Obesity is a global health problem with a broad set of comorbidities, such as malnutrition, metabolic syndrome, diabetes, systemic hypertension, heart failure, and kidney failure. This review ...describes recent findings of neuroimaging and two studies of cell density regarding the roles of overnutrition-induced hypothalamic inflammation in neurodegeneration. These studies provided consistent evidence of smaller cortical thickness or reduction in the gray matter volume in people with overweight and obesity; however, the investigated brain regions varied across the studies. In general, bilateral frontal and temporal areas, basal nuclei, and cerebellum are more commonly involved. Mechanisms of volume reduction are unknown, and neuroinflammation caused by obesity is likely to induce neuronal loss. Adipocytes, macrophages of the adipose tissue, and gut dysbiosis in overweight and obese individuals result in the secretion of the cytokines and chemokines that cross the blood-brain barrier and may stimulate microglia, which in turn also release proinflammatory cytokines. This leads to chronic low-grade neuroinflammation and may be an important factor for apoptotic signaling and neuronal death. Additionally, significant microangiopathy observed in rat models may be another important mechanism of induction of apoptosis. Neuroinflammation in neurodegenerative diseases (such as Alzheimer’s and Parkinson’s diseases) may be similar to that in metabolic diseases induced by malnutrition. Poor cognitive performance, mainly in executive functions, in individuals with obesity is also discussed. This review highlights the neuroinflammatory and neurodegenerative mechanisms linked to obesity and emphasizes the importance of developing effective prevention and treatment intervention strategies for overweight and obese individuals.
Autoimmune diseases, including autoimmune endocrine diseases (AIED), are thought to develop following environmental exposure in patients with genetic predisposition. The severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2) and vaccines against it could represent new environmental triggers for AIED. We report a patient, with history of vitiligo vulgaris and 8 years of type 2 diabetes, who came to our institution because of fever, weight loss, asthenia and thyrotoxicosis occurred 4 weeks later the administration of BNT162B2 (Pfizer-BioNTech) SARS-CoV-2 vaccine. Clinical, biochemical and instrumental work-up demonstrated Graves’ disease and autoimmune diabetes mellitus. The occurrence of these disorders could be explained through different mechanism such as autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome), mRNA “self-adjuvant” effect, molecular mimicry between human and viral proteins and immune disruption from external stimuli. However further studies are needed to better understand the underlying pathogenesis of AIED following SARS-CoV-2 vaccine.
•SARS-CoV-2 vaccination could trigger autoimmune endocrine disease.•Fifth case of Graves' disease following SARS-CoV-2 vaccination.•First description of type 1 diabetes following SARS-CoV-2 vaccination.•ASIA syndrome and molecular mimicry are potential mechanisms.
Hashimoto's thyroiditis (HT), the most frequent autoimmune thyroid disorders (AITDs), is the leading cause of hypothyroidism in the iodine-sufficient areas of the world. About 20–30% of patients ...suffers from HT, whose cause is thought to be a combination of genetic susceptibility and environmental factors that causes the loss of immunological tolerance, with a consequent autoimmune attack to the thyroid tissue and appearance of the disease.
The pathologic features of lymphocytic infiltration, especially of T cells, and follicular destruction are the histological hallmark of autoimmune thyroiditis (AIT), that lead to gradual atrophy and fibrosis. An important role in the immune-pathogenesis of AITDs is due to chemokines and cytokines.
In about 20% of patients, AITDs are associated with other organ specific/systemic autoimmune disorders.
Many studies have demonstrated the relationship between papillary thyroid cancer and AITD.
The treatment of hypothyroidism, as result of AIT, consists in daily assumption of synthetic levothyroxine.
Th1 Chemokines in Autoimmune Endocrine Disorders Fallahi, Poupak; Ferrari, Silvia Martina; Ragusa, Francesca ...
The journal of clinical endocrinology and metabolism,
04/2020, Letnik:
105, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract
Context
The CXC chemokine receptor CXCR3 and its chemokines CXCL10, CXCL9, and CXCL11 are implicated in the pathogenesis of autoimmune diseases. Here, we review these chemokines in ...autoimmune thyroiditis (AT), Graves disease (GD), thyroid eye disease (TED), type 1 diabetes (T1D), and Addison’s disease (AAD).
