Austria, check your Czech media frames!

Empirische Untersuchung des medialen Image von Österreich in Tschechien nach dem EU-Beitritt Tschechiens. Untersuchungszeitraum: 2006 und 2008. Untersuchungsgegenstand: tschechische Printmedien. Methode: Medieninhaltsanalyse. Theoretisch gestützt durch Framing-Ansatz. Entwicklung des sog. Fünf-Stufen-Framing-Modells zur Erhebung des medialen Image von Ländern. Vergleichende Perspektive.Empirical research on the image of Austria in Czech print media after the Czech Republic joined the EU. Research period: 2006 and 2008. Method: Media content analysis. Applied theory: Framing/Frames. Result: For international media comparison universally applicable “five steps framing model” was developed

From a Biomarker to Targeting in a Proof-Of-Concept Trial

Background There is high medical need for safe long-term immunosuppression monotherapy in kidney transplantation. Selective targeting of post-transplant alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global T cell depletion may allow safe drug minimization, however, it is unsolved what might be the best maintenance monotherapy. Methods In this open, prospective observational single-centre trial, 20 primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by 5 mg/kg Infliximab (d2). For 14 days all patients received only tacrolimus, then they were allocated to either receive tacrolimus (TAC, n = 13) or sirolimus (SIR, n = 7) monotherapy, respectively. Protocol biopsies and extensive immune monitoring were performed and patients were followed-up for 60 months. Results TAC-monotherapy resulted in excellent graft survival (5yr 92%, 95%CI: 56.6–98.9) and function, normal histology, and no proteinuria. Immune monitoring revealed low intragraft inflammation (urinary IP-10) and hints for the development of operational tolerance signature in the TAC- but not SIR-group. Remarkably, the TAC-monotherapy was successful in all five presensitized (ELISPOT+) patients. However, recruitment into SIR-arm was stopped (after n = 7) because of high incidence of proteinuria and acute/chronic rejection in biopsies. No opportunistic infections occurred during follow-up. Conclusions In conclusion, our novel fast-track TAC- monotherapy protocol is likely to be safe and preliminary results indicated an excellent 5-year outcome, however, a full–scale study will be needed to confirm our findings. Trial Registration EudraCT Number: 2006-003110-1

Intrarenal Complement System Transcripts in Chronic Antibody-Mediated Rejection and Recurrent IgA Nephropathy in Kidney Transplantation

Background: The complement system activation and regulation have been linked to post-transplant pathologies including chronic antibody mediated rejection (cAMR) and the recurrence of IgA nephropathy (ReIgAN) but distinct mechanisms remain to be elucidated.Methods: In this retrospective single center study, the outcome of kidney transplantation was studied in 150 patients with late histological diagnosis to be either cAMR or ReIgAN, 14 stable kidney grafts at 3 months and finally 11 patients with native kidney IgAN nephropathy. To study a role of complement cascade and regulation in cAMR and ReIgAN, the RNA was extracted from available frozen kidney biopsy samples and using RT-qPCR transcripts of 11 target genes along with clinical data were determined and compared with stable grafts at 3 months protocol biopsies or IgAN native kidney nephropathy. Immunohistologically, CD46 (MCP), and C5 proteins were stained in biopsies.Results: Interestingly, there were no differences in kidney graft survival between cAMR and ReIgAN since transplantation. cAMR was associated with significantly higher intragraft transcripts of C3, CD59, and C1-INH as compared to ReIgAN (p < 0.05). When compared to normal stable grafts, cAMR grafts exhibited higher C3, CD55, CD59, CFH, CFI, and C1-INH (p < 0.01). Moreover, ReIgAN was associated with the increase of CD46, CD55, CD59 (p < 0.01), and CFI (p < 0.05) transcripts compared with native kidney IgAN. Rapid progression of cAMR (failure at 2 years after biopsy) was observed in patients with lower intrarenal CD55 expression (AUC 0.77, 78.6% sensitivity, and 72.7 specificity). There was highly significant association of several complement intrarenal transcripts and the degree of CKD regardless the diagnosis; C3, CD55, CFH, CFI, and C1-INH expressions positively correlated with eGFR (for all p < 0.001). Neither the low mRNA transcripts nor the high mRNA transcripts biopsies were associated with distinct trend in MCP or C5 proteins staining.Conclusions: The intrarenal complement system transcripts are upregulated in progressively deteriorated kidney allografts

Sequential Targeting of CD52 and TNF Allows Early Minimization Therapy in Kidney Transplantation: From a Biomarker to Targeting in a Proof-Of-Concept Trial.

There is high medical need for safe long-term immunosuppression monotherapy in kidney transplantation. Selective targeting of post-transplant alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global T cell depletion may allow safe drug minimization, however, it is unsolved what might be the best maintenance monotherapy.In this open, prospective observational single-centre trial, 20 primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by 5 mg/kg Infliximab (d2). For 14 days all patients received only tacrolimus, then they were allocated to either receive tacrolimus (TAC, n = 13) or sirolimus (SIR, n = 7) monotherapy, respectively. Protocol biopsies and extensive immune monitoring were performed and patients were followed-up for 60 months.TAC-monotherapy resulted in excellent graft survival (5yr 92%, 95%CI: 56.6-98.9) and function, normal histology, and no proteinuria. Immune monitoring revealed low intragraft inflammation (urinary IP-10) and hints for the development of operational tolerance signature in the TAC- but not SIR-group. Remarkably, the TAC-monotherapy was successful in all five presensitized (ELISPOT+) patients. However, recruitment into SIR-arm was stopped (after n = 7) because of high incidence of proteinuria and acute/chronic rejection in biopsies. No opportunistic infections occurred during follow-up.In conclusion, our novel fast-track TAC-monotherapy protocol is likely to be safe and preliminary results indicated an excellent 5-year outcome, however, a full-scale study will be needed to confirm our findings.EudraCT Number: 2006-003110-18

Distribution of patients in SIR and TAC groups depending on the pretransplant donor specific T-cell alloimmune response assessed by IFN-γ Elispot.

<p>Negative group: <20 spots/ 300 000 PBMC; positive group: >20 spots/ 300 000 PBMC.</p

List of B cell associated genes found to be differentially expressed within the particular group comparison.

<p>Annotation data are from <a href="http://www.uniprot.org/" target="_blank">http://www.uniprot.org/</a> and <a href="http://www.genecards.org/" target="_blank">http://www.genecards.org/</a>. In Tacrolimus/Sirolimus comparison fold change was calculated from gene expression medians of all measured time-points in particular groups. In rejecting and non-rejecting patients only samples collected at later time points (M2, M3, M6 and M12) were used to calculate medians of gene expression.</p

Validation of microarray analysis of blood samples by qRT-PCR of graft biopsies.

<p>The comparison of TAC- and SIR- group of patients and of patients with /without rejection event within 12 months posttransplant. All data are presented as mean±SEM. P values shown under the graphs indicate statistically significant difference in gene expression calculated by GLM mixed model.</p

Consort 2010 flow diagram.

<p>Consort 2010 flow diagram.</p

Validation of microarray analysis by qRT-PCR of blood samples. The comparison of TAC- and SIR- group of patients.

<p>All data are presented as mean±SEM. Statistically significant difference in gene expression within the whole study period was calculated by GLM mixed model. ** p<0.05, *** p<0.001.</p

Heat map of B-cell specific genes differentially expressed between TAC (violet) and SIR-group (yellow) with stronger expression in TAC samples.

<p>Heat map of B-cell specific genes differentially expressed between TAC (violet) and SIR-group (yellow) with stronger expression in TAC samples.</p