Systemic sclerosis (SSc) is an autoimmune disease which is characterized by vasculopathy, tissue fibrosis and activation of the innate and adaptive immune system. Clinical features of the disease consists of skin thickening and internal organ involvement. Due to the heterogeneous nature of the disease it is difficult to predict disease progression and complications. Despite the discovery of novel autoantibodies associated with SSc, there is an unmet need for biomarkers for diagnosis, disease progression and response to treatment. To date, the use of single (surrogate) biomarkers for these purposes has been unsuccessful. Combining multiple biomarkers in to predictive panels or ultimately algorithms could be more precise. Given the limited therapeutic options and poor prognosis of many SSc patients, a better understanding of the immune-pathofysiological profiles might aid to an adjusted therapeutic approach. Therefore, we set out to explore immunological fingerprints in various clinically defined forms of SSc. We used multilayer profiling to identify unique immune profiles underlying distinct autoantibody signatures. These immune profiles could fill the unmet need for prognosis and response to therapy in SSc. Here, we present 3 pathophysiological fingerprints in SSc based on the expression of circulating antibodies, vascular markers and immunomodulatory mediators.
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From PLoS website: In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C), an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diindolylmethane (DIM). I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA), an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.
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From teh UU repository: "Background: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, there are some concerns regarding its safety and long-term efficacy. The use of non-digestible oligosaccharides might improve OIT efficacy since they are known to directly modulate intestinal epithelial and immune cells in addition to acting as prebiotics. Aim: To investigate whether a diet supplemented with plant-derived fructo-oligosaccharides (FOS) supports the efficacy of OIT in a murine cow's milk allergy model and to elucidate the potential mechanisms involved. Methods: After oral sensitization to the cow's milk protein whey, female C3H/HeOuJ mice were fed either a control diet or a diet supplemented with FOS (1% w/w) and received OIT (10 mg whey) 5 days a week for 3 weeks by gavage. Intradermal (i.d.) and intragastric (i.g.) challenges were performed to measure acute allergic symptoms and mast cell degranulation. Blood and organs were collected to measure antibody levels and T cell and dendritic cell populations. Spleen-derived T cell fractions (whole spleen-and CD25-depleted) were transferred to naive recipient mice to confirm the involvement of regulatory T cells (Tregs) in allergy protection induced by OIT + FOS. Results: OIT + FOS decreased acute allergic symptoms and mast cell degranulation upon challenge and prevented the challenge-induced increase in whey-specific IgE as observed in sensitized mice. Early induction of Tregs in the mesenteric lymph nodes (MLN) of OIT + FOS mice coincided with reduced T cell responsiveness in splenocyte cultures. CD25 depletion in OIT + FOS-derived splenocyte suspensions prior to transfer abolished protection against signs of anaphylaxis in recipients. OIT + FOS increased serum galectin-9 levels. No differences in short-chain fatty acid (SCFA) levels in the cecum were observed between the treatment groups. Concisely, FOS supplementation significantly improved OIT in the acute allergic skin response, %Foxp3+ Tregs and %LAP+ Th3 cells in MLN, and serum galectin-9 levels. Conclusion: FOS supplementation improved the efficacy of OIT in cow's milk allergic mice. Increased levels of Tregs in the MLN and abolished protection against signs of anaphylaxis upon transfer of CD25-depleted cell fractions, suggest a role for Foxp3+ Tregs in the protective effect of OIT + FOS. "
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Dit artikel onderzoekt immuniteit buiten de contouren van een menselijk lichaam en een biopolitiek kader in het plantwetenschappelijk materieel-discursief object van het superonkruid met zijn resistentie en tolerantie voor herbiciden. In plaats van categorisch aan te nemen dat alle vormen van immuniteit en immuunsystemen plaatsvinden binnen de abstracte categorie van het (menselijk) lichaam, besteedt het artikel aandacht aan de manier waarop het superonkruid als analytisch en synthetiserend brandpunt het concept van immuniteit gaat bevolken en erdoor bevolkt wordt. In het algemeen beweert de auteur dat de materiële dimensie van het superonkruid kan worden gezien als een uitbreiding van of aanvulling op noties van het individuele, autonome en begrensde menselijke lichaam, maar dat deze materiële dimensie ook zijn eigen subjectpositie kan ondermijnen. Door het concept van immuniteit los te koppelen van zijn 'oorsprong' in het menselijk lichaam, kunnen nieuwe ontologische gronden voor menselijke en niet-menselijke politieke ecologieën worden bedacht, met een andere vorm van belichaming, die noch negatief, noch bevestigend zijn.
