Potential urinary extracellular vesicle protein biomarkers of chronic active antibody-mediated rejection in kidney transplant recipients

Jung, Hee-Yeon; Lee, Chan-Hyeong; Choi, Ji-Young; Cho, Jang‐Hee; Park, Sun-Hee; Kim, Yong-Lim; Moon, Pyong-Gon; Baek, Moon‐Chang; Park, Jae Berm; Kim, Yeong Hoon; Chung, Byung Ha; Lee, Sang-Ho; Kim, Chan‐Duck

doi:10.1016/j.jchromb.2019.121958

Cited by 35 publications

(31 citation statements)

References 31 publications

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“…The MS analysis in EV proteomic studies is usually performed by data-dependent acquisition (DDA) [ 131 ] or data-independent acquisition (DIA) such as SWATH (sequential window acquisition of all theoretical fragment ion) [ 81 ], MS E [ 92 ], and multiplexed MS/MS.…”

Section: Proteomic Methodsmentioning

confidence: 99%

Proteomics of Extracellular Vesicles: Update on Their Composition, Biological Roles and Potential Use as Diagnostic Tools in Atherosclerotic Cardiovascular Diseases

et al. 2020

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Extracellular vesicles (EVs) are lipid-bound vesicles released from cells under physiological and pathological conditions. Basing on biogenesis, dimension, content and route of secretion, they can be classified into exosomes, microvesicles (MVs) and apoptotic bodies. EVs have a key role as bioactive mediators in intercellular communication, but they are also involved in other physiological processes like immune response, blood coagulation, and tissue repair. The interest in studying EVs has increased over the years due to their involvement in several diseases, such as cardiovascular diseases (CVDs), and their potential role as biomarkers in diagnosis, therapy, and in drug delivery system development. Nowadays, the improvement of mass spectrometry (MS)-based techniques allows the characterization of the EV protein composition to deeply understand their role in several diseases. In this review, a critical overview is provided on the EV’s origin and physical properties, as well as their emerging functional role in both physiological and disease conditions, focusing attention on the role of exosomes in CVDs. The most important cardiac exosome proteomic studies will be discussed giving a qualitative and quantitative characterization of the exosomal proteins that could be used in future as new potential diagnostic markers or targets for specific therapies.

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Section: Proteomic Methodsmentioning

confidence: 99%

Proteomics of Extracellular Vesicles: Update on Their Composition, Biological Roles and Potential Use as Diagnostic Tools in Atherosclerotic Cardiovascular Diseases

et al. 2020

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“…Compared to KTR with stable allograft function, KTR with acute T cell-mediated rejection (TCMR) showed significantly decreased PODXL in uEV [ 26 ]. In KTR with chronic antibody-mediated rejection (CAMR) and severely declined kidney function (mean SCr 3.6 mg/dL), PODXL was also one of the most decreased proteins in uEV [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the complement components may provide more specific information. In uEV, complement components 3 (C3), C4-a, C4-b were significantly increased in KTR with CAMR, compared with recipients with long-term graft survival [ 28 ]. C3 also showed the second highest correlation with TCMR among 63 overexpressed proteins in the uEV from KTR [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Urinary Extracellular Vesicles Are a Novel Tool to Monitor Allograft Function in Kidney Transplantation: A Systematic Review

Boer

Woud

et al. 2021

IJMS

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Extracellular vesicles (EVs) are nanoparticles that transmit molecules from releasing cells to target cells. Recent studies link urinary EVs (uEV) to diverse processes such as infection and rejection after kidney transplantation. This, and the unmet need for biomarkers diagnosing kidney transplant dysfunction, has led to the current high level of interest in uEV. uEV provide non-intrusive access to local protein, DNA, and RNA analytics without invasive biopsy. To determine the added value of uEV measurements for detecting allograft dysfunction after kidney transplantation, we systematically included all related literature containing directly relevant information, with the addition of indirect evidence regarding urine or kidney injury without transplantation. According to their varying characteristics, uEV markers after transplantation could be categorized into kidney-specific, donor-specific, and immune response-related (IR-) markers. A few convincing studies have shown that kidney-specific markers (PODXL, ion cotransporters, SYT17, NGAL, and CD133) and IR-markers (CD3, multi-mRNA signatures, and viral miRNA) could diagnose rejection, BK virus-associated nephropathy, and calcineurin inhibitor nephrotoxicity after kidney transplantation. In addition, some indirect proof regarding donor-specific markers (donor-derived cell-free DNA) in urine has been demonstrated. Together, this literature review provides directions for exploring novel uEV markers’ profiling complications after kidney transplantation.

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“…Srivastava et al (64,65) identified that the up-expression of urine ANXA11, Integrin a3, Integrin b3 and TNF-a, and the downregulation of serum PARP1 could be used as candidate proteomic biomarkers for kidney allograft rejection. Furthermore, several proteins, some chemokines and cytokines in blood and urine are also identified as biomarkers for diagnosing CKTR and predicting graft outcomes (66)(67)(68)(69)(70)(71). Several recent efforts have established urinary C-X-C motif chemokine 9 (CXCL9) and CXCL10 as reliable biomarkers for subclinical allograft rejection and for guiding the post-transplant management (66,67).…”

Section: Proteomic Biomarkersmentioning

confidence: 99%

Tackling Chronic Kidney Transplant Rejection: Challenges and Promises

et al. 2021

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Despite advances in post-transplant management, the long-term survival rate of kidney grafts and patients has not improved as approximately forty percent of transplants fails within ten years after transplantation. Both immunologic and non-immunologic factors contribute to late allograft loss. Chronic kidney transplant rejection (CKTR) is often clinically silent yet progressive allogeneic immune process that leads to cumulative graft injury, deterioration of graft function. Chronic active T cell mediated rejection (TCMR) and chronic active antibody-mediated rejection (ABMR) are classified as two principal subtypes of CKTR. While significant improvements have been made towards a better understanding of cellular and molecular mechanisms and diagnostic classifications of CKTR, lack of early detection, differential diagnosis and effective therapies continue to pose major challenges for long-term management. Recent development of high throughput cellular and molecular biotechnologies has allowed rapid development of new biomarkers associated with chronic renal injury, which not only provide insight into pathogenesis of chronic rejection but also allow for early detection. In parallel, several novel therapeutic strategies have emerged which may hold great promise for improvement of long-term graft and patient survival. With a brief overview of current understanding of pathogenesis, standard diagnosis and challenges in the context of CKTR, this mini-review aims to provide updates and insights into the latest development of promising novel biomarkers for diagnosis and novel therapeutic interventions to prevent and treat CKTR.

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Potential urinary extracellular vesicle protein biomarkers of chronic active antibody-mediated rejection in kidney transplant recipients

Cited by 35 publications

References 31 publications

Proteomics of Extracellular Vesicles: Update on Their Composition, Biological Roles and Potential Use as Diagnostic Tools in Atherosclerotic Cardiovascular Diseases

Proteomics of Extracellular Vesicles: Update on Their Composition, Biological Roles and Potential Use as Diagnostic Tools in Atherosclerotic Cardiovascular Diseases

Urinary Extracellular Vesicles Are a Novel Tool to Monitor Allograft Function in Kidney Transplantation: A Systematic Review

Tackling Chronic Kidney Transplant Rejection: Challenges and Promises

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