Effect of C1q-binding donor-specific anti-HLA antibodies on the clinical outcomes of patients after renal transplantation: A systematic review and meta-analysis

Kang, Zhong-Yu; Li, Chun; Liu, Wei; Li, Dai‐Hong

doi:10.1016/j.trim.2022.101566

Cited by 7 publications

(5 citation statements)

References 48 publications

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“…This is consistent with what has been found in previous papers [ 25 , 26 ]. A recent meta-analysis by Kang et al, which included relevant studies comparing the clinical outcomes between DSA C1q (+) and DSA C1q (−) kidney transplant recipients, demonstrated that C1q-binding DSAs are associated with increased risks of ABMR, renal allograft failure, and patient death [ 48 ]. The pathogenic potential of C1q DSA is explained by the fact that binding complement fraction C1 is the first step in the activation of the classic complement pathway, which results in the formation of a membrane attack complex that contributes to vascular injury and causes target cell damage [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Association of Circulating Anti-HLA Donor-Specific Antibodies and Their Characteristics, including C1q-Binding Capacity, in Kidney Transplant Recipients with Long-Term Renal Graft Outcomes

Gniewkiewicz

Czerwińska

Zielniok

et al. 2023

JCM

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Post-transplant antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) monitoring in kidney transplant recipients remains unclear and is currently under investigation. The pathogenicity of anti-HLA DSAs is determined by antibody classes, specificity, mean fluorescent intensity (MFI), C1q-binding capacity, and IgG subclasses. The aim of this study was to investigate the association of circulating DSAs and their characteristics with renal allograft long-term outcomes. The study included 108 consecutive patients from our transplant center who underwent kidney allograft biopsy between November 2018 and November 2020, 3 to 24 months after kidney transplantation. At the time of biopsy, patients’ sera were collected for analysis of anti-HLA DSAs. Patients were followed for a median time of 39.0 months (Q1–Q3, 29.8–45.0). Detection of anti-HLA DSAs at the time of biopsy (HR = 5.133, 95% CI 2.150–12.253, p = 0.0002) and their C1q-binding capacity (HR = 14.639, 95% CI 5.320–40.283, p ≤ 0.0001) were independent predictors of the composite of sustained 30% reduction from estimated glomerular filtration rate or death-censored graft failure. Identification of anti-HLA DSAs and their C1q-binding capacity could be useful in identifying kidney transplant recipients at risk for inferior renal allograft function and graft failure. Analysis of C1q is noninvasive, accessible, and should be considered in clinical practice in post-transplant monitoring.

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Section: Discussionmentioning

confidence: 99%

Association of Circulating Anti-HLA Donor-Specific Antibodies and Their Characteristics, including C1q-Binding Capacity, in Kidney Transplant Recipients with Long-Term Renal Graft Outcomes

Gniewkiewicz

Czerwińska

Zielniok

et al. 2023

JCM

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“…Identifying prognosis-related factors in the donor’s kidney during the pre-transplant stage. For example, the available evidence suggests an association between donor-specific antibodies and poor KTx outcomes [ 7 , 67 ]. Furthermore, exploring the impact of pre-donor and pre-transplant therapy on the renal allograft.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential necroinflammation-associated necroptosis-related biomarkers for delayed graft function and renal allograft failure: a machine learning-based exploration in the framework of predictive, preventive, and personalized medicine

