scholarly journals Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Estefanía Tarazón ◽  
Carolina Gil-Cayuela ◽  
María García Manzanares ◽  
Marta Roca ◽  
Francisca Lago ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Transplant ◽  
Allograft Rejection ◽  
Transplant Rejection ◽  
Cardiac Allograft ◽  
Cardiac Allograft Rejection ◽  
Non Invasive ◽  
Novel Approach ◽  
Sphingosine 1 Phosphate ◽  
Cardiac Rejection

Abstract Accumulating evidence has confirmed that the expression of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is downregulated in heart failure and cardiac allograft rejection. Although many SERCA2a-related genes and proteins involved in the regulation of myocardial Ca2+ fluxes have been explored, its related metabolites remain poorly studied. Our main objective was to identify circulating SERCA2a-related metabolites altered in cardiac allograft rejection and to determine whether these could serve as non-invasive biomarkers. Sixty plasma samples from adult heart transplant were included in a metabolomic analysis. Sphingosine-1 phosphate (S1P), metabolite closely related with SERCA, were increased in patients with cardiac rejection (p < 0.0001). S1P discriminated between patients with and without rejection: normal grafts vs. all rejecting grafts (AUC = 0.911, p < 0.0001), normal grafts vs. Grade 1 R (AUC = 0.819, p < 0.01), Grade 2 R (AUC = 0.911, p < 0.0001), Grade 3 R (AUC = 0.996, p < 0.0001). In addition, we found changes in key enzymes and receptors of S1P pathway analysed on explanted hearts from heart failure patients. This preliminary study reveals that circulating S1P determination could be a novel approach to detect cardiac rejection, showing a robust capability for detection that improves gradually with the severity of rejection. These alterations could be relevant to better understand the involvement of calcium regulation on the pathophysiology of rejection.

scholarly journals A Changing Paradigm in Heart Transplantation: An Integrative Approach for Invasive and Non-Invasive Allograft Rejection Monitoring

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 201
Author(s):  
Alessia Giarraputo ◽  
Ilaria Barison ◽  
Marny Fedrigo ◽  
Jacopo Burrello ◽  
Chiara Castellani ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Heart Transplant ◽  
Allograft Rejection ◽  
Exclusion Process ◽  
Cardiac Allograft ◽  
Molecular Techniques ◽  
Integrative Approach ◽  
Comprehensive Overview ◽  
Cardiac Allograft Rejection ◽  
Non Invasive

Cardiac allograft rejection following heart transplantation is challenging to diagnose. Tissue biopsies are the gold standard in monitoring the different types of rejection. The last decade has seen an increased emphasis on identifying non-invasive methods to improve rejection diagnosis and overcome tissue biopsy invasiveness. Liquid biopsy, as an efficient non-invasive diagnostic and prognostic oncological monitoring tool, seems to be applicable in heart transplant follow-ups. Moreover, molecular techniques applied on blood can be translated to tissue samples to provide novel perspectives on tissue and reveal new diagnostic and prognostic biomarkers. This review aims to provide a comprehensive overview of the state-of-the-art of the new methodologies in cardiac allograft rejection monitoring and investigate the future perspectives on invasive and non-invasive rejection biomarkers identification. We reviewed literature from the most used scientific databases, such as PubMed, Google Scholar, and Scopus. We extracted 192 papers and, after a selection and exclusion process, we included in the review 81 papers. The described limitations notwithstanding, this review show how molecular biology techniques and omics science could be deployed complementarily to the histopathological rejection diagnosis on tissue biopsies, thus representing an integrated approach for heart transplant patients monitoring.

Diastolic strain imaging: a new non-invasive tool to detect subclinical myocardial dysfunction in early cardiac allograft rejection

2019 ◽  
Vol 36 (2) ◽  
pp. 317-323
Author(s):  
Robert Chamberlain ◽  
Gregory M. Scalia ◽  
Kenji Shiino ◽  
David G. Platts ◽  
Surendran Sabapathy ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Myocardial Dysfunction ◽  
Strain Imaging ◽  
Cardiac Allograft ◽  
Cardiac Allograft Rejection ◽  
Non Invasive

P761The effect of extracorporeal photopheresis on cardiac allograft rejection and on lymphocyte subclasses

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Teszak ◽  
A Assabiny ◽  
A Kiraly ◽  
Z Tarjanyi ◽  
N Parazs ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Lymphocytes ◽  
Heart Transplant ◽  
Allograft Rejection ◽  
Cytotoxic T Cells ◽  
Cardiac Allograft ◽  
Extracorporeal Photopheresis ◽  
Cardiac Allograft Rejection ◽  
Cellular Rejection