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The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria. Nanomaterials (NMs) can enter the cavities intentionally for medical purposes, or unintentionally following environmental exposure; subsequent serosal inflammation and cancer (mesothelioma) has gained significant interest. However, reports on adverse effects of NMon ILCs and other components of the serosal immune systemare scarce or even lacking. As ILCs are crucial in the first defense against pathogenic viruses and bacteria, it is possible that serosal exposure to NMmay lead to a reduced resistance against pathogens. Additionally, affected serosal lymphoid tissues and cells may disturb adipose tissue homeostasis. This review aims to provide insight into key effects of NMon the serosal immune system.
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Objective: To explore the nature and extent of possible residual complaints among Dutch hypothyroid patients using thyroid replacement therapy, we initiated a comprehensive study measuring health-related quality of life (QoL), daily functioning, and hypothyroidism-associated symptoms in patients and control persons. Methods: An online survey measuring thyroid-specific QoL (ThyPRO), daily functioning, and hypothyroidismassociated symptoms (ThySHI) was distributed among treated hypothyroid patients and control individuals. The advertising text was formulated in an open-ended manner. Patients also provided their most recent thyroid blood values and their thyroid medication. Results: There was a large-sized impairment of QoL (Cohen’s d = 1.04, +93 % ThyPRO score) in hypothyroid patients on thyroid replacement therapy (n = 1195) as compared to controls (n = 236). Daily functioning was significantly reduced i.e., general health (-38 %), problems with vigorous- (+64 %) and moderate activities (+77 %). Almost 80 % of patients reported having complaints despite thyroid medication and in-range thyroid blood values, with 75 % expressing a desire for improved treatment options for hypothyroidism (total n = 1194). Hypothyroid patients experienced 2.8 times more intense hypothyroidism-associated symptoms than controls (n = 865, n = 203 resp). Patients’ median reported serum concentrations were: TSH 0.90 mU/L, FT4 17.0 pmol/L, and FT3 2.67 pmol/L, with 52 % having low T3 levels (<3.1 pmol/L). The QoL was not found to be related to age, sex, BMI, menopausal status, stress, serum thyroid parameters, the origin and duration of hypothyroidism, the type of thyroid medication, or the LT4 dose used. Conclusions: Our study revealed major reductions in quality of life and daily functioning, and nearly three times more intense hypothyroidism-associated symptoms in treated hypothyroid patients as compared to controls, despite treatment and largely in-range serum TSH/FT4 concentrations. The QoL was not associated with serum thyroid parameters. We recommend future research into the origin of persisting complaints and the development of improved treatment modalities for hypothyroidism.
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Sicca syndrome (dry mouth and dry eyes) occurs predominantly due to the side effects of medication, systemic diseases (Sjögren’s disease), and radiotherapy of the head and neck region. Sicca complaints decrease the quality of life, cause sleep disturbances, and affect overall health. This systematic literature review investigates the correlation and/or association between dry mouth and dry eyes. A comprehensive search was conducted through PubMed and Web of Science databases up to November 2024. English-language research studies investigating the association and/or correlation between dry mouth and dry eyes were included. Study quality was assessed using NIH quality assessment tools. Data on publication details, participant characteristics, assessment methods, and outcomes was extracted and synthesised based on the type of outcome (objective and/or subjective assessments) and cohort type.
