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Immunological abnormalities associated with pathological conditions, such as higher infection rates, inflammatory diseases, cancer or cardiovascular events are common in patients with panic disorder. In the present study, T cell receptor excision circles (TRECs), Forkhead-Box-Protein P3 gene (FOXP3) methylation of regulatory T cells (Tregs) and relative telomere lengths (RTLs) were investigated in a total and subsamples of 131 patients with panic disorder as compared to 131 age- and sex-matched healthy controls in order to test for a potential dysfunction and premature aging of the immune system in anxiety disorders. Significantly lower TRECs (p = 0.004) as well as significant hypermethylation of the FOXP3 promoter region (p = 0.005) were observed in female (but not in male) patients with panic disorder as compared to healthy controls. No difference in relative telomere length was discerned between patients and controls, but significantly shorter telomeres in females, smokers and older persons within the patient group. The presently observed reduced TRECs in panic disorder patients and FOXP3 hypermethylation in female patients with panic disorder potentially reflect impaired thymus and immunosuppressive Treg function, which might partly account for the known increased morbidity and mortality of anxiety disorders conferred by e.g. cancer and cardiovascular disorders.

Introduction: Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications., Methodology: The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts., Results: Here we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (>90%) and specificity (>60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation., Conclusion: These results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia.

Novel prognostic markers for progression of kidney disease are needed to distinguish patients who might benefit from a more aggressive nephroprotective therapy. Expression of the proteoglycan versican was evaluated in renal transcriptomics profiles and in an independent set of 74 renal biopsies. Versican levels were correlated to histologic damage scores and to renal outcome, and versican expression and regulation was evaluated in vitro. In transcriptomics profiles of renal tissue versican was positively correlated with (i) histological parameters in kidney biopsies, (ii) progressive decline of renal function in proteinuric kidney diseases, and (iii) impaired renal function and histology scores in diabetic nephropathy. In an independent cohort of 74 biopsies of glomerular diseases renal RNA levels of versican isoforms V0 and V1, but not V2 and V3 correlated significantly with creatinine after a mean follow up time of 53 months. Versican isoforms V0 and V1 together with serum creatinine at time of biopsy and the degree of glomerulosclerosis predicted 20% and 24% of the variability of creatinine at follow up, which was significantly more than serum creatinine and histological parameters alone (16%). However, when patients with acute kidney failure at time of biopsy (n = 5) were excluded, the additive predictive value of versican V1 was only marginally higher (35%) than creatinine and glomerulosclerosis alone (34%). Versican isoforms V0 and V1 were primarily expressed in vitro in proximal tubule cells and in fibroblasts. The results in humans were confirmed in three rodent models of kidney disease, in which renal versican expression was significantly upregulated as compared to corresponding controls. These data show for the first time an association of renal versican isoform V0 and V1 expression with progressive renal disease.