Evidence Acquisition
A PubMed review of the literature was conducted, searching for the above-mentioned chemokines in combination with AT, GD, TED, T1D, and AAD.
Evidence Synthesis
Thyroid follicular cells in AT and GD, retroorbital cells in TED (fibroblasts, preadipocytes, myoblasts), β cells and islets in T1D, and adrenal cells in AAD respond to interferon-γ (IFN-γ) stimulation producing large amounts of these chemokines. Furthermore, lymphocytes and peripheral blood mononuclear cells (PBMC) are in part responsible for the secreted Th1 chemokines. In AT, GD, TED, T1D, and AAD, the circulating levels of these chemokines have been shown to be high. Furthermore, these chemokines have been associated with the early phases of the autoimmune response in all the above-mentioned disorders. High levels of these chemokines have been associated also with the “active phase” of the disease in GD, and also in TED. Other studies have shown an association with the severity of hypothyroidism in AD, of hyperthyroidism in GD, with severity of TED, or with fulminant T1D.
Conclusion
The reviewed data have shown the importance of the Th1 immune response in different endocrine autoimmune diseases, and many studies have suggested that CXCR3 and its chemokines might be considered as potential targets of new drugs for the treatment of these disorders.
A hallmark of cancer is the ability of tumor cells to avoid immune destruction. Activated immune cells in tumor microenvironment (TME) secrete proinflammatory cytokines and chemokines which foster ...the proliferation of tumor cells. Specific antigens expressed by cancer cells are recognized by the main actors of immune response that are involved in their elimination (immunosurveillance). By the recruitment of immunosuppressive cells, decreasing the tumor immunogenicity, or through other immunosuppressive mechanisms, tumors can impair the host immune cells within the TME and escape their surveillance. Within the TME, cells of the innate (e.g., macrophages, mast cells, neutrophils) and the adaptive (e.g., lymphocytes) immune responses are interconnected with epithelial cancer cells, fibroblasts, and endothelial cells via cytokines, chemokines, and adipocytokines. The molecular pattern of cytokines and chemokines has a key role and could explain the involvement of the immune system in tumor initiation and progression. Thyroid cancer-related inflammation is an important target for diagnostic procedures and novel therapeutic strategies. Anticancer immunotherapy, especially immune checkpoint inhibitors, unleashes the immune system and activates cytotoxic lymphocytes to kill cancer cells. A better knowledge of the molecular and immunological characteristics of TME will allow novel and more effective immunotherapeutic strategies in advanced thyroid cancer.
We evaluated SARS-CoV-2 antibody response in voluntary blood donors in Italy at different timepoints. Immediately after lockdown easing, 908/25,657 donors (3.5%) had low IgG titers against ...nucleocapsid. In the next 2 years, titers increased despite few COVID-19 symptoms. On multivariate analysis, allergic rhinitis was associated with reduced risk for symptomatic COVID-19.
Immune checkpoint inhibitors (ICI) foster T lymphocytes to fight cancer, but they can also trigger immune-related adverse events (irAE) in various organs, including thyroid dysfunction that can ...manifest itself in terms of both hyperthyroidism and hypothyroidism or subclinical disease.
Based on previous observations, this study evaluated the impact of oncological immunotherapy on the development of thyroid dysfunction in a cohort of patients treated with ICI at our institution.
We collected 10 cases of thyroid irAE that emerged from 24 cancer patients treated with immunotherapy, belonging to a cohort of 120 patients who were sent to our clinic by the Oncology Department of our institution, between December 2016 and March 2020.
From the analysis of the data, thyroid irAEs emerged after a median time of 9 weeks, and they occurred mainly in females. Regardless of the initial presentation (thyroiditis with thyrotoxicosis, hypothyroidism, or worsening of the previous subclinical hypothyroidism), later all patients developed persistent hypothyroidism which required hormone replacement therapy with levothyroxine. This finding was confirmed by a statistically significant increase in the median value of TSH (thyroid-stimulating hormone) between the pre-ICI treatment and subsequent phases and, for the first time, by a reduction in the median value of the thyroid volume estimated by neck ultrasound, a sign of destructive thyroiditis.
Our results confirm that patients undergoing immunotherapy should be monitored for potential thyroid dysfunction with biochemical assessments and changes in thyroid volume estimated by ultrasound could be helpful in the diagnostic work-up.