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Cardiovascular disease (CVD) morbidity and mortality is highly prevalent in patients with rheumatoid arthritis (RA) with debilitating effects for the individual as well as significant healthcare impact. Current evidence demonstrates that engaging in aerobic and resistance exercise (i.e. structured physical activity) can significantly improve patient-reported and clinical index-assessed outcomes in RA. In addition to this, engagement in exercise programmes improves, in a dose-dependent manner, the risk of developing CVD as well as CVD symptoms and outcomes. The present narrative review uses evidence from systematic reviews and meta-analyses as well as controlled trials, to synthesize the current state-of-the-art on the potential effects of aerobic and resistance exercise on CVD risk factors as well as on cardiac and vascular function and structure in people with RA. Where there is a lack of evidence in RA to explain potential mechanisms, relevant studies from the general population are also discussed and linked to RA.
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Nationwide and across the globe, the quality, affordability, and accessibility of home-based healthcare are under pressure. This issue stems from two main factors: the rapidly growing ageing population and the concurrent scarcity of healthcare professionals. Older people aspire to live independently in their homes for as long as possible. Additionally, governments worldwide have embraced policies promoting “ageing in place,” reallocating resources from institutions to homes and prioritising home-based services to honour the desire of older people to continue living at home while simultaneously addressing the rising costs associated with traditional institutional care.Considering the vital role of district nursing care and the fact that the population of older people in need of assistance at home is growing, it becomes clear that district nursing care plays a crucial role in primary care. The aim of this thesis is twofold: 1) to strengthen the evidence base for district nursing care; and 2) to explore the use of outcomes for learning and improving in district nursing care. The first part of this thesis examines the current delivery of district nursing care and explores its challenges during the COVID-19 pandemic to strengthen the evidence base and get a better understanding of district nursing care. Alongside the goal of strengthening the evidence for district nursing care, the second part of this thesis explores the use of patient outcomes for learning and improving district nursing care. It focuses on nurse-sensitive patient outcomes relevant to district nursing care, their current measurement in practice, and what is needed to use outcomes for learning and improving district nursing practice.
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tIn this study we aimed to identify genes that are responsive to pertussis toxin (PTx) and might eventu-ally be used as biological markers in a testing strategy to detect residual PTx in vaccines. By microarrayanalysis we screened six human cell types (bronchial epithelial cell line BEAS-2B, fetal lung fibroblastcell line MRC-5, primary cardiac microvascular endothelial cells, primary pulmonary artery smooth mus-cle cells, hybrid cell line EA.Hy926 of umbilical vein endothelial cells and epithelial cell line A549 andimmature monocyte-derived dendritic cells) for differential gene expression induced by PTx. Imma-ture monocyte-derived dendritic cells (iMoDCs) were the only cells in which PTx induced significantdifferential expression of genes. Results were confirmed using different donors and further extendedby showing specificity for PTx in comparison to Escherichia coli lipopolysaccharide (LPS) and Bordetellapertussis lipo-oligosaccharide (LOS). Statistical analysis indicated 6 genes, namely IFNG, IL2, XCL1, CD69,CSF2 and CXCL10, as significantly upregulated by PTx which was also demonstrated at the protein levelfor genes encoding secreted proteins. IL-2 and IFN- gave the strongest response. The minimal PTx con-centrations that induced production of IL-2 and IFN- in iMoDCs were 12.5 and 25 IU/ml, respectively.High concentrations of LPS slightly induced IFN- but not IL-2, while LOS and detoxified pertussis toxindid not induce production of either cytokine. In conclusion, using microarray analysis we evaluated sixhuman cell lines/types for their responsiveness to PTx and found 6 PTx-responsive genes in iMoDCs ofwhich IL2 is the most promising candidate to be used as a biomarker for the detection of residual PTx.
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