Noninvasive Tim-3 Messenger RNA Evaluation in Renal Transplant Recipients With Graft Dysfunction

Manfro, Roberto Ceratti; Aquino-Dias, E.C.; Joelsons, Gabriel; Nogare, Aline L.; Carpio, Virna Nowotny; Gonçalves, Luiz Felipe Santos

doi:10.1097/tp.0b013e3181914246

Cited by 32 publications

(18 citation statements)

References 30 publications

(19 reference statements)

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“…Furthermore, patients with acute rejection show much higher urine TIM-3 mRNA levels than those with other causes of allograft dysfunction or non-rejecting controls(51, 52). While larger studies will be needed to confirm these findings, these data suggest potential utility of TIM-3 mRNA measurement as a non-invasive tool in the diagnosis of allograft dysfunction.…”

Section: Tim Molecules As Markers Of Allograft Injurymentioning

confidence: 96%

The Emerging Role of the TIM Molecules in Transplantation

Yeung

McGrath

Najafian

2011

American Journal of Transplantation

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Since their discovery in 2001, the T cell immunoglobulin mucin (TIM) family members have been shown to play important roles in the regulation of immune responses. The TIM family comprises of eight genes in the mouse, three of which are conserved in humans (TIM-1, TIM-3 and TIM-4). Initially, TIM-1 and TIM-3 were thought to be expressed solely on T cells. However, emerging data suggest a much broader expression pattern where their presence on APCs confers differing functions, including the ability to mediate phagocytosis. In contrast, TIM-4 is exclusively expressed on APCs. Together, the TIM molecules provide a functional repertoire for determining the fate of T cell activation and differentiation. To date, much of the knowledge about the TIM family members has been garnered from models of asthma, allergy and autoimmunity. More recently, data from experimental models of transplantation demonstrate that TIM family members are also key in alloimmunity. This review will serve to highlight the emerging data regarding this unique family of molecules, and to identify their potential in transplantation tolerance.

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Section: Tim Molecules As Markers Of Allograft Injurymentioning

confidence: 96%

The Emerging Role of the TIM Molecules in Transplantation

Yeung

McGrath

Najafian

2011

American Journal of Transplantation

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“…Most research efforts in biomarkers for renal transplant patients so far have focused on the identification of rejection among those with graft dysfunction; a comprehensive but nonexhaustive list of these markers is presented in Table 3 [54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70]. Although several hundred articles have described strong associations between peripheral biomarkers and rejection, few of them have gone beyond primary association analysis to present a formal evaluation of the diagnostic performance of the proposed marker.…”

Section: Biomarkers In Kidney Transplant Patientsmentioning

confidence: 99%

Biomarkers in native and transplant kidneys

Serres

Varghese²,

Levin³

2012

Current Opinion in Nephrology and Hypertension

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“…[96][97][98] Ding et al [96] reported that mRNA levels of CD103, a cell surface molecule involved in the homing of CTLs, were significantly higher in recipients experiencing acute rejection than in patients presenting with other pathologies or stable graft function. In an impressive analysis of 115 patients (160 biopsies), Manfro et al [100] evaluated TIM3 mRNA expression in kidney tissue and peripheral blood, as well as urinary cells. Similar associations were observed for FOXP3 mRNA levels.…”

Section: Gene Expression In Urinary Sedimentmentioning

confidence: 99%

“…Tatapudi et al [97] found increased mRNA levels of interferon-inducible protein 10 (IP-10; also known as CXCL10) [sensitivity 100%, specificity 78%] and chemokine receptor CXCR3 (sensitivity 63%, specificity 83%) in rejecting kidney allograft recipients. [100] The aforementioned studies suggest that urinary cell gene expression profiling has diagnostic potential, especially for detection of acute T-cell-mediated rejection. [98] Remarkably, expression of FOXP3 mRNA was found to predict rejection reversal and failure.…”

Section: Gene Expression In Urinary Sedimentmentioning

confidence: 99%

Detecting Adaptive Immunity

Böhmig

Wahrmann²,

Säemann³

2010

Mol Diag Ther

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In recent decades, continuous improvements in immunosuppressive therapy have led to a significant increase in kidney allograft survival. Despite innovative developments and improvements in immunosuppression, chronic allograft injury and late graft loss still remain major causes of morbidity and mortality. In clinical practice, long-term immunosuppression is adapted and fine-tuned according to drug levels, kidney function, and biopsy results. As an invasive procedure, indication biopsy still represents an indispensible diagnostic gold standard. However, in an effort to further improve outcomes on the basis of individualized treatment, there is an urgent need for noninvasive assays, as well as biomarkers, to more accurately monitor allogeneic responses and predict the risk of acute and chronic allograft rejection. This article discusses strategies for immune monitoring of T-cell responsiveness and humoral alloreactivity. Furthermore, new microarray and gene profiling data are highlighted, which may identify hyporesponsive transplant recipients who could benefit from a reduction or even withdrawal of immunosuppression. Finally, supplementary transplant risk assessment markers, such as soluble CD30 and urinary effector molecule analysis, are discussed as promising new tools. Recent developments and improvements in test principles to monitor and predict allograft immunity are encouraging and may herald the transition of present empiric immunosuppression to individualized immunosuppressive treatment. Nonetheless, before implementation of immune monitoring in routine clinical practice, there is still a need for prospective trials designed to clarify the actual diagnostic potential of individual test systems in a therapeutic context.

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Noninvasive Tim-3 Messenger RNA Evaluation in Renal Transplant Recipients With Graft Dysfunction

Abstract: T-cell immunoglobulin domain, mucin domain mRNA quantification by real-time polymerase chain reaction in PBL and UC of renal transplant patients undergoing DGF or AGD may become a useful tool for an accurate noninvasive diagnosis of AR.

Cited by 32 publications

References 30 publications

The Emerging Role of the TIM Molecules in Transplantation

The Emerging Role of the TIM Molecules in Transplantation

Biomarkers in native and transplant kidneys

Detecting Adaptive Immunity

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