Benefit of immune monitoring in heart transplant patients using ATP production in activated lymphocytes

Kobashigawa, Jon A.; Kiyosaki, K.; Patel, Jignesh; Kittleson, M.; Kubak, B.; Davis, Stephanie N.; Kawano, M.; Ardehali, A.

doi:10.1016/j.healun.2009.12.015

Cited by 88 publications

(80 citation statements)

References 9 publications

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“…Although a statistically determined target range is recommended, it can be assumed that strong, inter-individual variations may occur in the immune response, which is why it is also recommended that individual patients be monitored individually over time, but this is very timeconsuming and expensive. Similar results to kidney transplantation have also been obtained in the field of heart transplantation [10,11] .…”

Section: Biomarkers Of Immune Activation Atp Concentration In Cd4 T-csupporting

confidence: 79%

Biomarkers in blood for individualization of the pharmacotherapy with immunosuppressive drugs after transplantation of solid organs

Wieland

Shipkova

2015

LaboratoriumsMedizin

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Abstract:The success of transplantation medicine is closely associated with the introduction of potent immunosuppressive drugs. Therapy guidance of the calcineurin inhibitors cyclosporine and tacrolimus as well as the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus is achieved by therapeutic drug monitoring (TDM). For other immunosuppressive drugs such as mycophenolic acid, TDM is not established. It has been suggested that a better individualization of pharmacotherapy could be helpful in avoiding over-and underimmunosuppression, which have been associated with poor long-term outcome of grafts and patients. Therefore, a search for biomarkers that could complement TDM, thereby allowing a better individualization of therapy, is ongoing worldwide. Pharmacodynamic biomarkers in transplantation medicine can be either non-drug-specific, aiming at assessing the global effect on the immune system, or drug-specific, aiming at recording the pharmacologic effect on a drug target. Non-specific pharmacodynamic biomarkers can reflect the degree of immune activation by measuring T-or B-cell activation, the development of operational tolerance by monitoring, e.g., regulatory T-cells, or the graft damage by measuring cell-free DNA released by the graft in response to injury. Drug-specific pharmacodynamic biomarkers have been published for mycophenolic acid, calcineurin, and mTOR inhibitors. The field of biomarker research to complement TDM for a better individualization of immunosuppression is still in its infancy, and controlled prospective clinical trials are needed to unravel or dismiss the potential of particular biomarkers or biomarker combinations in various patient cohorts with different grafts.

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Section: Biomarkers Of Immune Activation Atp Concentration In Cd4 T-csupporting

confidence: 79%

Biomarkers in blood for individualization of the pharmacotherapy with immunosuppressive drugs after transplantation of solid organs

Wieland

Shipkova

2015

LaboratoriumsMedizin

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“…In a further study [44] with 296 adult heart transplant recipients, the average iATP values were significantly lower during infection than compared to stable patients. The average iATP concentrations, however, were not significantly different during rejection when compared to stable patients.…”

Section: Atp Concentration In Cd4 D T Lymphocytesmentioning

confidence: 81%

“…Further studies have been published on the use of the ImmuKnow Cylex test in heart transplant patients with infection and rejection [43,44]. It was demonstrated that patients with infection had significantly lower iATP values and patients with rejection significantly higher iATP values compared to stable heart transplant recipients [43].…”

Section: Atp Concentration In Cd4 D T Lymphocytesmentioning

confidence: 99%

Biomarkers

Oellerich

Brandhorst

Shipkova

et al. 2012

Therapeutic Drug Monitoring

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“…They showed that values measured to be less than 200 ng ATP/ml may predict high risk for infection within 30 days ( Figure 2). 26 The data were underpowered to define an upper cutoff for risk of rejection but suggest that a pharmacodynamic assay for immunosuppression is possible and will advance efforts to allow individualization of immunosuppression. These data are consistent with studies examining this test in kidney, pancreas, and liver transplants.…”

Section: Immunosuppression and Tolerancementioning

confidence: 99%