Qiu

et al. 2023

EPMA Journal

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Delayed graft function (DGF) is one of the key post-operative challenges for a subset of kidney transplantation (KTx) patients. Graft survival is significantly lower in recipients who have experienced DGF than in those who have not. Assessing the risk of chronic graft injury, predicting graft rejection, providing personalized treatment, and improving graft survival are major strategies for predictive, preventive, and personalized medicine (PPPM/3PM) to promote the development of transplant medicine. However, since PPPM aims to accurately identify disease by integrating multiple omics, current methods to predict DGF and graft survival can still be improved. Renal ischemia/reperfusion injury (IRI) is a pathological process experienced by all KTx recipients that can result in varying occurrences of DGF, chronic rejection, and allograft failure depending on its severity. During this process, a necroinflammation-mediated necroptosis-dependent secondary wave of cell death significantly contributes to post-IRI tubular cell loss. In this article, we obtained the expression matrices and corresponding clinical data from the GEO database. Subsequently, nine differentially expressed necroinflammation-associated necroptosis-related genes (NiNRGs) were identified by correlation and differential expression analysis. The subtyping of post-KTx IRI samples relied on consensus clustering; the grouping of prognostic risks and the construction of predictive models for DGF (the area under the receiver operating characteristic curve (AUC) of the internal validation set and the external validation set were 0.730 and 0.773, respectively) and expected graft survival after a biopsy (the internal validation set’s 1-year AUC: 0.770; 2-year AUC: 0.702; and 3-year AUC: 0.735) were based on the least absolute shrinkage and selection operator regression algorithms. The results of the immune infiltration analysis showed a higher infiltration abundance of myeloid immune cells, especially neutrophils, macrophages, and dendritic cells, in the cluster A subtype and prognostic high-risk groups. Therefore, in the framework of PPPM, this work provides a comprehensive exploration of the early expression landscape, related pathways, immune features, and prognostic impact of NiNRGs in post-KTx patients and assesses their capabilities as. predictors of post-KTx DGF and graft loss, targets of the vicious loop between regulated tubular cell necrosis and necroinflammation for targeted secondary and tertiary prevention, and references for personalized immunotherapy. Supplementary Information The online version contains supplementary material available at 10.1007/s13167-023-00320-w.

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“…In these two pediatric studies, all patients with graft loss due to rejection had persistent C1q + DSA 34 . A 2022 meta‐analysis of 26 studies estimated that patients with C1q + DSA had a 2.4 times increased risk of graft failure (95% CI 1.66–3.47, p < .00001) and a 3.13 times increased risk of death (95% CI 1.06–9.23, p = .04) compared to those with C1q‐DSA 35 . While C1q testing is available for clinical practice, its overall utility remains controversial due to the strong association between C1q binding activity and MFI 36 or antibody titer, 37 and studies suggesting that C1q binding activity measurements can be affected by diluting or concentrating the serum samples 38 …”

Section: Donor‐specific Antibodiesmentioning

confidence: 99%

Immune monitoring in pediatric kidney transplant

Laroche,

Engen

2024

Pediatric Transplantation

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BackgroundLong‐term outcomes in pediatric kidney transplantation remain suboptimal, largely related to chronic rejection. Creatinine is a late marker of renal injury, and more sensitive, early markers of allograft injury are an active area of current research.MethodsThis is an educational review summarizing existing strategies for monitoring for rejection in kidney transplant recipients.ResultsWe summarize supporting currently available clinical tests, including surveillance biopsy, donor specific antibodies, and donor‐derived cell free DNA, as well as the potential limitations of these studies. In addition, we review the current avenues of active research, including transcriptomics, proteomics, metabolomics, and torque tenovirus levels.ConclusionAdvancing the use of noninvasive immune monitoring will depend on well‐designed multicenter trials that include patients with stable graft function, include biopsy results on all patients, and can demonstrate both association with a patient‐relevant clinical endpoint such as graft survival or change in glomerular filtration rate and a potential timepoint for intervention.

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Effect of C1q-binding donor-specific anti-HLA antibodies on the clinical outcomes of patients after renal transplantation: A systematic review and meta-analysis

Cited by 7 publications

References 48 publications

Association of Circulating Anti-HLA Donor-Specific Antibodies and Their Characteristics, including C1q-Binding Capacity, in Kidney Transplant Recipients with Long-Term Renal Graft Outcomes

Association of Circulating Anti-HLA Donor-Specific Antibodies and Their Characteristics, including C1q-Binding Capacity, in Kidney Transplant Recipients with Long-Term Renal Graft Outcomes

Identification of potential necroinflammation-associated necroptosis-related biomarkers for delayed graft function and renal allograft failure: a machine learning-based exploration in the framework of predictive, preventive, and personalized medicine

Immune monitoring in pediatric kidney transplant

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