Novel therapeutic opportunities afforded by plasma cell biology in transplantation

Agarwal, Divyansh; Allman, David; Naji, Ali

doi:10.1111/ajt.15813

Cited by 11 publications

(7 citation statements)

References 73 publications

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“…5,6 Corticosteroid, plasmapheresis, IV immunoglobulin, and rituximab have been insufficient to eradicate these antibodies, prompting the development of several new agents. 7 Greater insight into the biology underlying formation and maintenance of HLA antibodies is critical to therapy development and understanding their mechanisms of action and failure.…”

Section: Introductionmentioning

confidence: 99%

“…MBCs are long lived and can regenerate or differentiate into PCs. 7 Most early PCs die within weeks of an initial immune response. However, some PCs may be spared, becoming long-lived PCs (LLPCs) that survive for years to decades.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 The factors that determine whether LLPCs are formed are incompletely understood, particularly in humans. 7 MBCs alone may be sufficient to sustain long-lived responses. 10 Alternatively, antibody responses may be maintained by the combination of MBCs and LLPCs.…”

Section: Introductionmentioning

confidence: 99%

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Stable HLA antibodies following sustained CD19+ cell depletion implicate a long-lived plasma cell source

Zhang

Schuster

Lacey³

et al. 2020

Blood Advances

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stable HLA antibodies following sustained CD19+ cell depletion implicate a long-lived plasma cell source

Zhang

Schuster

Lacey³

et al. 2020

Blood Advances

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“…With the renaissance of immunomodulatory therapies, novel desensitization protocols seek to increase access to transplantation for the immunologically disadvantaged group of HLA‐sensitized individuals 40 . BLyS is a potent survival cytokine for B‐cells, and it has been hypothesized that specifically antagonizing BLyS might suppress anti‐HLA Ab production, and increase the function of the potentially tolerogenic regulatory B‐cells 41,42 .…”

Section: Discussionmentioning

confidence: 99%

Adaptation of HLA testing to characterize the cynomolgus macaque MHC polymorphisms and alloantibody signatures

Agarwal,

Liu,

Bhoj

et al. 2023

HLA

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Nonhuman primates are the closest animal models to humans with respect to genetics and physiology. Consequently, a critical component of immunogenetics research relies on drawing inferences from the cynomolgus macaque to inform human trials. Despite the conserved organization of the Major Histocompatibility Complex (MHC) between cynomolgus macaques and humans, MHC genotyping of cynomolgus macaques is challenging due to high rates of copy number variants, duplications, and rearrangements, particularly at the MHC class I loci. Furthermore, the limited availability of commercial reagents specific to cynomolgus macaques that can be used to characterize anti‐MHC class I and class II antibody (Ab) specificities in cynomolgus macaques presents a major bottleneck in translational research. Here we successfully characterized cynomolgus macaque Mafa class I and class II serologic specificities in 86 animals originating from various geographical regions using the complement dependent cytotoxicity (CDC) assay with human HLA class I and class II monoclonal antibody (mAb) typing trays. Further, we successfully induced and characterized anti‐Mafa class I and class II alloantibody specificity using HLA single antigen bead assays. We also subsequently tracked the alloAb burden in the animals during treatment with anti‐B lymphocyte stimulator (BLyS) treatment. Altogether, these methods can be easily used in translational research to serotype MHC class I and class II specificity in macaques, characterize their alloAb specificity, and evaluate the efficacy of novel therapeutic modalities in depleting circulating alloAbs in these animals.

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“…Belimumab is a monoclonal antibody targeting the cytokine B lymphocyte stimulator (BLyS) critical for B lymphocyte survival. As such, it has been proposed to limit plasma cell survival and could thus reduce humoral alloimmunity ( 113 ). In animal studies, BLyS inhibition resulted in DSA reduction and prolonged graft survival ( 114 , 115 ).…”

Section: Strategies For Amr Treatment and Dsa Reductionmentioning

confidence: 99%

B Cell Immunity in Lung Transplant Rejection - Effector Mechanisms and Therapeutic Implications

Ohm

Jungraithmayr

2022

Front. Immunol.

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Allograft rejection remains the major hurdle in lung transplantation despite modern immunosuppressive treatment. As part of the alloreactive process, B cells are increasingly recognized as modulators of alloimmunity and initiators of a donor-specific humoral response. In chronically rejected lung allografts, B cells contribute to the formation of tertiary lymphoid structures and promote local alloimmune responses. However, B cells are functionally heterogeneous and some B cell subsets may promote alloimmune tolerance. In this review, we describe the current understanding of B-cell-dependent mechanisms in pulmonary allograft rejection and highlight promising future strategies that employ B cell-targeted therapies.

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Novel therapeutic opportunities afforded by plasma cell biology in transplantation

Cited by 11 publications

References 73 publications

Stable HLA antibodies following sustained CD19+ cell depletion implicate a long-lived plasma cell source

Stable HLA antibodies following sustained CD19+ cell depletion implicate a long-lived plasma cell source

Adaptation of HLA testing to characterize the cynomolgus macaque MHC polymorphisms and alloantibody signatures

B Cell Immunity in Lung Transplant Rejection - Effector Mechanisms and Therapeutic Implications

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