Role of microRNAs in immunity and organ transplantation.

Organ transplantation has evolved rapidly and there is now widespread use of donated organs for the treatment of end-stage organ failure. Although the therapeutic options achieving long-term graft survival have improved, acute and chronic rejections are still a major problem. Studies to identify noninvasive biomarkers for rejection and underlying molecular events have increased significantly in the past decade, but a major breakthrough is still missing. The recent discovery of small regulatory RNA molecules (microRNAs) resulted in a new and improved understanding of the mechanisms of gene regulation and also led to the development of the first new microRNA (miRNA)-based therapies. miRNAs are endogenous, single-stranded RNAs consisting of about 19-25 noncoding nucleotides, which have an important role in regulating gene expression. Additionally, circulating miRNAs that might be useful as novel disease biomarkers were detected. Here, we summarise current knowledge about the role of miRNAs in immunology and transplantation medicine and their role as potential biomarkers. We also focus on the molecular mechanisms and therapeutic implications of the use of miRNA-based therapeutic strategies to improve long-term allograft survival.

Minimal change nephrotic syndrome in an 82 year old patient following a tetanus-diphteria-poliomyelitis-vaccination.

BACKGROUND: The most common cause of idiopathic nephrotic syndrome in children and younger adults is the minimal change nephrotic syndrome (MCNS). In the elderly MCNS is relatively uncommon. Over the last decade some reports suggest a rare but possible association with the administration of various vaccines. CASE PRESENTATION: A 82-year old Caucasian female presented with pronounced nephrotic syndrome (proteinuria of 7.1 g/d, hypoproteinemia of 47 g/l). About six weeks prior to admission, she had received a combination vaccination for tetanus, diphtheria and poliomyelitis as a booster-vaccination from her general practitioner. The renal biopsy revealed typical minimal change lesions. She responded well to the initiated steroid treatment. As through physical examination as well as extensive laboratory and imaging studies did neither find any evidence for malignancies nor infections we suggest that the minimal change nephrotic syndrome in this patient might be related to the activation of the immune system triggered by the vaccination. CONCLUSION: Our case as well as previous anecdotal reports suggests that vaccination and the resulting stimulations of the immune system might cause MCNS and other severe immune-reactions. Increased awareness in that regard might help to expand the database of those cases.