Cognitive reserve (CR) is the adaptability of cognitive processes that helps to explain differences in the susceptibility of cognitive or daily functions to resist the onslaught of brain-related ...injury or the normal aging process. The underlying brain mechanisms of CR studied through electroencephalogram (EEG) are scarcely reported. To our knowledge, few studies have considered a combination of exclusively dynamic proxy measures of CR. We evaluated the association of CR with cognition and resting-state EEG in older adults using three of the most frequently used dynamic proxy measures of CR: verbal intelligence, leisure activities, and physical activities. Multiple linear regression analyses with the CR proxies as independent variables and cognitive performance and the absolute power (AP) on six resting-state EEG components (beta, alpha1, alpha2, gamma, theta, and delta) as outcomes were performed. Eighty-eight healthy older adults aged 60–77 (58 female) were selected from previous study data. Verbal intelligence was a significant positive predictor of perceptual organization, working memory, processing speed, executive functions, and central delta power. Leisure activities were a significant positive predictor of posterior alpha2 power. The dynamic proxy variables of CR are differently associated with cognitive performance and resting-state EEG. Implementing leisure activities and tasks to increase vocabulary may promote better cognitive performance through compensation or neural efficiency mechanisms.
The purpose of this study is to assess psychosocial risk across several pediatric medical conditions and test the hypothesis that different severe or chronic pediatric illnesses are characterized by ...disease specific enhanced psychosocial risk and that risk is driven by disease specific connectivity and interdependencies among various domains of psychosocial function using the Psychosocial Assessment Tool (PAT). In a multicenter prospective cohort study of 195 patients, aged 5-12, 90 diagnosed with acute lymphoblastic leukemia (ALL), 42 with epilepsy and 63 with asthma, parents completed the PAT2.0 or the PAT2.0 generic version. Multivariate analysis was performed with disease as factor and age as covariate. Graph theory and network analysis was employed to study the connectivity and interdependencies among subscales of the PAT while data-driven cluster analysis was used to test whether common patterns of risk exist among the various diseases. Using a network modelling approach analysis, we observed unique patterns of interconnected domains of psychosocial factors. Each pathology was characterized by different interdependencies among the most central and most connected domains. Furthermore, data-driven cluster analysis resulted in two clusters: patients with ALL (89%) mostly belonged to cluster 1, while patients with epilepsy and asthma belonged primarily to cluster 2 (83% and 82% respectively). In sum, implementing a network approach improves our comprehension concerning the character of the problems central to the development of psychosocial difficulties. Therapy directed at problems related to the most central domain(s) constitutes the more rational one because such an approach will inevitably carry over to other domains that depend on the more central function.
Cytokines and chemokines, hepatitis C virus (HCV) infection-induced, participate in viral control and liver damage. The complex cytokine network, operating during initial infection allows a ...coordinated and effective development of innate and adaptive immune responses. "HCV interferes with cytokines at various levels and escapes immune response by inducing a T helper (Th)2/T cytotoxic 2 cytokine profile". A predominance of the Th1 immune response (and related cytokines) has been evidenced in chronic hepatitis C infection and in extrahepatic manifestations. Interferon (IFN)-γ and IFN-γ-inducible chemokine (C-X-C motif) ligand (CXCL)9, -10 and -11 recruit inflammatory infiltrates into the liver parenchyma due to the incapability to control the infection process, resulting in extensive liver damage and liver cirrhosis. "The most important systemic HCV-related extrahepatic diseases - mixed cryoglobulinemia, lymphoproliferative disorders, diabetes and autoimmune thyroid disorders - are associated with a complex dysregulation of the cytokine/chemokine network and involve pro-inflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-α may result in viral clearance during persistent infection and reverts this process" reducing circulating CXCL10 levels. "Several studies have reported interleukin (IL)-28B polymorphisms, and circulating CXCL10, may be prognostic markers for HCV treatment efficacy in HCV infection". Other studies have also shown that HCV clearance by directly acting antiviral agents therapy decreases circulating CXCL10 levels. "Theoretically agents that selectively neutralize CXCL10 could increase patient responsiveness to traditional IFN-based HCV therapy", simultaneously reducing inflammatory immune cell activation.
PDF
