.

View Article: PubMed Central - PubMed

Affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Transplantation, Néphrologie et Immunologie Clinique Lyon France ; Institut National de la Santé et de la Recherche Médicale U1111, Lyon France ; Unité de Formation et de Recherche Lyon Est, Université de Lyon Lyon France.

ABSTRACT
Overlooked for decades, antibodies have taken center stage in renal transplantation and are now widely recognized as the first cause of allograft failure. Diagnosis of antibody-mediated rejection has considerably improved with identification of antibody-mediated lesions in graft biopsies and advances made in the detection of circulating donor-specific antibodies. Unfortunately, this progress has not yet translated into better outcomes for patients. Indeed, in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction. This review provides an overview of the current knowledge of antibody-mediated rejection and discusses future interesting research directions.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of antibody-mediated rejection pathophysiologyMechanisms of action of therapies are indicated. Therapies currently used are in bold red; drugs under evaluation are in dashed orange. AMR, antibody-mediated rejection; Conv, convertase; IV, intravenous; MAC, membrane attack complex; MHC, major histocompatibility complex; mTOR, mammalian target of rapamycin; NK, natural killer.
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fig-001: Schematic representation of antibody-mediated rejection pathophysiologyMechanisms of action of therapies are indicated. Therapies currently used are in bold red; drugs under evaluation are in dashed orange. AMR, antibody-mediated rejection; Conv, convertase; IV, intravenous; MAC, membrane attack complex; MHC, major histocompatibility complex; mTOR, mammalian target of rapamycin; NK, natural killer.

Mentions: Recent experimental studies have shed light on the natural history of antibody-mediated rejection (AMR) (Figure 1) [12,13]. The sequence starts with the generation of antibodies directed against the graft (DSAs). Although highly polymorphic mismatched HLA molecules represent the most documented targets for DSAs, it is clear that DSAs can also be directed against other kinds of molecular targets, including polymorphic minor histocompatibility antigens [14] and, following a breakdown of B-cell tolerance [15], non-polymorphic autoantigens [16]. Although some studies suggest that “non-HLA” antibodies could participate in the development of rejection [17], particularly those expressed on the endothelial cell surface [18], such as anti-angiotensin II type-1 receptor antibodies [19,20], their exact pathological potential remains a matter of debate, and hereafter, we will focus on anti-donor HLA antibodies (abbreviated DSAs).


Recent advances in renal transplantation: antibody-mediated rejection takes center stage.

Pouliquen E, Koenig A, Chen CC, Sicard A, Rabeyrin M, Morelon E, Dubois V, Thaunat O - F1000Prime Rep (2015)

Schematic representation of antibody-mediated rejection pathophysiologyMechanisms of action of therapies are indicated. Therapies currently used are in bold red; drugs under evaluation are in dashed orange. AMR, antibody-mediated rejection; Conv, convertase; IV, intravenous; MAC, membrane attack complex; MHC, major histocompatibility complex; mTOR, mammalian target of rapamycin; NK, natural killer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4447042&req=5

fig-001: Schematic representation of antibody-mediated rejection pathophysiologyMechanisms of action of therapies are indicated. Therapies currently used are in bold red; drugs under evaluation are in dashed orange. AMR, antibody-mediated rejection; Conv, convertase; IV, intravenous; MAC, membrane attack complex; MHC, major histocompatibility complex; mTOR, mammalian target of rapamycin; NK, natural killer.
Mentions: Recent experimental studies have shed light on the natural history of antibody-mediated rejection (AMR) (Figure 1) [12,13]. The sequence starts with the generation of antibodies directed against the graft (DSAs). Although highly polymorphic mismatched HLA molecules represent the most documented targets for DSAs, it is clear that DSAs can also be directed against other kinds of molecular targets, including polymorphic minor histocompatibility antigens [14] and, following a breakdown of B-cell tolerance [15], non-polymorphic autoantigens [16]. Although some studies suggest that “non-HLA” antibodies could participate in the development of rejection [17], particularly those expressed on the endothelial cell surface [18], such as anti-angiotensin II type-1 receptor antibodies [19,20], their exact pathological potential remains a matter of debate, and hereafter, we will focus on anti-donor HLA antibodies (abbreviated DSAs).

Bottom Line: Unfortunately, this progress has not yet translated into better outcomes for patients.Indeed, in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction.This review provides an overview of the current knowledge of antibody-mediated rejection and discusses future interesting research directions.

View Article: PubMed Central - PubMed

Affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Transplantation, Néphrologie et Immunologie Clinique Lyon France ; Institut National de la Santé et de la Recherche Médicale U1111, Lyon France ; Unité de Formation et de Recherche Lyon Est, Université de Lyon Lyon France.

ABSTRACT
Overlooked for decades, antibodies have taken center stage in renal transplantation and are now widely recognized as the first cause of allograft failure. Diagnosis of antibody-mediated rejection has considerably improved with identification of antibody-mediated lesions in graft biopsies and advances made in the detection of circulating donor-specific antibodies. Unfortunately, this progress has not yet translated into better outcomes for patients. Indeed, in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction. This review provides an overview of the current knowledge of antibody-mediated rejection and discusses future interesting research directions.

No MeSH data available.


Related in: MedlinePlus