Changes in T and B cell subsets in end stage renal disease patients before and after kidney transplantation

Wang, Lei; Rondaan, Christien; Joode, Anoek A. E. de; Raveling-Eelsing, Elisabeth; Bos, Nicolaas; Westra, Johanna

doi:10.1186/s12979-021-00254-9

Cited by 10 publications

(11 citation statements)

References 39 publications

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“…End-stage renal disease (ESRD) is one of the major causes of concern for human health. At present, the most effective treatment is renal transplantation, however, rejection remains a major threat and is a primary independent risk factor affecting the long-term survival of the transplanted kidney ( 1 , 2 ). In addition, cABMR is a serious threat to the long-term survival of the transplanted kidney which needs attention ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptome Analysis of Chronic Antibody-Mediated Rejection After Renal Transplantation

Kong

Zhong

et al. 2022

Front. Immunol.

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Renal transplantation is currently the most effective treatment for end-stage renal disease. However, chronic antibody-mediated rejection (cABMR) remains a serious obstacle for the long-term survival of patients with renal transplantation and a problem to be solved. At present, the role and mechanism underlying immune factors such as T- and B- cell subsets in cABMR after renal transplantation remain unclear. In this study, single-cell RNA sequencing (scRNA-seq) of peripheral blood monocytes (PBMCs) from cABMR and control subjects was performed to define the transcriptomic landscape at single-cell resolution. A comprehensive scRNA-seq analysis was performed. The results indicated that most cell types in the cABMR patients exhibited an intense interferon response and release of proinflammatory cytokines. In addition, we found that the expression of MT-ND6, CXCL8, NFKBIA, NFKBIZ, and other genes were up-regulated in T- and B-cells and these genes were associated with pro-inflammatory response and immune regulation. Western blot and qRT-PCR experiments also confirmed the up-regulated expression of these genes in cABMR. GO and KEGG enrichment analyses indicated that the overexpressed genes in T- and B-cells were mainly enriched in inflammatory pathways, including the TNF, IL-17, and Toll-like receptor signaling pathways. Additionally, MAPK and NF-κB signaling pathways were also involved in the occurrence and development of cABMR. This is consistent with the experimental results of Western blot. Trajectory analysis assembled the T-cell subsets into three differentiation paths with distinctive phenotypic and functional prog rams. CD8 effector T cells and γδ T cells showed three different differentiation trajectories, while CD8_MAI T cells and naive T cells primarily had two differentiation trajectories. Cell-cell interaction analysis revealed strong T/B cells and neutrophils activation in cABMR. Thus, the study offers new insight into pathogenesis and may have implications for the identification of novel therapeutic targets for cABMR.

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Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptome Analysis of Chronic Antibody-Mediated Rejection After Renal Transplantation

Kong

Zhong

et al. 2022

Front. Immunol.

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“…Therefore, the decrease in the ratio of B cells to CD28-CD8+ T cells and the increase in the ratio of CD28-CD8+ T cells to Tregs can be explained at least in part by the increase in CD28-CD8+ T cells. On the other hand, the association between B cell frequency and CMV status is less well-documented ( 29 , 31 ). The effect of CMV on lymphocyte phenotypes in transplant recipients is an interesting issue necessitating further research but is beyond the scope of this paper.…”

Section: Resultsmentioning

confidence: 99%

“…We found that compared to the CMV group 0, the other groups had a significant decrease in B cell percentage (Tables 2, 3), a significant decrease in the ratio of B cells to CD28- CD8+ T cells (Tables 4, 5), and a significant increase in the ratio of CD28-CD8+ T cells to Tregs (Tables 6, 7). Several recent studies have shown that kidney transplant patients with positive CMV serology have higher frequency of CD28-CD8+ T cells compared to those with negative CMV serology (28)(29)(30). Therefore, the decrease in the ratio of B cells to CD28-CD8+ T cells and the increase in the ratio of CD28-CD8+ T cells to Tregs can be explained at least in part by the increase in CD28-CD8+ T cells.…”

Section: Rejection Of All Types Is Associated With An Increase In The...mentioning

confidence: 99%

Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies

Degauque

Lorent

et al. 2023

Front. Immunol.

