Epigenetics: A New Model for Intracellular Parasite-Host Cell Regulation.

Intracellular protozoan parasites are an extremely important class of pathogens that cause a spectrum of diseases in human and animal hosts. There is a growing body of evidence suggesting that protozoan parasites, like other prokaryotic and viral pathogens, manipulate host cells via epigenetic modifications of the host genome that alter transcription and corresponding signaling pathways. In light of these data, we examine the role of epigenetics in downregulation of host macrophages by Leishmania that could potentially lead to a permanent state of inactivation, thus favoring pathogen survival and disease progression.

Plasma protein biosignatures for detection of cardiac allograft vasculopathy.

BACKGROUND: Coronary angiography remains the most widely used tool for routine screening and diagnosis of cardiac allograft vasculopathy (CAV), a major pathologic process that develops in 50% of cardiac transplant recipients beyond the first year after transplant. Given the invasiveness, expense, discomfort, and risk of complications associated with angiography, a minimally invasive alternative that is sensitive and specific would be highly desirable for monitoring CAV in patients. METHODS: Plasma proteomic analysis using isobaric tags for relative and absolute quantitation-matrix-assisted laser desorption ionization double time-of-flight mass spectrometry was carried out on samples from 40 cardiac transplant patients (10 CAV, 9 non-significant CAV, 21 possible CAV). Presence of CAV was defined as left anterior descending artery diameter stenosis ≥ 40% by digital angiography and quantitatively measured by blinded expert appraisal. Moderated t-test robust-linear models for microarray data were used to identify biomarkers that are significantly differentially expressed between patient samples with CAV and with non-significant CAV. A proteomic panel for diagnosis of CAV was generated using the Elastic Net classification method. RESULTS: We identified an 18-plasma protein biomarker classifier panel that was able to classify and differentiate patients with angiographically significant CAV from those without significant CAV, with an 80% sensitivity and 89% specificity, while providing insight into the possible underlying immune and non-alloimmune contributory mechanisms of CAV. CONCLUSION: Our results support of the potential utility of proteomic biomarker panels as a minimally invasive means to identify patients with significant, angiographically detectable coronary artery stenosis in the cardiac allograft, in the context of post-cardiac transplantation monitoring and screening for CAV. The potential biologic significance of the biomarkers identified may also help improve our understanding of CAV pathophysiology.