Cell mediated rejection revisited: Past, current, and future directions

Hara, Shigeo

doi:10.1111/nep.13283

Cited by 8 publications

(4 citation statements)

References 54 publications

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“…Therefore, there is an urgent need for diagnostic molecule markers. As widely accepted, the occurrence of IF/TA is closely related to inflammation, and the inflammation in fibrosis areas (i)-IF/TA score which derived from the BANFF score is used to evaluate the degree of fibrosis after kidney transplantation [17]. Multiple inflammation interaction and related pathways consequently induced fibroblasts infiltration, which promotes the formation of extracellular matrix and irreversible fibrosis and ultimately leads to the loss of renal function [18].…”

Section: Discussionmentioning

confidence: 99%

The Potential Diagnostic Value of Immune-Related Genes in Interstitial Fibrosis and Tubular Atrophy after Kidney Transplantation

Yang

Shi

Chen

et al. 2022

Journal of Immunology Research

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Background. Inflammation within areas of interstitial fibrosis and tubular atrophy (IF/TA) is associated with kidney allograft failure. The aim of this study was to reveal new diagnostic markers of IF/TA based on bioinformatics analysis. Methods. Raw data of IF/TA samples after kidney transplantation and control samples after kidney transplantation were extracted from the Gene Expression Omnibus (GEO) database (GSE76882 and GSE120495 datasets), and genes that were differentially expressed between the two groups (DEGs) were screened. Gene Set Enrichment Analysis (GSEA), ESTIMATE and single sample GSEA (ssGSEA), least absolute shrinkage and selection operator (LASSO) regression analysis, and competing endogenous RNA (ceRNA) network were used to analyze the data. Results. The results of GSEA revealed that multiple immune-related pathways were enriched in the IF/TA group, and subsequent immune landscape analysis also showed that the IF/TA group had higher immune and stromal scores and up to 15 types of immune cells occupied them, such as B cells, cytotoxic cells, and T cells. LASSO regression analysis selected 6 (including ANGPTL3, APOH, LTF, FCGR2B, HLA-DQA2, and EGF) out of 14 DE-IRGs as diagnostic genes to construct a diagnostic model. Then, receiver operating characteristic (ROC) curve analysis showed the powerful diagnostic value of the model, and the area under the curve (AUC) of a single diagnostic gene was greater than 0.75. The results of ingenuity pathway analysis (IPA) also indicated that DEGs were involved in the immune system and kidney disease-related pathways. Finally, we found multiple miRNAs that could regulate diagnostic genes from the ceRNA network. Conclusion. This study identified 6 IF/TA-related genes, which might be used as a new diagnosis model in the clinical practice.

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Section: Discussionmentioning

confidence: 99%

The Potential Diagnostic Value of Immune-Related Genes in Interstitial Fibrosis and Tubular Atrophy after Kidney Transplantation

Yang

Shi

Chen

et al. 2022

Journal of Immunology Research

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“…However, serious pathology also arises when the immune system becomes “overstimulated” following infection (“postinfectious immunopathology”) or attacks normal self-antigens (autoimmunity). The rejection of a transplanted solid organ or bone marrow stem cells across a histocompatibility barrier (a different “tissue type”) is another setting in which cellular immunity results in adverse clinical outcomes . These disease states are typically treated with “broad spectrum” immune-suppressant drugs such as corticosteroids whose broad range of off-target effects cause considerable morbidity and some mortality .…”

Section: Introductionmentioning

confidence: 99%

“…The rejection of a transplanted solid organ or bone marrow stem cells across a histocompatibility barrier (a different “tissue type”) is another setting in which cellular immunity results in adverse clinical outcomes. 2 These disease states are typically treated with “broad spectrum” immune-suppressant drugs such as corticosteroids whose broad range of off-target effects cause considerable morbidity and some mortality. 3 New drugs that precisely target the immune mechanisms critical for a given pathology are desperately needed.…”

Section: Introductionmentioning

confidence: 99%

Small Molecule Inhibitors of Lymphocyte Perforin as Focused Immunosuppressants for Infection and Autoimmunity

et al. 2022

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New drugs that precisely target the immune mechanisms critical for cytotoxic T lymphocyte (CTL) and natural killer (NK) cell driven pathologies are desperately needed. In this perspective, we explore the cytolytic protein perforin as a target for therapeutic intervention. Perforin plays an indispensable role in CTL/NK killing and controls a range of immune pathologies, while being encoded by a single copy gene with no redundancy of function. An immunosuppressant targeting this protein would provide the first-ever therapy focused specifically on one of the principal cell death pathways contributing to allotransplant rejection and underpinning multiple autoimmune and postinfectious diseases. No drugs that selectively block perforin-dependent cell death are currently in clinical use, so this perspective will review published novel small molecule inhibitors, concluding with in vivo proof-of-concept experiments performed in mouse models of perforin-mediated immune pathologies that provide a potential pathway toward a clinically useful therapeutic agent.

