RNA Profiling in Human and Murine Transplanted Hearts: Identification and Validation of Therapeutic Targets for Acute Cardiac and Renal Allograft Rejection.

Acute cellular rejection (ACR) is the adverse response of the recipient's immune system against the allogeneic graft. Using human surveillance endomyocardial biopsies (EMBs) manifesting ACR and murine allogeneic grafts, we profiled implicated microRNAs (miRs) and mRNAs. MiR profiling showed that miR-21, -142-3p, -142-5p, -146a, -146b, -155, -222, -223, and -494 increased during ACR in humans and mice, whereas miR-149-5p decreased. mRNA profiling revealed 70 common differentially regulated transcripts, all involved in immune signaling and immune-related diseases. Interestingly, 33 of 70 transcripts function downstream of IL-6 and its transcription factor spleen focus forming virus proviral integration oncogene (SPI1), an established target of miR-155, the most upregulated miR in human EMBs manifesting rejection. In a mouse model of cardiac transplantation, miR-155 absence and pharmacological inhibition attenuated ACR, demonstrating the causal involvement and therapeutic potential of miRs. Finally, we corroborated our miR signature in acute cellular renal allograft rejection, suggesting a nonorgan specific signature of acute rejection. We concluded that miR and mRNA profiling in human and murine ACR revealed the shared significant dysregulation of immune genes. Inflammatory miRs, for example miR-155, and transcripts, in particular those related to the IL-6 pathway, are promising therapeutic targets to prevent acute allograft rejection.

Diagnosis and immunosuppressive treatment of inflammatory cardiomyopathy: a case report.

Objectives: Definite diagnosis of myocarditis requires an endomyocardial biopsy (EMB) showing an inflammatory infiltrate. However, there are important limitations on establishing the diagnosis solely upon histological criteria. The main objective of this case report is to highlight the difficulty of diagnosis, but also to evaluate treatment in virus-negative inflammatory cardiomyopathy.Case report: We present the case of a 53-year-old man with an inflammatory cardiomyopathy based on cardiac magnetic resonance (CMR) findings consistent with extensive myocardial inflammation and a significantly depressed left ventricular ejection fraction (LVEF). Treatment with immunosuppressive therapy resulted in improvement of cardiac function and performance status, while also eliminating the need for ICD implantation.Conclusion: Cardiac magnetic resonance (CMR) has a high diagnostic accuracy and has become the primary diagnostic tool for noninvasive assessment of suspected myocarditis. EMBs should be analyzed using immunohistochemistry and viral polymerase chain reaction to increase the diagnostic sensitivity of histology. Immunosuppressive therapy should be considered in virus-negative inflammatory cardiomyopathy.

A case of HELLP syndrome: an immuno-"logical" approach.

We report on a 27-year-old woman who developed severe arterial hypertension on a background of general malaise within 48 hours after vaginal delivery, suggesting severe acute-onset pre-eclampsia. Concomitant biochemical observations of haemolysis, elevated liver tests and low platelets lead to the diagnosis of (post-partum) HELLP syndrome. Our patient was transferred immediately to the intensive care unit (ICU), where she underwent plasmapheresis in combination with intravenous glucocorticoids, nicardipine and labetalol. Our patient recovered fully after three plasmapheresis sessions. Genetic testing of mutations responsible for complement deficits was negative.