Subclinical Inflammation and Prothrombotic State in Heart Transplant Recipients: Impact of Cyclosporin Microemulsion vs. Tacrolimus

White, Michel; Ross, Heather J.; Haddad, Haissam; Leblanc, Marie-Hélène; Racine, Normand; Pflugfelder, Peter W.; Giannetti, Nadia; Davies, Ross A.; Azevêdo, Eduardo Ribeiro de; Isaac, Debra; Burton, Jeffrey R.; Ferguson, Roger K.; Genest, Jacques

doi:10.1097/01.tp.0000232286.22319.e0

Cited by 22 publications

(15 citation statements)

References 45 publications

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“…This assay has already been used successfully by us to demonstrate that dysregulated genes in OS patients are involved closely with self‐tolerance and autoimmunity. Endothelin 1 (EDN1) and P‐selectin (SELP), which were reported previously to be regulated by CsA therapy [25,26], were found by us to have the highest mRNA expression change after CsA therapy. The high expression of these genes is an acceptable explanation for the renal toxicity induced by CsA [27].…”

Section: Discussionmentioning

confidence: 53%

Selective clinical and immune response of the oligoclonal autoreactive T cells in Omenn patients after cyclosporin A treatment

Lev

Simon

Amariglio

et al. 2012

Clinical and Experimental Immunology

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SummaryThe immunological hallmark of Omenn syndrome (OS) is the expansion and activation of an oligoclonal population of autoreactive T cells. These cells should be controlled rapidly by immunosuppressive agents, such as cyclosporin A (CsA), to avoid tissue infiltration and to improve the general outcome of the patients. Here we studied the clinical and the immune response to CsA in two Omenn patients and also examined the gene expression profile associated with good clinical response to such therapy. T cell receptor diversity was studied in cells obtained from OS patients during CsA therapy. Characterization of gene expression in these cells was carried out by using the TaqMan low-density array. One patient showed complete resolution of his symptoms after CsA therapy. The other patient showed selective response of his oligoclonal T cell population and combination therapy was required to control his symptoms. Transcriptional profile associated with good clinical response to CsA therapy revealed significant changes in 26·6% of the tested genes when compared with the transcriptional profile of the cells before treatment. Different clinical response to CsA in two OS patients is correlated with their immunological response. Varying clonal expansions in OS patients can cause autoimmune features and can respond differently to immunosuppressive therapy; therefore, additional treatment is sometimes indicated. CsA for OS patients causes regulation of genes that are involved closely with self-tolerance and autoimmunity.

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Section: Discussionmentioning

confidence: 53%

Selective clinical and immune response of the oligoclonal autoreactive T cells in Omenn patients after cyclosporin A treatment

Lev

Simon

Amariglio

et al. 2012

Clinical and Experimental Immunology

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“…Early studies in renal transplant patients suggest an increased incidence of thrombosis with cyclosporine 58,61 and this is corroborated in cardiac transplant patients. 62 Subsequent prospective studies show no increase in thromboembolic events with cyclosporine therapy. 63,64 With this mixed literature, and many comorbid factors in transplant patients that increase thrombotic risk (steroid use, inflammation, surgery), it is difficult to conclude whether or not cyclosporine is prothrombotic in IBD patients.…”

Section: Cyclosporine and Tacrolimusmentioning

confidence: 98%

Thrombosis and inflammatory bowel disease: A call for improved awareness and prevention

Zitomersky

Verhave

Trenor

2011

Inflammatory Bowel Diseases

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Thrombotic complications in patients with inflammatory bowel disease (IBD) are common and require improved awareness and prevention. In this review the interface between IBD and thrombosis is discussed, with emphasis on risk assessment and data to aid clinical decision making. Thromboembolic complications are 3-fold more likely in IBD patients than controls and the relative risk exceeds 15 during disease flares. Improved assessment of thrombosis risk for an individual patient includes thorough personal and family history and awareness of prothrombotic medications and lifestyle choices. Patients with the highest risk of thrombosis are those with active colonic disease, personal or strong family history of thrombosis, and those with significant acquired risk factors. Combined risk factors or hospitalization should prompt mechanical thromboprophylaxis. Indications for prophylactic anticoagulation are not defined currently by clinical studies, especially in pediatric patients, although some groups now advocate prophylactic anticoagulation for all hospitalized IBD patients and even some outpatients with disease flares. Thrombosis management requires a multidisciplinary therapeutic approach to balance anticoagulation and bleeding risk. While bleeding may occur with anticoagulation in IBD, data and experience indicate that therapeutic heparin is safe and bleeding manifestations can be managed supportively in most patients. Until prospective trials of prophylactic anticoagulation are published, management of thrombotic risk and prophylaxis in IBD will remain a clinical challenge.

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“…Immunologic and transplant related mechanisms include donor age, HLA mismatches, rejections, and selected infections such as cytomegalovirus. Non-immune mechanisms implicated in the development of CAV include traditional risk factors such as hypertension, dyslipidemia, metabolic syndrome, diabetes, obesity, and smoking [3] .…”

Section: The Pathogenesis Of Cav: An Inflammatory Perspectivementioning

confidence: 99%

“…T cells activation also stimulates the expression of adhesion molecules (intercellular cell adhesion molecule -1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin thereby activating endothelial cells, enabling recruitment of neutrophils and the development of CAV [11,[17][18][19][20][21][22][23] . Indeed most pro-inflammatory markers are elevated early and late following CTx [3,24] . Taken together, these data strongly suggest that transplantation is a significant pro-inflammatory condition.…”

Section: The Pathogenesis Of Cav: An Inflammatory Perspectivementioning

confidence: 99%

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Effects of Immunosuppressive agents on neutrophils inflammatory response in humans: An inflammatory perspective on coronary allograft vasculopathy

White

2016

Inflamm Cell Signal

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Cardiac transplantation (CTx) has improved survival in patients with advanced heart failure. Unfortunately, the conditional survival remains less than 15 years. The primary cause of mortality at 5 years following a CTx is the development of accelerated coronary atherosclerosis named coronary allograft vasculopathy (CAV). The neutrophils likely play an important role in this diffuse inflammatory process. Nevertheless, the contribution of the neutrophils on the pathogenesis of CAV is poorly understood. Regardless of their essential contribution for the prevention of graft rejection, immunosuppressive drugs (IDs) may have detrimental effects via some pro-inflammatory activities. This review presents the role of neutrophils on vascular inflammation and on the biologic effects of diverse immunosuppressive agents including mTOR inhibitors in the context of the pathophysiology of CAV. We investigated the impact of different IDs on the inflammatory responses of isolated human neutrophils harvested from healthy controls and herein, we reported on some novel characteristics of everolimus (EVE) on isolated neutrophils in comparison with other immunosuppressive agents. These biologic effects may contribute to their beneficial effects on the allograft vasculature and consequently on the prevention of CAV.

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Subclinical Inflammation and Prothrombotic State in Heart Transplant Recipients: Impact of Cyclosporin Microemulsion vs. Tacrolimus

Cited by 22 publications

References 45 publications

Selective clinical and immune response of the oligoclonal autoreactive T cells in Omenn patients after cyclosporin A treatment

Selective clinical and immune response of the oligoclonal autoreactive T cells in Omenn patients after cyclosporin A treatment

Thrombosis and inflammatory bowel disease: A call for improved awareness and prevention

Effects of Immunosuppressive agents on neutrophils inflammatory response in humans: An inflammatory perspective on coronary allograft vasculopathy

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