Exploring the single-cell immune landscape of kidney allograft inflammation using imaging mass cytometry

Alexander, Mariam P.; Zaidi, Mark; Larson, Nicholas; Mullan, Aidan; Pavelko, Kevin D.; Stegall, Mark D.; Bentall, Andrew; Wouters, Bradly G.; McKee, Trevor; Taner, Timucin

doi:10.1016/j.ajt.2023.11.008

Cited by 8 publications

(4 citation statements)

References 44 publications

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“…Besides alloreactive B cells, autoreactive and polyreactive B-cell infiltrates are found in the adventitia of arteries with TV in cardiac allografts, suggesting a role for autoantibodies in transplant rejection (9). Interestingly, CD19+ B cells are specifically associated with arteries, in kidney allograft biopsies, independently on the rejection phenotype, as recently shown using spatial transcriptomics (35). Antibodyindependent functions have also been highlighted, as B cells can provide help to alloreactive T cells (36) or could participate in maintaining an inflammatory milieu within the graft (37).…”

Section: Discussionmentioning

confidence: 69%

A minor tweak in transplant surgery protocols alters the cellular landscape of the arterial wall during transplant vasculopathy

Mickiewicz,

Zahreddine,

Cormier

et al. 2024

Front. Transplant.

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IntroductionTransplant vasculopathy (TV) is a major complication after solid organ transplantation, distinguished by an arterial intimal thickening that obstructs the vascular lumen and leads to organ rejection. To date, TV remains largely untreatable, mainly because the processes involved in its development remain unclear. Aortic transplantation in mice, used to mimic TV, relies on highly variable experimental protocols, particularly regarding the type of anastomosis used to connect the donor aorta to the recipient. While the amount of trauma undergone by a vessel can dramatically affect the resulting pathology, the impact of the type of anastomosis on TV in mice has not been investigated in detail.MethodsIn this study, we compare the cellular composition of aortic grafts from BALB/C donor mice transplanted into C57BL/6J recipient mice using two different anastomosis strategies: sleeve and cuff.ResultsWhile both models recapitulated some aspects of human TV, there were striking differences in the cellular composition of the grafts. Indeed, aortic grafts from the cuff group displayed a larger coverage of the neointimal area by vascular smooth muscle cells compared to the sleeve group. Aortic grafts from the sleeve group contained higher amounts of T cells, while the cuff group displayed larger B-cell infiltrates.DiscussionTogether, these data indicate that a seemingly minor technical difference in transplant surgery protocols can largely impact the cellular composition of the graft, and thus the mechanisms underlying TV after aortic transplantation in mice.

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Section: Discussionmentioning

confidence: 69%

A minor tweak in transplant surgery protocols alters the cellular landscape of the arterial wall during transplant vasculopathy

Mickiewicz,

Zahreddine,

Cormier

et al. 2024

Front. Transplant.

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“…We are hopeful that future Banff iterations will leverage digital pathology, artificial intelligence and machine learning tools to permit us to navigate from a categorical classification to a more meaningful, consistent, reproducible, auditable, and continuous scoring system ( 35 , 36 ). Finally, using novel diagnostic tools such as imaging mass cytometry ( 37 ) allows an unprecedented characterization of the immune composition with spatially enriched analysis, providing well-defined targets for personalized therapy.…”

Section: Considerations For Outcome Assessmentmentioning

confidence: 99%

“…Innovative single cell RNA sequencing and multiplex imaging for transcriptomic and spatial profiling of allograft tissue from patients experiencing different rejection phenotypes are also now available for investigational use. These revolutionary technologies can advance our understanding of the mechanisms of disease because they can help us understand heterogenous immune cell populations in ABMR ( 37 ). Spatial profiling has been performed using imaging mass cytometry ( 37 ), multiple iterative labeling by antibody neodeposition ( 50 ), and the GeoMX digital space profiling platform ( 51 ).…”

Section: Considerations For Outcome Assessmentmentioning

confidence: 99%

“…These revolutionary technologies can advance our understanding of the mechanisms of disease because they can help us understand heterogenous immune cell populations in ABMR ( 37 ). Spatial profiling has been performed using imaging mass cytometry ( 37 ), multiple iterative labeling by antibody neodeposition ( 50 ), and the GeoMX digital space profiling platform ( 51 ). The studies have highlighted the heterogeneity of the immune landscape and correlated these changes to the kidney microstructures.…”

Section: Considerations For Outcome Assessmentmentioning

confidence: 99%

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Challenges and opportunities for designing clinical trials for antibody mediated rejection

Balakrishnan,

Alexander,

Schinstock

2024

Front. Transplant.

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Significant progress has been made in kidney transplantation, with 1-year graft survival nearing 95%. However, long-term allograft survival remains suboptimal, with a 10-year overall graft survival rate of only 53.6% for deceased donor transplant recipients. Chronic active antibody-mediated rejection (ABMR) is a leading cause of death-censored graft loss, yet no therapy has demonstrated efficacy in large, randomized trials, despite substantial investment from pharmaceutical companies. Several clinical trials aimed to treat chronic ABMR in the past decade have yielded disappointing results or were prematurely terminated, attributed to factors including incomplete understanding of disease mechanisms, heterogeneous patient populations with comorbidities, slow disease progression, and limited patient numbers. This review aims to discuss opportunities for improving retrospective and prospective studies of ABMR, focusing on addressing heterogeneity, outcome measurement, and strategies to enhance patient enrollment to inform study design, data collection, and reporting.

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The CD8+ T cell content of transbronchial biopsies from patients with a first episode of clinically stable grade A1 cellular rejection is associated with future chronic lung allograft dysfunction

Beber,

Moshkelgosha,

White

et al. 2024

The Journal of Heart and Lung Transplantation

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Exploring the single-cell immune landscape of kidney allograft inflammation using imaging mass cytometry

Cited by 8 publications

References 44 publications

A minor tweak in transplant surgery protocols alters the cellular landscape of the arterial wall during transplant vasculopathy

A minor tweak in transplant surgery protocols alters the cellular landscape of the arterial wall during transplant vasculopathy

Challenges and opportunities for designing clinical trials for antibody mediated rejection

The CD8+ T cell content of transbronchial biopsies from patients with a first episode of clinically stable grade A1 cellular rejection is associated with future chronic lung allograft dysfunction

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