The effect of exercise training on the course of cardiac troponin T and i levels: Three independent training studies

With the introduction of high-sensitive assays, cardiac troponins became potential biomarkers for risk stratification and prognostic medicine. Observational studies have reported an inverse association between physical activity and basal cardiac troponin levels. However, causality has never been demonstrated. This study investigated whether basal cardiac troponin concentrations are receptive to lifestyle interventions such as exercise training. Basal high-sensitive cardiac troponin T ( cTnT ) and I ( cTnI ) were monitored in two resistance-type exercise training programs ( 12-week ( study 1 ) and 24-week ( study 2 ) ) in older adults ( ≥65 years ). In addition, a retrospective analysis for high sensitive troponin I in a 24-week exercise controlled trial in ( pre )frail older adults was performed ( study 3 ). In total, 91 subjects were included in the final data analyses. There were no significant changes in cardiac troponin levels over time in study 1 and 2 ( study 1: cTnT −0.13 ( −0.33–+0.08 ) ng/L/12-weeks, cTnI −0.10 ( −0.33–+0.12 ) ng/L/12-weeks; study 2: cTnT −1.99 ( −4.79–+0.81 ) ng/L/24-weeks, cTnI −1.59 ( −5.70–+2.51 ) ng/L/24-weeks ). Neither was there a significant interaction between training and the course of cardiac troponin in study 3 ( p = 0.27 ). In conclusion, this study provides no evidence that prolonged resistance-type exercise training can modulate basal cardiac troponin levels

Genetic factors involved in EBV-postitive and EBV-negative Hodgkin lymphoma susceptibility : role of HLA-A and chemokine polymorphisms

Bij de ontwikkeling van Hodgkin lymfomen (lymfeklierkanker) spelen behalve immuno­logische factoren ook genetische en omgevingsfactoren een rol. De meest belangrijke omgevingsfactor is het Epstein Barr Virus (EBV). Normaal herkent het afweersysteem cellen die met EBV zijn geïnfecteerd en worden de geïnfecteerde cellen uitgeschakeld. Deze herkenning door het afweersysteem is voornamelijk erfelijk bepaald en zogenoemde Human Leucocyte Antigen (HLA)-componenten spelen hierbij een rol. Promovendus Marijke Niens onderzocht welke genen uit het HLA-gebied en welke uit het DNA-gebied met de chemokines TARC en MDC geassocieerd zijn met HL. De resultaten van het onderzoek suggereren dat personen die het HLA-A type *02 dragen een verlaagd risico hebben op het krijgen van EBV-positieve Hodgkin lymfomen. Dragers van HLA-A type *01 hebben waarschijnlijk een verhoogd risico. De concentraties van TARC en MDC zijn sterk verhoogd in serum van een grote meerderheid van de patiënten. In een kleine groep patiënten is aangetoond dat de concentratie van deze chemokines afneemt na behandeling. De bevindingen tonen aan dat beide chemokines mogelijk gebruikt kunnen worden als serum markers om de efficiëntie van de behandeling te controleren.

Bridging Mice to Men: Using HLA Transgenic Mice to Enhance the Future Prediction and Prevention of Autoimmune Type 1 Diabetes in Humans.

Similar to the vast majority of cases in humans, the development of type 1 diabetes (T1D) in the NOD mouse model is due to T-cell mediated autoimmune destruction of insulin producing pancreatic β cells. Particular major histocompatibility complex (MHC) haplotypes (designated HLA in humans; and H2 in mice) provide the primary genetic risk factor for T1D development. It has long been appreciated that within the MHC, particular unusual class II genes contribute to the development of T1D in both humans and NOD mice by allowing for the development and functional activation of β cell autoreactive CD4 T cells. However, studies in NOD mice have revealed that through interactions with other background susceptibility genes, the quite common class I variants (K(d), D(b)) characterizing this strain\u27s H2 (g7) MHC haplotype aberrantly acquire an ability to support the development of β cell autoreactive CD8 T cell responses also essential to T1D development. Similarly, recent studies indicate that in the proper genetic context some quite common HLA class I variants also aberrantly contribute to T1D development in humans. This review focuses on how humanized HLA transgenic NOD mice can be created and used to identify class I dependent β cell autoreactive CD8 T cell populations of clinical relevance to T1D development. There is also discussion on how HLA transgenic NOD mice can be used to develop protocols that may ultimately be useful for the prevention of T1D in humans by attenuating autoreactive CD8 T cell responses against pancreatic β cells. Methods Mol Biol 2016; 1438:137-5

Serum chemokine levels in Hodgkin lymphoma patients: Highly increased levels of CCL17 and CCL22

Hodgkin lymphoma (HL) is characterized by a minority of neoplastic Hodgkin-Reed Sternberg (HRS) cells surrounded by a non-neoplastic reactive infiltrate. As immunological mechanisms appear to be crucial in classical HL pathogenesis, altered serum chemokine levels might be related to disease activity. Serum levels of nine chemokines were examined in 163 untreated HL patients and 334 controls. We investigated single nucleotide polymorphisms (SNPs) for association with serum CCL17 (thymus and activation-regulated chemokine, TARC) levels and HL susceptibility. Serum CCL17 and CCL22 (macrophage-derived chemokine, MDC) levels were significantly increased in 82% and 57% of the HL patients. Nodular sclerosis cases showed increased serum CCL17 and CCL22 levels (P <0.001) and serum levels were correlated with Ann Arbor stage. Of nine patients with pre- and post-treatment serum samples, the majority showed decreased CCL17 and CCL22 levels after treatment. HRS cells expressed CCL17 and CCL22 in 77% and 75% of 74 cases. Three SNPs showed a trend of increased serum CCL17 levels with minor alleles in controls, but were not associated with HL susceptibility. CCL17 and CCL22 were the only chemokines with increased serum levels in the vast majority of HL patients, which provides further insight into the molecular mechanism(s) leading to infiltrations of reactive lymphocytes in HL