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IntroductionThe human immune system contains cells with either effector/memory or regulatory functions. Besides the well-established CD4+CD25hiCD127lo regulatory T cells (Tregs), we and others have shown that B cells can also have regulatory functions since their frequency and number are increased in kidney graft tolerance and B cell depletion as induction therapy may lead to acute rejection. On the other hand, we have shown that CD28-CD8+ T cells represent a subpopulation with potent effector/memory functions. In the current study, we tested the hypothesis that kidney allograft rejection may be linked to an imbalance of effector/memory and regulatory immune cells.MethodsBased on a large cohort of more than 1000 kidney graft biopsies with concomitant peripheral blood lymphocyte phenotyping, we investigated the association between kidney graft rejection and the percentage and absolute number of circulating B cells, Tregs, as well as the ratio of B cells to CD28-CD8+ T cells and the ratio of CD28-CD8+ T cells to Tregs. Kidney graft biopsies were interpreted according to the Banff classification and divided into 5 biopsies groups: 1) normal/subnormal, 2) interstitial fibrosis and tubular atrophy grade 2/3 (IFTA), 3) antibody-mediated rejection (ABMR), 4) T cell mediated-rejection (TCMR), and 5) borderline rejection. We compared group 1 with the other groups as well as with a combined group 3, 4, and 5 (rejection of all types) using multivariable linear mixed models.Results and discussionWe found that compared to normal/subnormal biopsies, rejection of all types was marginally associated with a decrease in the percentage of circulating B cells (p=0.06) and significantly associated with an increase in the ratio of CD28-CD8+ T cells to Tregs (p=0.01). Moreover, ABMR, TCMR (p=0.007), and rejection of all types (p=0.0003) were significantly associated with a decrease in the ratio of B cells to CD28-CD8+ T cells compared to normal/subnormal biopsies. Taken together, our results show that kidney allograft rejection is associated with an imbalance between immune cells with effector/memory functions and those with regulatory properties.

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“…This leads to an altered immunological landscape in SOT recipients, resulting in differing host responses to severe infections, including from SARS-CoV-2. SOT recipients at baseline have decreased frequencies of circulating naïve T and NK cells, and an increased frequency of terminally differentiated and senescent T cells compared with the general population [11][12][13] . Few studies, however, have pro led the immune landscape of SOT recipients in the context of severe infection, and none have yet used a multi-omic approach to assess their responses at the cellular, protein, transcriptional, and microbial levels.…”

Section: Introductionmentioning

confidence: 97%

Host-Microbe Multi-omic Profiling Identifies a Unique Program of COVID-19 Inflammatory Dysregulation in Solid Organ Transplant Recipients

Langelier,

Pickering,

Schaenman

et al. 2023

Preprint

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Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant (SOT) recipients, who have atypical but poorly characterized immune responses to SARS-CoV-2 infection. We sought to understand the host immunologic and microbial features of COVID-19 in SOT recipients by leveraging a prospective multicenter cohort of 1164 hospitalized patients. Using multi-omic immuoprofiling, we studied 86 SOT recipients in this cohort, who were age- and sex-matched 2:1 with 172 non-SOT controls. PBMC and nasal transcriptional profiling unexpectedly demonstrated upregulation of innate immune pathways related to interferon (IFN) and Toll-like receptor signaling, and complement activation, in SOT recipients. Longitudinal analyses across the first 30-days post-hospitalization demonstrated persistent upregulation of these innate immunity pathways in SOT recipients. The levels of several proinflammatory serum chemokines, such as CX3CL1 and KITLG, were also higher in SOT recipients at the time of hospitalization, although IFN-gamma levels were lower. We observed differential dynamics of CXCL11, which remained persistently elevated in SOT recipients over the course of hospitalization. Nasal microbiome alpha diversity was higher in SOT recipients versus controls, but no differences in taxonomic abundance beyond SARS-CoV-2 were observed. SOT recipients had higher nasal SARS-CoV-2 viral loads and impaired viral clearance compared to controls. Antibody analysis demonstrated lower anti-SARS-CoV-2 spike IgG levels in SOT recipients upon hospitalization, but no distinctions over time compared to controls. Mass cytometry demonstrated marked differences in blood immune cell populations, with SOT recipients exhibiting decreased plasmablasts and transitional B cells, and increased senescent T cells. Severe disease in SOT recipients was characterized by a less robust induction of inflammatory chemokines, such as IL-6 and CCL7, and a more subtle proinflammatory transcriptional response in the blood and airway. Together, our study reveals distinct immune features and altered viral dynamics in SOT recipients compared to non-SOT controls. We unexpectedly find that SOT recipients exhibit an augmented, predominantly innate immune response in both the blood and upper respiratory tract that remains relatively stable across disease severity, in contrast to non-SOT controls. These findings may relate to the paradoxical observation that SOT recipients have similar COVID-19 mortality rates versus the general population, despite being more susceptible to SARS-CoV-2 infection, remaining infectious longer, and having higher rates of hospitalization. In summary, we find that COVID-19 in SOT recipients is characterized by a biologically distinct immune state, suggesting the potential for unique prognostic biomarkers and therapeutic approaches in this vulnerable population.

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Changes in T and B cell subsets in end stage renal disease patients before and after kidney transplantation

Cited by 10 publications

References 39 publications

Single-Cell Transcriptome Analysis of Chronic Antibody-Mediated Rejection After Renal Transplantation

Single-Cell Transcriptome Analysis of Chronic Antibody-Mediated Rejection After Renal Transplantation

Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies

Host-Microbe Multi-omic Profiling Identifies a Unique Program of COVID-19 Inflammatory Dysregulation in Solid Organ Transplant Recipients

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