Prophylaxis Versus Preemptive Anti-cytomegalovirus Approach for Prevention of Allograft Vasculopathy in Heart Transplant Recipients

Potena, Luciano; Grigioni, Francesco; Magnani, Gaia; Lazzarotto, Tiziana; Musuraca, Anna Chiara; Ortolani, Paolo; Coccolo, Fabio; Fallani, Francesco; Russo, Antonio; Branzi, Angelo

doi:10.1016/j.healun.2009.02.009

Cited by 79 publications

(53 citation statements)

References 35 publications

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“…CMV infection is believed to play a key role in CAV progression, possibly through its complex interaction with the host immune system and immunomodulatory effects [20,22]. In our study CMV seropositivity was not associated with CAV and did not correlate with an increase of Ab status.…”

Section: Discussioncontrasting

confidence: 47%

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Occurrence of HLA- and Non-HLA Antibodies after Heart Transplantation are Associated with Cardiac Allograft Vasculopathy

Barten¹,

Dieterlen²,

Garbade³

et al. 2014

Cardiometry

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AimsCardiac allograft vasculopathy (CAV) accounts for major morbidity and mortality late in the heart transplant (HTx) history. The role of antibodies (Abs) directed against human leukocyte antigens (HLA) and non-HLA antigens in the pathogenesis of CAV are still under investigation. Materials and methodsSera of 116 long-term HTx recipients with CAV (n=46) and without CAV (n=70) were analysed by (1) Luminex for Abs against both HLA classes and major histocompatibility complex class I-related chain A (MICA), and by (2) ELISA for Abs against angiotensin-type-1-receptor (AT1R) or endothelin-receptor-A (ETAR). Cellular rejection by endomyocardial biopsies and immunosuppressive drug therapy were analysed, too. ResultsHTx recipients developed higher levels of non-HLA-Abs than of Abs against HLA. CAV appeared more frequently in recipients with non-HLA-Abs (38.3% AT1R; 44.1% ETAR; 13.0% MICA) than in recipients with HLA-Abs (8.7% HLA class I; 8.7% HLA class II). Recipients with non-HLA-Abs developed CAV earlier (73.7±47.4months) than recipients without Abs (85.5±50.6months). ConclusionOccurrence of HLA-Abs and non-HLA-Abs contribute to CAV after HTx. Non-HLA-Abs were connected to an earlier and higher incidence of CAV. Recipients with subclinical cellular rejections and AT1R-Abs and ETAR-Abs as well as recipients with certain donor specific-Abs again HLA and MICA specifities are at risk to develop CAV.

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Section: Discussioncontrasting

confidence: 47%

“…Despite immunological events, there are a number of non-immunological factors that have been implicated in the pathogenesis of CAV such as donor factors, viral infection, immunosuppressive drugs and metabolic risk factors [20]. Among these factors donor's age was identified as risk factor for CAV.…”

Section: Discussionmentioning

confidence: 99%

Occurrence of HLA- and Non-HLA Antibodies after Heart Transplantation are Associated with Cardiac Allograft Vasculopathy

Barten¹,

Dieterlen²,

Garbade³

et al. 2014

Cardiometry

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“…CMV infection (seropositivity) is an independent predictor of progression of transplant vasculopathy independent of cardiovascular risk factors, inflammatory markers and platelet activation (113). This risk is similarly ameliorated by intensive antiviral prophylaxis that reduced intimal thickening compared with patients receiving preemptive anti-CMV therapy for viremia (114). In cardiac recipients studied with vascular ultrasound, prolonging prophylaxis (3 vs. 1 mo) slowed vascular disease over the first year after transplantation (115).…”

Section: Nonimmune Pathways In Cmv-associated Allograft Injurymentioning

confidence: 99%

The Cell Biology of Cytomegalovirus: Implications for Transplantation

Kaminski

Fishman

2016

American Journal of Transplantation

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Interpretation of clinical data regarding the impact of cytomegalovirus (CMV) infection on allograft function is complicated by the diversity of viral strains and substantial variability of cellular receptors and viral gene expression in different tissues. Variation also exists in nonspecific (monocytes and dendritic cells) and specific (NK cells, antibodies) responses that augment T cell antiviral activities. Innate immune signaling pathways and expanded pools of memory NK cells and cd T cells also serve to amplify host responses to infection. The clinical impact of specific memory T cell anti-CMV responses that cross-react with graft antigens and alloantigens is uncertain but appears to contribute to graft injury and to the abrogation of allograft tolerance. These responses are modified by diverse immunosuppressive regimens and by underlying host immune deficits. The impact of CMV infection on the transplant recipient reflects cellular changes and corresponding host responses, the convergence of which has been termed the "indirect effects" of CMV infection. Future studies will clarify interactions between CMV infection and allograft injury and will guide interventions that may enhance clinical outcomes in transplantation.

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“…71 Aggressive, universal, compared to preemptive, CMV prophylaxis postheart transplant ameliorates cardiac allograft vasculopathy. 72 Mechanisms by which CMV causes vasculopathy involve complex, not fully understood, and apparently contradictory interactions with the host immune system. Among these are: the activation of the transcription nuclear factor kappa B by CMV entry into host endothelial cells leading to CMV replication in the cell; release of the cytokines by the immune cells following CMV infection leading to upregulation of adhesion molecules and human leukocyte antigen (HLA) II expression on endothelial cells; vessel wall smooth muscle proliferation caused by CMV cytokine homologs; reduced endothelial nitrous oxide synthesis; and inflammatory responses within the graft.…”

Section: Badamimentioning

confidence: 99%

CMV and transfusions, an old story that's not quite over yet

Badami¹

2014

IJCTM

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Prophylaxis Versus Preemptive Anti-cytomegalovirus Approach for Prevention of Allograft Vasculopathy in Heart Transplant Recipients

Cited by 79 publications

References 35 publications

Occurrence of HLA- and Non-HLA Antibodies after Heart Transplantation are Associated with Cardiac Allograft Vasculopathy

Occurrence of HLA- and Non-HLA Antibodies after Heart Transplantation are Associated with Cardiac Allograft Vasculopathy

The Cell Biology of Cytomegalovirus: Implications for Transplantation

CMV and transfusions, an old story that's not quite over yet

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Prophylaxis Versus Preemptive Anti-cytomegalovirus Approach for Prevention of Allograft Vasculopathy in Heart Transplant Recipients

Cited by 79 publications

References 35 publications

Occurrence of HLA- and Non-HLA Antibodies after Heart Transplantation are Associated with Cardiac Allograft Vasculopathy

Occurrence of HLA- and Non-HLA Antibodies after Heart Transplantation are Associated with Cardiac Allograft Vasculopathy

The Cell Biology of Cytomegalovirus: Implications for Transplantation

CMV and transfusions, an old story that&#39;s not quite over yet

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Product

Resources

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CMV and transfusions, an old story that's not quite over yet