Role of molecular mimicry and polyclonal cell activation in the induction of pathogenic β2-glycoprotein I–directed immune response in Balb/c mice upon hyperimmunization with tetanus toxoid

It is known that tetanus toxoid (TTd)-hyperimmunization induces increased titer of sera β2-glycoprotein I (β2GPI)-specific antibodies (Abs) in Balb/c mice. The concentrations of such induced anti-β2GPI Abs as well as their pathogenic potential are strongly influenced by the context of TTd application. β2GPI-specific immune response is established as a part of TTd-specific immune response by molecular mimicry mechanism due to structural homology between TTd and β2GPI. This finding is supported by the following facts: (1) cross-reactive Abs that recognize both TTd and β2GPI epitopes are present in Balb/c mice sera; (2) anti-TTd Abs secretion in splenic cultures is induced after β2GPI stimulation and vice versa. However, analyses of (1) IL-10 production following in vitro stimulation of immunized Balb/c mice splenocytes by TTd, β2GPI or glutaraldehyde-treated β2GPI and (2) specific impact of ConA and agonists of TLR2, TLR4, and TLR9 on anti-TTd and autoreactive Abs secretion strongly imply that these two branches of the TTd-induced immune response do not use identical cell populations and are regulated in a different way. Results presented in this paper describe that structural homology between foreign and self-antigens could focus mounted autoreactive immune response toward specific self-structure, but the context of antigen application, including a history of previous immune stimulations and adjuvants applied together with the antigen, are the main factors which determine the outcome of the induced immune response.     

TNF-α and IL-1β sensitize human MSC for IFN-γ signaling and enhance neutrophil recruitment

During inflammatory processes, tissue environmental cues are influencing the immunoregulatory properties of tissue-resident mesenchymal stem/stromal cells (MSC). In this study, we elucidated one of the molecular and cellular responses of human MSC exposed to combinations of inflammatory cytokines. We showed that during multi-cytokine priming by TNF-α, IL-1β, and IFN-γ, IL-1β further augmented the well-established immunoregulatory activity induced by TNF-α/IFN-γ. On the molecular level, TNF-α and IL-1β enhanced the expression of IFN-γ receptor (IFN-γR) via NF 'kappa-light-chain-enhancer' of activated B-cells (NF-κΒ) signaling. In turn, enhanced responsiveness to IFN-γ stimulation activated STAT5 and p38-MAPK signaling. This molecular feedback resulted in an increased IL-8 release and augmented recruitment of polymorphonuclear granulocytes (PMN). Our study suggests the possibility that responses of MSC to multi-cytokine priming regimens may be exploited therapeutically to fine-tune inflammatory activity in tissues. This study elucidates molecular mechanisms underlying the immunological priming of mesenchymal stromal cells (MSC) and their interaction with neutrophils.     

Dark chocolate reduces endothelial dysfunction after successive breath-hold dives in cool water

Objective

The aim of this study is to observe the effects of dark chocolate on endothelial function after a series of successive apnea dives in non-thermoneutral water.

Methods

Twenty breath-hold divers were divided into two groups: a control group (8 males and 2 females) and a chocolate group (9 males and 1 female). The control group was asked to perform a series of dives to 20 m adding up to 20 min in the quiet diving pool of Conflans-Ste-Honorine (Paris, France), water temperature was 27 °C. The chocolate group performed the dives 1 h after ingestion of 30 g of dark chocolate. Flow-mediated dilatation (FMD), digital photoplethysmography, nitric oxide (NO), and peroxynitrite ONOO^?) levels were measured before and after each series of breath-hold dives.

Results

A significant decrease in FMD was observed in the control group after the dives (95.28 ± 2.9 % of pre-dive values, p < 0.001) while it was increased in the chocolate group (104.1 ± 2.9 % of pre-dive values, p < 0.01). A decrease in the NO level was observed in the control group (86.76 ± 15.57 %, p < 0.05) whereas no difference was shown in the chocolate group (98.44 ± 31.86 %, p > 0.05). No differences in digital photoplethysmography and peroxynitrites were observed between before and after the dives.

Conclusion

Antioxidants contained in dark chocolate scavenge free radicals produced during breath-hold diving. Ingestion of 30 g of dark chocolate 1 h before the dive can thus prevent endothelial dysfunction which can be observed after a series of breath-hold dives.     

Pyramidal lobe decreases endogenous TSH stimulation without impact on radio-iodine therapy outcome in patients with differentiated thyroid cancer

Objectives

The aim of the study was to assess the frequency of pyramidal lobe (PL) detected in iodine-131 (I-131) scans of thyroid bed in patients after thyroidectomy for differentiated thyroid cancer (DTC) and to investigate influence of PL on endogenous thyrotropin (TSH) stimulation as well as on the effects of the radio-iodine ablation in one-year follow-up.

Patients and methods

This study was designed as a retrospective analysis of 302 radio-iodine neck scans of patients thyroidectomized due to DTC. The study population was selected from patients with PL detected in thyroid bed scintigraphy. Patients without PL were included to the control group. The study and the control groups did not differ in age, sex of patients, histological type and stage of the DTC.

Results

Pyramidal lobes were found in 30.5% of all patients. Patients in the study group underwent repeat surgery more often than controls without PL. Preablative TSH level in patients with PL was statistically lower than in the control group, in contrast to free thyroid hormones, which were higher in patients with PL. Preablative and postablative TSH-stimulated thyroglobulin (Tg) and antibodies against thyroglobulin (TgAbs) were measured in both groups, and comparison did not reveal differences. Moreover, for the per-patient analysis, sites of uptake in whole body scintigraphy performed 1 year after radio-iodine remnant ablation (RRA) did not differ between the study and the control groups.

Conclusion

Pyramidal lobe decreases endogenous TSH stimulation without impact on radio-iodine therapy outcome in patients with DTC.     

Influenza vaccination coverage in children with inflammatory bowel disease

The aim of this study was to evaluate the influenza vaccination status among paediatric patients with inflammatory bowel disease (IBD) in Poland. This was a questionnaire‐based study. 242 patients with IBD and 142 controls were enrolled in the study. Of patients with IBD, 7·8% received an influenza vaccine, compared to 18·3% of controls (P = 0·0013). There were no statistically significant differences in time from IBD diagnosis, disease activity and in drugs, between vaccinated and non‐vaccinated IBD children. In conclusion, the data of our study demonstrate an alarmingly poor influenza vaccination status in the majority of children with IBD. Therefore, there is an unmet need to implement better influenza vaccination strategies for this group of patients.