Evaluation of T-Cell Receptor Repertoires in Patients with Long-Term Renal Allograft Survival

Álvarez, Cristiam M.; Opelz, Gerhard; Giraldo, Mabel; Pelzl, Steffen; Renner, Fritz; Weimer, Rolf; Schmidt, Jan; Arbelaez, Mario; García, Luis F.; Süsal, Caner

doi:10.1111/j.1600-6143.2005.00756.x

Cited by 22 publications

(18 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We reported previously that LTS patients with and without immunosuppression show alterations in their T-cell repertoire, suggests predominant expression of particular T-cell subpopulations, and possess increased numbers of circulating T cells with the CD4 ϩ CD25 high phenotype (15,16). These findings indicated that regulatory mechanisms are active in these recipients, and that these phenomena might serve as an explanation for the establishment and maintenance of long-term allograft acceptance in these patients.…”

mentioning

confidence: 73%

Expression of Regulatory T–Cell-Related Molecule Genes and Clinical Outcome in Kidney Transplant Recipients

Álvarez¹,

Opelz²,

García³

et al. 2009

Transplantation

Self Cite

View full text Add to dashboard Cite

Our results suggest that high expression of FOXP3 and chemokine receptor genes in LTS patients are possible indicators of a regulatory process that contributes to long-term allograft acceptance. Markers that were increased in LTS patients were found to be decreased in ChrRx patients, suggesting that rejection may partly be the result of a lack of this regulatory process. FOXP3 and CCR7 and CXCR4 transcripts might be used as markers to distinguish patients who developed long-term allograft acceptance from patients who are prone to ChrRx.

show abstract

mentioning

confidence: 73%

Expression of Regulatory T–Cell-Related Molecule Genes and Clinical Outcome in Kidney Transplant Recipients

Álvarez¹,

Opelz²,

García³

et al. 2009

Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Phenotyping revealed also an increase of CD8 ϩ CD28 Ϫ cells with higher expression of perforin and granzyme A in CR patients compared with TOL patients and healthy individuals (10). The combination of multiple immune-monitoring parameters such as the tolerance expression footprint identified in this study, T cell receptor repertoire alteration (9,47), changes in mononuclear cell phenotype (6,10,46), or ex vivo inhibition of allospecific responses could increase the accuracy of identifying and predicting the tolerant phenotype.…”

Section: Discussionmentioning

confidence: 99%

Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance

Brouard

Mansfield

Braud

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

336

312

View full text Add to dashboard Cite

Long-term allograft survival generally requires lifelong immunosuppression (IS). Rarely, recipients display spontaneous ''operational tolerance'' with stable graft function in the absence of IS. The lack of biological markers of this phenomenon precludes identification of potentially tolerant patients in which IS could be tapered and hinders the development of new tolerance-inducing strategies. The objective of this study was to identify minimally invasive blood biomarkers for operational tolerance and use these biomarkers to determine the frequency of this state in immunosuppressed patients with stable graft function. Blood gene expression profiles from 75 renal-transplant patient cohorts (operational tolerance/acute and chronic rejection/stable graft function on IS) and 16 healthy individuals were analyzed. A subset of samples was used for microarray analysis where three-class comparison of the different groups of patients identified a ''tolerant footprint'' of 49 genes. These biomarkers were applied for prediction of operational tolerance by microarray and real-time PCR in independent test groups. Thirty-three of 49 genes correctly segregated tolerance and chronic rejection phenotypes with 99% and 86% specificity. The signature is shared with 1 of 12 and 5 of 10 stable patients on triple IS and low-dose steroid monotherapy, respectively. The gene signature suggests a pattern of reduced costimulatory signaling, immune quiescence, apoptosis, and memory T cell responses. This study identifies in the blood of kidney recipients a set of genes associated with operational tolerance that may have utility as a minimally invasive monitoring tool for guiding IS titration. Further validation of this tool for safe IS minimization in prospective clinical trials is warranted.kidney transplantation ͉ microarray ͉ tolerant ͉ genomics ͉ immunosuppression titration D espite continuous improvement in renal allograft survival over the last decade, the half-life of renal allografts has increased marginally because of accrual of chronic graft nephropathy from drug-related nephrotoxicity and chronic rejection (1, 2). Patients facing life-long immunosuppression (IS) have increased risk of infection and malignancy (3), whereas insufficient immunosuppressive drug exposure or interruption usually increases rejection risk (4). However, spontaneous and long-term graft acceptance is observed in a small number of patients after solid-organ transplantation (5, 6), years after total withdrawal of immunosuppressive drugs, confirming that a clinical operational state of tolerance to a mismatched graft, described as ''a state of quiescence of the transplanted organ, functioning without a destructive immune response'' (7), can indeed occur and exist in humans. However, the frequency of this observation in the kidney transplant population is unknown and, currently, we cannot identify patients primed to develop this immune adaptation or monitor for the stability of this status of ''operational tolerance.'' The operationally tolerant kidney transpla...

show abstract

“…However, a direct role of T R cells in preventing CR is still unclear. Proportional increases of circulating T R cells (CD4 ϩ CD25 hi and FoxP3 ϩ ) from patients with long-term allograft survival was reported (31,32), whereas patient with CR showed a decreased level of T R cells and FoxP3 transcripts (33). An increased ratio of low avidity CD8 T R cells over high avidity T effectors is another example of various types of T R cells controlling CR development (34).…”

Section: Adaptive Immunitymentioning

confidence: 95%

Overcoming Chronic Rejection—Can it B?

Kwun

Knechtle

2009

Transplantation

View full text Add to dashboard Cite

Despite the success of immunosuppressive drug therapy to reduce the incidence of acute rejection in organ transplantation, chronic rejection is still an impediment to long-term graft survival and tolerance. There is a growing body of evidence that B-cell production of alloantibody is an important element in the genesis of chronic rejection. Effector function of B cells in transplantation is not specifically targeted by current T-cell-directed therapeutic approaches. We briefly discuss the origin, animal models, diagnostic methods, and currently available B cell reagents that might be used in combination with existing immunosuppressive regimens to address B-cell-mediated allograft injury.

show abstract

Evaluation of T-Cell Receptor Repertoires in Patients with Long-Term Renal Allograft Survival

Cited by 22 publications

References 29 publications

Expression of Regulatory T–Cell-Related Molecule Genes and Clinical Outcome in Kidney Transplant Recipients

Expression of Regulatory T–Cell-Related Molecule Genes and Clinical Outcome in Kidney Transplant Recipients

Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance

Overcoming Chronic Rejection—Can it B?

Contact Info

Product

Resources

About