@article{ZlamyAlmanzarParsonetal.2016, author = {Zlamy, Manuela and Almanzar, Giovanni and Parson, Walther and Schmidt, Christian and Leierer, Johannes and Weinberger, Birgit and Jeller, Verena and Unsinn, Karin and Eyrich, Matthias and W{\"u}rzner, Reinhard and Prelog, Martina}, title = {Efforts of the human immune system to maintain the peripheral CD8+ T cell compartment after childhood thymectomy}, series = {Immunity \& Ageing}, volume = {13}, journal = {Immunity \& Ageing}, number = {3}, doi = {10.1186/s12979-016-0058-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146497}, year = {2016}, abstract = {Background Homeostatic mechanisms to maintain the T cell compartment diversity indicate an ongoing process of thymic activity and peripheral T cell renewal during human life. These processes are expected to be accelerated after childhood thymectomy and by the influence of cytomegalovirus (CMV) inducing a prematurely aged immune system. The study aimed to investigate proportional changes and replicative history of CD8+ T cells, of recent thymic emigrants (RTEs) and CD103+ T cells (mostly gut-experienced) and the role of Interleukin-(IL)-7 and IL-7 receptor (CD127)-expressing T cells in thymectomized patients compared to young and old healthy controls. Results Decreased proportions of naive and CD31 + CD8+ T cells were demonstrated after thymectomy, with higher proliferative activity of CD127-expressing T cells and significantly shorter relative telomere lengths (RTLs) and lower T cell receptor excision circles (TRECs). Increased circulating CD103+ T cells and a skewed T cell receptor (TCR) repertoire were found after thymectomy similar to elderly persons. Naive T cells were influenced by age at thymectomy and further decreased by CMV. Conclusions After childhood thymectomy, the immune system demonstrated constant efforts of the peripheral CD8+ T cell compartment to maintain homeostasis. Supposedly it tries to fill the void of RTEs by peripheral T cell proliferation, by at least partly IL-7-mediated mechanisms and by proportional increase of circulating CD103+ T cells, reminiscent of immune aging in elderly. Although other findings were less significant compared to healthy elderly, early thymectomy demonstrated immunological alterations of CD8+ T cells which mimic features of premature immunosenescence in humans.}, language = {en} } @article{AlmanzarZlamyKoppelstaetteretal.2013, author = {Almanzar, Giovanni and Zlamy, Manuela and Koppelstaetter, Christian and Brunner, Andrea and Jeller, Verena and Duftner, Christina and Dejaco, Christian and Brunner, Juergen and Prelog, Martina}, title = {Increased replication of CD4+ naive T cells and changes in T cell homeostasis in a case of acute exacerbation of juvenile idiopathic arthritis: a case comparison study}, series = {Journal of Medical Case Reports}, journal = {Journal of Medical Case Reports}, doi = {10.1186/1752-1947-7-135}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96325}, year = {2013}, abstract = {Introduction Juvenile idiopathic arthritis is a heterogeneous T cell-mediated autoimmune disease with symptoms of premature aging of the immune system (immunosenescence). The present work is an investigation of immunosenescence parameters, such as quantity of naive and CD28- T cells, T cell receptor excision circles, relative telomere length and alterations of peripheral T cell replication, and was performed via comparison of a case of acute exacerbation of juvenile idiopathic arthritis against six patients with juvenile idiopathic arthritis with disease remission and six age-matched healthy donors over a follow-up course of 12 months. Case presentation Phenotypical T cell characterization and intracellular interferon γ, tumor necrosis factor α, and interleukin 2 production were studied in peripheral blood mononuclear cells from seven patients with juvenile idiopathic arthritis and six healthy control donors, with findings determined by flow cytometry. T cell receptor excision circles and relative telomere length quantification were performed on deoxyribonucleic acid isolated from naive (CD4+CD28+CD45RA+) T cells and investigated via reverse transcription polymerase chain reaction. Ki67 expression was studied by immunohistochemistry on naive T cells. The non-parametric Mann-Whitney U test and Wilcoxon test for two independent groups of variables were used to compare healthy donors with patients with juvenile idiopathic arthritis. During follow-up, patients with juvenile idiopathic arthritis showed lower total counts of naive and CD28-expressing T cells compared to healthy donors. Acute exacerbation led to low naive and CD28+ T cell populations and elevated proportions of Ki67-expressing CD4+ naive T cells. In conditions of exacerbation, T cell receptor excision circle numbers were in the lower range in patients with juvenile idiopathic arthritis and increased after follow-up. Healthy donors showed significantly higher relative telomere lengths compared to patients with juvenile idiopathic arthritis. Conclusions This investigation illustrates that the changes in T cell homeostasis in patients with juvenile idiopathic arthritis may be the result of several mechanisms, such as diminished thymus function and peripheral exertions to maintain the peripheral T cell pool. The results also demonstrate that hallmarks of immunosenescence such as decreased naive T cell levels and lower T cell receptor excision circle numbers can only be interpreted together with replication markers such as relative telomere length or Ki67 expression.}, language = {en} } @article{PrelogZlamyKofleretal.2013, author = {Prelog, Martina and Zlamy, Manuela and Kofler, Sabine and Orth, Dorothea and W{\"u}rzner, Reinhard and Heinz-Erian, Peter and Streng, Andrea}, title = {The impact of Rotavirus mass vaccination on hospitalization rates, nosocomial Rotavirus gastroenteritis and secondary blood stream infections}, series = {BMC Infectious Diseases}, journal = {BMC Infectious Diseases}, doi = {10.1186/1471-2334-13-112}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96147}, year = {2013}, abstract = {Background The aim of the study was to evaluate the effects of universal mass vaccination (UMV) against rotavirus (RV) on the hospitalization rates, nosocomial RV infections and RV-gastroenteritis (GE)-associated secondary blood stream infections (BSI). Methods The retrospective evaluation (2002-2009) by chart analysis included all clinically diagnosed and microbiologically confirmed RV-GE cases in a large tertiary care hospital in Austria. The pre-vaccination period (2002-2005) was compared with the recommended and early funded (2006-2007) and the funded (2008-2009) vaccination periods. Primary outcomes were RV-GE-associated hospitalizations, secondary outcomes nosocomial RV disease, secondary BSI and direct hospitalization costs for children and their accompanying persons. Results In 1,532 children with RV-GE, a significant reduction by 73.9\% of hospitalized RV-GE cases per year could be observed between the pre-vaccination and the funded vaccination period, which was most pronounced in the age groups 0-11 months (by 87.8\%), 6-10 years (by 84.2\%) and 11-18 years (88.9\%). In the funded vaccination period, a reduction by 71.9\% of nosocomial RV-GE cases per year was found compared to the pre-vaccination period. Fatalities due to nosocomial RV-GE were only observed in the pre-vaccination period (3 cases). Direct costs of hospitalized, community-acquired RV-GE cases per year were reduced by 72.7\% in the funded vaccination period. The reduction of direct costs for patients (by 86.9\%) and accompanying persons (86.2\%) was most pronounced in the age group 0-11 months. Conclusions UMV may have contributed to the significant decrease of RV-GE-associated hospitalizations, to a reduction in nosocomial RV infections and RV-associated morbidity due to secondary BSI and reduced direct hospitalization costs. The reduction in nosocomial cases is an important aspect considering severe disease courses in hospitalized patients with co-morbidities and death due to nosocomial RV-GE.}, language = {en} }