Novel strategies to target the humoral alloimmune response

Suchánek, Ondřej; Clatworthy, Menna R.

doi:10.1111/tan.14092

Cited by 11 publications

(5 citation statements)

References 135 publications

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“…DSA target graft cells, resulting in complement activation and inflammatory reactions with the recruitment and activation of neutrophils. These phenomena induce graft tissue damage ( Suchanek and Clatworthy, 2020 ; Oellerich et al., 2021 ) ( Figure 2 ).…”

Section: Graft Rejection Mechanismsmentioning

confidence: 99%

Solid organ transplantation and gut microbiota: a review of the potential immunomodulatory properties of short-chain fatty acids in graft maintenance

Jardou,

Brossier,

Marquet

et al. 2024

Front. Cell. Infect. Microbiol.

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Transplantation is the treatment of choice for several end-stage organ defects: it considerably improves patient survival and quality of life. However, post-transplant recipients may experience episodes of rejection that can favor or ultimately lead to graft loss. Graft maintenance requires a complex and life-long immunosuppressive treatment. Different immunosuppressive drugs (i.e., calcineurin inhibitors, glucocorticoids, biological immunosuppressive agents, mammalian target of rapamycin inhibitors, and antiproliferative or antimetabolic agents) are used in combination to mitigate the immune response against the allograft. Unfortunately, the use of these antirejection agents may lead to opportunistic infections, metabolic (e.g., post-transplant diabetes mellitus) or cardiovascular (e.g., arterial hypertension) disorders, cancer (e.g., non-Hodgkin lymphoma) and other adverse effects. Lately, immunosuppressive drugs have also been associated with gut microbiome alterations, known as dysbiosis, and were shown to affect gut microbiota-derived short-chain fatty acids (SCFA) production. SCFA play a key immunomodulatory role in physiological conditions, and their impairment in transplant patients could partly counterbalance the effect of immunosuppressive drugs leading to the activation of deleterious pathways and graft rejection. In this review, we will first present an overview of the mechanisms of graft rejection that are prevented by the immunosuppressive protocol. Next, we will explain the dynamic changes of the gut microbiota during transplantation, focusing on SCFA. Finally, we will describe the known functions of SCFA in regulating immune-inflammatory reactions and discuss the impact of SCFA impairment in immunosuppressive drug treated patients.

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Section: Graft Rejection Mechanismsmentioning

confidence: 99%

Solid organ transplantation and gut microbiota: a review of the potential immunomodulatory properties of short-chain fatty acids in graft maintenance

Jardou,

Brossier,

Marquet

et al. 2024

Front. Cell. Infect. Microbiol.

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“…De novo generation of DSAs is a consequence of naïve B cell activation following alloantigen recognition via B cell receptor (BCR). Alloreactive B cells can either differentiate into short-lived (extrafollicular) plasma cells or contribute to memory compartment residing in germinal centers (GC) of lymph nodes [ 110 ]. Extrafollicular plasmablasts are the source of low-affinity IgM antibodies.…”

Section: Sev In Solid Organ Transplantationmentioning

confidence: 99%

Small Extracellular Vesicles in Transplant Rejection

Gołębiewska

Wardowska

Pietrowska

et al. 2021

Cells

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Small extracellular vesicles (sEV), which are released to body fluids (e.g., serum, urine) by all types of human cells, may stimulate or inhibit the innate and adaptive immune response through multiple mechanisms. Exosomes or sEV have on their surface many key receptors of immune response, including major histocompatibility complex (MHC) components, identical to their cellular origin. They also exhibit an ability to carry antigen and target leukocytes either via interaction with cell surface receptors or intracellular delivery of inflammatory mediators, receptors, enzymes, mRNAs, and noncoding RNAs. By the transfer of donor MHC antigens to recipient antigen presenting cells sEV may also contribute to T cell allorecognition and alloresponse. Here, we review the influence of sEV on the development of rejection or tolerance in the setting of solid organ and tissue allotransplantation. We also summarize and discuss potential applications of plasma and urinary sEV as biomarkers in the context of transplantation. We focus on the attempts to use sEV as a noninvasive approach to detecting allograft rejection. Preliminary studies show that both sEV total levels and a set of specific molecules included in their cargo may be an evidence of ongoing allograft rejection.

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“…27 Moreover, systemic inflammation is accompanied by immune activation that may promote the production of de novo DSA. For example, among many effects, IL-6 is essential for B cell differentiation, antibody production and the generation of long-lived plasma cells 28,29 Previously, we have shown that pre-existing chronic systemic inflammation at the time of transplantation predicts delayed graft function and all-cause mortality in kidney transplanted recipients. 30 In the present study, our ambition was to explore mechanisms that link systemic inflammation at the time of transplantation with mortality in the following years.…”

Section: Introductionmentioning

confidence: 99%

“… 27 Moreover, systemic inflammation is accompanied by immune activation that may promote the production of de novo DSA. For example, among many effects, IL‐6 is essential for B cell differentiation, antibody production and the generation of long‐lived plasma cells 28 , 29 …”

Section: Introductionmentioning

confidence: 99%

Pretransplant serum levels of endothelial cell activation markers are associated with graft loss and mortality after kidney transplantation

et al. 2022

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Long‐term allograft survival remains a challenge in kidney transplantation. In this study, we aimed to identify biomarkers for potentially modifiable pathways involved in the outcome of kidney transplantation. We tested the hypothesis that a pre‐existing systemic environment with endothelial cell activation in the recipient is associated with the outcome after kidney transplantation. In a retrospective study cohort of 611 kidney transplanted patients, we investigated associations between serum levels of soluble intercellular adhesion molecule‐1 (sICAM‐1) and soluble vascular cell adhesion molecule‐1 (sVCAM‐1) before transplantation and delayed graft function, acute rejection, graft loss and mortality after transplantation. We adjusted associations for age, sex, preformed donor‐specific antibodies (DSA), pretransplant diabetes, cardiovascular disease and dialysis. Additionally, we investigated if associations between endothelial cell activation markers and outcomes differed in recipients with and without preformed DSA. Serum levels of endothelial cell activation markers were associated with delayed graft function and mortality but not with rejection. Additionally, high levels of sICAM‐1 were associated with graft loss. Associations were most pronounced in recipients without DSA, adjusted for potential confounders. Data suggest that endothelial cell activation at the time of transplantation is associated with graft loss and mortality after kidney transplantation, especially in transplant candidates without preformed DSA.

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Novel strategies to target the humoral alloimmune response

Cited by 11 publications

References 135 publications

Solid organ transplantation and gut microbiota: a review of the potential immunomodulatory properties of short-chain fatty acids in graft maintenance

Solid organ transplantation and gut microbiota: a review of the potential immunomodulatory properties of short-chain fatty acids in graft maintenance

Small Extracellular Vesicles in Transplant Rejection

Pretransplant serum levels of endothelial cell activation markers are associated with graft loss and mortality after kidney transplantation

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