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The “Exposome” is a concept that indicates the set of exposures to which a human is subjected during their lifetime. These factors influence the health state of individuals and can drive the development of Noncommunicable Diseases (NCDs). Artificial Intelligence (AI) allows one to analyze large amounts of data in a short time. As such, several authors have used AI to study the relationship between exposome and chronic diseases. Under such premises, this study reviews the use of AI in analyzing the exposome to understand its role in the development of chronic diseases, focusing on how AI can identify patterns in exposure-related data and support prevention strategies. To achieve this, we carried out a search on multiple databases, including PubMed, ScienceDirect, and SCOPUS, from 1 January 2019 to 31 May 2023, using the MeSH terms (exposome) and (‘Artificial Intelligence’ OR ‘Machine Learning’ OR ‘Deep Learning’) to identify relevant studies on this topic. After completing the identification, screening, and eligibility assessment, a total of 18 studies were included in this literature review. According to the search, most authors used supervised or unsupervised machine learning models to study multiple exposure factors’ role in the risk of developing cardiovascular, metabolic, and chronic respiratory diseases. In some more recent studies, authors also used deep learning. Furthermore, the exposome analysis is useful to study the risk of developing neuropsychiatric disorders or evaluating pregnancy outcomes and child growth. Understanding the role of the exposome is pivotal to overcome the classic concept of a single exposure/disease. The application of AI allows one to analyze multiple environmental risks and their combined effects on health conditions. In the future, AI could be helpful in the prevention of chronic diseases, providing new diagnostic, therapeutic, and follow-up strategies.

In recent years, cancer management has benefitted from new effective treatments, including immunotherapy. While these therapies improve cancer survival rates, they can alter immune responses and cause long-term side effects, of which gonadotoxic effects and the potential impact on male and female fertility are growing concerns. Immunotherapies, such as immune checkpoint inhibitors, immunomodulators, monoclonal antibodies, and CAR-T, can lead to elevated levels of proinflammatory cytokines and immune-related adverse events that may exacerbate fertility problems. Immunotherapy-related inflammation, characterized by cytokine imbalances and the activation of pathways such as AMPK/mTOR, has been implicated in the mechanisms of fertility impairment. In men, hypospermatogenesis and aspermatogenesis have been observed after treatment with immune checkpoint inhibitors, by direct effects on the gonads, particularly through the inhibition of cytotoxic T lymphocyte antigen-4. In women, both damage to ovarian reserves, recurrent pregnancy loss, and implantation failure have been documented, secondary to a complex interplay between immune cells, such as T cells and uterine NK cells. In this review, the impact of immunotherapy on fertility in patients with hematological cancers was analyzed. While this area is still underexplored, fertility preservation methods remain crucial. Future studies should investigate immunotherapy’s effects on fertility and establish standardized preservation protocols.

The synergic role of vitamin D and the intestinal microbiota in the regulation of the immune system has been thoroughly described in the literature. Vitamin D deficiency and intestinal dysbiosis have shown a pathogenetic role in the development of numerous immune-mediated and allergic diseases. The physiological processes underlying aging and sex have proven to be capable of having a negative influence both on vitamin D values and the biodiversity of the microbiome. This leads to a global increase in levels of systemic inflammatory markers, with potential implications for all immune-mediated diseases and allergic conditions. Our review aims to collect and analyze the relationship between vitamin D and the intestinal microbiome with the immune system and the diseases associated with it, emphasizing the effect mediated by sexual hormones and aging.

Introduction: The impact of COVID-19 pandemic represents a serious challenge for ‘frail’ patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic. Patients and method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines. Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p

Lipid metabolism is intrinsically linked to tumorigenesis. And one of the most important characteristics of cancer is the modification of lipid metabolism and its correlation with oncogenic signaling pathways within the tumors. Because lipids function as signaling molecules, membrane structures, and energy sources, lipids are essential to the development of cancer. Above all, the proper immune response of tumor cells depends on the control of lipid metabolism. Changes in metabolism can modify systems that regulate carcinogenesis, such as inflammation, oxidative stress, and angiogenesis. The dependence of various malignancies on lipid metabolism varies. This review delves into the modifications to lipid metabolism that take place in cancer, specifically focusing on multiple myeloma. The review illustrates how changes in different lipid pathways impact the growth, survival, and drug-responsiveness of multiple myeloma cells, in addition to their interactions with other cells within the tumor microenvironment. The phenotype of malignant plasma cells can be affected by lipid vulnerabilities, and these findings offer a new avenue for understanding this process. Additionally, they identify novel druggable pathways that have a major bearing on multiple myeloma care.

