Analysis of Immune Markers in Human Cardiac Allograft Recipients and Association With Coronary Artery Vasculopathy

Poggio, Emilio D.; Roddy, Meagan; Riley, Jocelyn; Clemente, Michael J.; Hricik, Donald E.; Starling, Randall C.; Young, James B.; Gus, Barbara; Yamani, Mohamad H.; Heeger, Peter S.

doi:10.1016/j.healun.2004.12.110

Cited by 24 publications

(9 citation statements)

References 26 publications

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“…82 Given the impact of antidonor cellular immunity, enzymelinked immunospot (ELISPOT)-based antidonor T-cell immunity combined with flow cytometer-based antidonor alloantibody might be useful in detection of CAV. 83 The AlloMap gene-expression test, initially validated for the detection of acute rejection episodes, has recently been evaluated for its association with CAV. 84 In this retrospective analysis, CAV was associated with an increased AlloMap gene-expression score.…”

Section: Biomarkers and Gene Profilingmentioning

confidence: 99%

Cardiac Allograft Vasculopathy

2008

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Abstract-Cardiac allograft vasculopathy (CAV) continues to limit the long-term success of cardiac transplantation.Recent insights have underscored the fact that innate and adaptive immune responses are involved in the pathogenesis of CAV. Vascular lesions are the result of cumulative endothelial injuries induced both by alloimmune responses and by nonspecific insults (including ischemia-reperfusion injury, viral infections, and metabolic disorders) in the context of impaired repair mechanisms. Intravascular ultrasound is the most sensitive method for detection of CAV, and progressive intimal thickening in the first posttransplant year identifies patients at high risk for future cardiovascular events. Encouraging results with regard to the detection of CAV by noninvasive methods should be an incentive to apply routine noninvasive imaging during mid-to long-term follow-up. Improved immunosuppressive drugs, including mycophenolate mofetil and proliferation signal inhibitors, as well as statins (in part via immunomodulation), have beneficial effects on CAV progression, although there is still a need to confirm the impact of vasodilators in improving outcome after heart transplantation. Coronary revascularization for CAV is only palliative, with no long-term survival benefit. Three main strategies for CAV prevention are currently under investigation: inhibition of growth factors and cytokines, cell therapy, and tolerance induction. However, because individual responses to an allograft change over time, assays to monitor the recipient's immune response and individualized methods for therapeutic immune modulation are clearly needed. (Circulation. 2008;117:2131-2141.)

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Section: Biomarkers and Gene Profilingmentioning

confidence: 99%

Cardiac Allograft Vasculopathy

2008

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“…Transplant glomerulopathy is one particular pathological correlate of chronic renal allograft dysfunction; a recent retrospective review of 1320 biopsies [13] demonstrated that 73% of those with transplant glomerulopathy had evidence of alloantibody-mediated injury. There is also long-standing evidence correlating indirect alloreactivity with chronic rejection of kidney, heart, lung and liver transplants [14][15][16][17]. Most recently, Bestard et al [18] undertook tests of direct and indirect alloreactivity in 34 long-standing living-donor renal transplant recipients; indirect alloreactivity was found to be significantly correlated with proteinuria, indicating ongoing graft dysfunction.…”

Section: Indirect Allorecognition and Chronic Rejectionmentioning

confidence: 99%

The importance of the indirect pathway of allorecognition in clinical transplantation

Gökmen

Lombardi

Lechler

2008

Current Opinion in Immunology

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“…Several studies have provided evidence that alloreactive T cells detected in peripheral blood (21–26), the quantity of cell-free, donor DNA in recipient’s plasma (27, 28), serum angiogenesis-related factors (29–33), serum anti-HLA antibodies and autoantibodies (34–39) and several peripheral blood gene profiles are associated with acute or chronic heart graft injury (40–43). Prospective, multicenter, comparative analyses of candidate biomarkers for AR and CAV have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study

Starling

Stehlik

Baran

et al. 2016

American Journal of Transplantation

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Identification of biomarkers that assess post-transplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first post-transplant year. The primary endpoint was a composite of death, graft loss/re-transplantation, biopsy proven acute rejection (BPAR) and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p<0.03) and with recipient anti-HLA antibody (p<0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR p<0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9–218) combined with decreases in endothelin-1: (OR 0.14; 95%CI:0.02–0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation.

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Analysis of Immune Markers in Human Cardiac Allograft Recipients and Association With Coronary Artery Vasculopathy

Cited by 24 publications

References 26 publications

Cardiac Allograft Vasculopathy

Cardiac Allograft Vasculopathy

The importance of the indirect pathway of allorecognition in clinical transplantation

Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study

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