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“…The juxtaposition between acute rejection rate reduction and lack of improvement in graft survival within the current era of immunosuppression was reproduced in an ANZDATA analysis of 4325 kidney transplants between 1997 and 2004 (43). While the rate of acute rejection within six months of transplantation decreased from 39% (95% CI [33][34][35][36][37][38][39][40][41][42][43][44][45] Multiple factors potentially contribute to the rejection-survival paradox. Functional recovery appears instrumental as grafts with persistent dysfunction post-rejection episode above their baseline function have attenuated survival, perhaps due to considerable structural damage causing reduced nephron reserve and/ or predisposing them to subsequent rejection episodes (8).…”

Section: Acute Rejection and Graft Loss Attrition Rates Was The Focusmentioning

confidence: 99%

Very early acute rejection in an Australian and New Zealand kidney transplant population

Putrino¹

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Background:Acute rejection is an important complication of kidney transplantation. Very early acute rejection (VEAR) is defined in this project as rejection during the first week post-transplant. This may have implications for transplant outcomes independent of those attributed to acute rejection (rejection within three months of transplantation). The worldwide trend observed since the end of the 20 th century in which graft survival rates have stagnated despite continued amelioration of acute rejection may be in part explained by VEAR. Aims:The aims of this project are: 1. To document the demographics of an Australian and New Zealand population receiving a kidney-alone transplant between 2004 and 2014 in terms of donor, recipient, and transplant process factors 2. To describe the epidemiology of acute rejection in this cohort 3. To describe characteristics of VEAR 4. To identify potential predictors of VEAR 5. To study the associations between VEAR and patient and graft survivals 6. To relate findings of the above to discordant trends between graft rejection and survival rates Materials and methods:This registry-based, retrospective observational cohort study included all adult recipients of kidneyalone grafts transplanted between 1 January 2004 and 31 December 2014 in Australia and New ii Zealand. VEAR was the primary outcome. Patient death, overall graft loss, and death-censored graft loss (DCGL) were secondary outcomes. Results:8405 kidney grafts were transplanted into 8260 recipients and followed for a median of 4.2 years.Many changes in practice occurred over the study period. Increasingly poorer quality donors were utilised as evidenced by a cohort that was progressively older (mean age 45.1±15.4 years in 2004 v 48.2±16.3 years in 2014; P<0.001), more likely to be affected by hypertension (18 v 21%; P<0.001), and with a higher kidney donor risk index for deceased donors (median 1.20 [0.87-1.53] v 1.29 [1.03-1.66]; P<0.01). Recipients were medically and immunologically more challenging with an increase in mean age (47±12.6 years in 2004 v 51±13.5 years in 2014; P<0.001), a greater burden of comorbidities, and a higher number of human leucocyte antigen (HLA) mismatches (proportion of grafts with five or six mismatches 29% v 37%; P<0.001). The overall rejection rate decreased from 30% in 2004 to 19% in 2014 (P<0.001) with a corresponding fall in VEAR from 8 to 6% (P<0.001). In contrast, there was no significant change in death-censored graft survival (DCGS) for either living (one-year survival 98.2 v 99.1%; P=0.80) or deceased (one-year survival 96.6 v 98.5%; P=0.56) donor grafts. Further investigation of the relationship between VEAR and the discordant rejection-survival paradigm was restricted due to limited information available in the registries. VEAR occurred in 183 of 3025 living donor grafts (6%) and 353 of 5380 deceased donor grafts (7%).Grafts complicated by VEAR were more likely than those without to be a repeat transplant, to have a higher or broader range of peak panel reactive antibody (PRA) and ...

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Cell mediated rejection revisited: Past, current, and future directions

Abstract: The updated version of the Banff 2017 scheme presents revised criteria of chronic active T-cell mediated rejection. This review encompasses recent advances in cell-mediated tissue injury in kidney allograft. Current perspectives on vascular lesions are also summarized.

Cited by 8 publications

References 54 publications

The Potential Diagnostic Value of Immune-Related Genes in Interstitial Fibrosis and Tubular Atrophy after Kidney Transplantation

The Potential Diagnostic Value of Immune-Related Genes in Interstitial Fibrosis and Tubular Atrophy after Kidney Transplantation

Small Molecule Inhibitors of Lymphocyte Perforin as Focused Immunosuppressants for Infection and Autoimmunity

Very early acute rejection in an Australian and New Zealand kidney transplant population

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