Abstract Background Cardiac allograft rejection is known to have a profound impact on graft survival and mortality after heart transplant. Previous data on the efficacy of extracorporeal photopheresis (ECP) in the management of cardiac allograft rejection is encouraging. Though, clear evidence on the exact indication and data regarding its effect on distinct lymphocyte subtypes are still lacking. Based on their cytokine production, both helper and cytotoxic T cells can differentiate into either regulatory cells participating in the suppression of rejection or into effector cells responsible for its maintenance. Regulatory T cells are essential for the termination of rejection, while B lymphocytes and natural killer (NK) cells contribute to it. Purpose We aimed to investigate the anti-rejection efficacy and the impact of ECP on peripheral blood lymphocyte subclasses in adult heart transplant recipients. Methods In a retrospective analysis of 12 consecutive patients treated with ECP for cardiac allograft rejection between 2013 and 2019, we examined the grade of rejection in endomyocardial biopsies (EMB) based on the International Society for Heart and Lung Transplantation classification. We analysed the absolute counts and the percentages of helper, cytotoxic and regulatory T cells, B lymphocytes and NK cells with fluorescence activated cell sorting. Measurements were performed both before and after the ECP treatment period. Data values were given as either mean±standard deviation or median [min–max]. Results The patients underwent 26 [2–39] ECP treatments in addition to standard immunosuppressant therapy. Whereas grade 2R cellular rejection was detected in 83% of the cases prior to initiating ECP, none of the examined EMB specimen revealed rejection greater than grade 1R cellular rejection post ECP therapy. The average grade of cellular rejection improved significantly (1.25±0.45 vs. 0.50±0.53; p=0.022). The absolute count and the percentage of helper T cells increased significantly post ECP therapy (0.34 G/l±0.26 G/l vs. 0.51 G/l±0.39 G/l; p=0.018 and 3.43%±2.24% vs. 5.98%±3.64%; p=0.017, respectively). There was also a significant rise in the percentage of cytotoxic T cells (2.33%±1.46% vs. 4.16±2.98%; p=0.027). We noticed an almost significant twofold increase in the percentage of regulatory T cells on completion of the ECP therapy (0.20%±0.22% vs. 0.37%±0.20%; p=0.060). Neither B lymphocyte nor NK cell counts revealed any significant changes. Conclusion ECP was effective in reducing the severity of cardiac allograft rejection episodes. The significant decrease in rejection rates might be indicative of the predominance of anti-inflammatory helper and cytotoxic T cell subpopulations and the increase of regulatory T cell count post ECP therapy. However, discussion of the results are limited by small sample size and the effect of medical therapy on the lymphocytes.

Troponin T as a non-invasive marker of cardiac allograft rejection

The Lancet ◽  
1993 ◽  
Vol 341 (8848) ◽  
pp. 838 ◽  
Author(s):  
Mojgan Hossein-Nia ◽  
Jorge Mascaro ◽  
WilliamJ. Mckenna ◽  
AndrewJ. Murday ◽  
DavidW. Holt
Keyword(s):  
Allograft Rejection ◽  
Troponin T ◽  
Cardiac Allograft ◽  
Cardiac Allograft Rejection ◽  
Non Invasive

scholarly journals The mechanism of heart failure caused by cardiac allograft rejection

1991 ◽  
Vol 101 (3) ◽  
pp. 446-449 ◽  
Author(s):  
Verdi J. DiSesa ◽  
Paolo Masetti ◽  
Maurizio Diaco ◽  
Frederick J. Schoen ◽  
James D. Marsh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Allograft Rejection ◽  
Cardiac Allograft ◽  
Cardiac Allograft Rejection

Recognition of Acute Cardiac Allograft Rejection From Serial Integrated Backscatter Analyses in Human Orthotopic Heart Transplant Recipients

Circulation ◽  
1997 ◽  
Vol 95 (1) ◽  
pp. 140-150 ◽  
Author(s):  
Christiane E. Angermann ◽  
Kirsten Nassau ◽  
Hans-Ulrich Stempfle ◽  
Thomas M. Kru¨ger ◽  
Ralph Drewello ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Allograft Rejection ◽  
Cardiac Allograft ◽  
Transplant Recipients ◽  
Orthotopic Heart Transplant ◽  
Integrated Backscatter ◽  
Cardiac Allograft Rejection ◽  
Heart Transplant Recipients

scholarly journals White Blood Cell Differentials Enrich Whole Blood Expression Data in the Context of Acute Cardiac Allograft Rejection

2012 ◽  
Vol 6 ◽  
pp. BBI.S9197 ◽  
Author(s):  
Casey P. Shannon ◽  
Zsuzsanna Hollander ◽  
Janet Wilson-Mcmanus ◽  
Robert Balshaw ◽  
Raymond T. Ng ◽  
...  
Keyword(s):  
Whole Blood ◽  
Allograft Rejection ◽  
Cardiac Allograft ◽  
Expression Data ◽  
Molecular Processes ◽  
Cardiac Allograft Rejection ◽  
Non Invasive ◽  
False Discovery ◽  
Biological Interpretation ◽  
Promising Avenue

Acute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) ≤ 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.

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