Vitamin D (VD) is a fat-soluble vitamin considered essential for human health, and its levels are associated with the function and composition of the intestinal microbiome [...]

Objectives To better define the spectrum of new-onset post-COVID-19 and post-COVID-19 vaccine inflammatory rheumatic diseases (IRD) from a large multicentric observational study.Methods Consecutive cases of IRD encountered during a 12-month period and satisfying one of the following inclusion criteria: (a) onset of the rheumatic manifestations within 4 weeks from SARS-CoV-2 infection or (b) onset of the rheumatic manifestations within 4 weeks from the administration of one of the COVID-19 vaccines ws recruited.Results The final analysis cohort comprised 267 patients, of which 122 (45.2%) in the post-COVID-19 and 145 (54.8%) in the postvaccine cohort. Distribution of IRD categories differed between the two cohorts: the post-COVID-19 cohort had a higher percentage of patients classified as having inflammatory joint diseases (IJD, 52.5% vs 37.2%, p=0.013) while the post-vaccine cohort had a higher prevalence of patients classified as polymyalgia rheumatica (PMR, 33.1% vs 21.3%, p=0.032). No differences were detected in the percentage of patients diagnosed with connective tissue diseases (CTD 19.7% vs 20.7%, p=0.837) or vasculitis (6.6% vs 9.0%, p=0.467). Despite the short follow-up period, IJD and PMR patients’ response to first-line therapy was favourable, with both groups achieving a drop in baseline disease activity scores of ~30% and ~70% respectively.Conclusion Our article reports the largest cohort published to date of new-onset IRD following SARS-CoV-2 infection or COVID-19 vaccines. Although causality cannot be ascertained, the spectrum of possible clinical manifestations is broad and includes IJD, PMR, CTD and vasculitis.

Objective To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort.Methods Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets.Results Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud’s phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1–16.5) than lcSSc (2 years, IQR 0–7), and dcSSc (1 year, IQR 0–3) (p

Multiple sclerosis, a condition characterised by demyelination and axonal damage in the central nervous system, is due to autoreactive immune cells that recognise myelin antigens. Alteration of the immune balance can promote the onset of immune deficiencies, loss of immunosurveillance, and/or development of autoimmune disorders such as MS. Numerous enzymes, transcription factors, signal transducers, and membrane proteins contribute to the control of immune system activity. The “transcriptional machine” of eukaryotic cells is a complex system composed not only of mRNA but also of non-coding elements grouped together in the set of non-coding RNAs. Recent studies demonstrate that ncRNAs play a crucial role in numerous cellular functions, gene expression, and the pathogenesis of many immune disorders. The main purpose of this review is to investigate the role of circular RNAs, a previously unknown class of non-coding RNAs, in MS’s pathogenesis. CircRNAs influence post-transcriptional control, expression, and functionality of a microRNA and epigenetic factors, promoting the development of typical MS abnormalities such as neuroinflammation, damage to neuronal cells, and microglial dysfunction. The increase in our knowledge of the role of circRNAs in multiple sclerosis could, in the future, modify the common diagnostic–therapeutic criteria, paving the way to a new vision of this neuroimmune pathology.

During aging, the immune system (IS) undergoes remarkable changes known as immunosenescence, a multifactorial and dynamic phenomenon that affects both natural and acquired immunity and plays an important role in most chronic diseases in older people. Among the determinants of immunosenescence, we find a low-grade sterile chronic inflammation, known as “inflamm-aging”. This condition of chronic inflammation causes a progressive reduction in the ability to trigger antibody and cellular responses effective against infections and vaccinations. In this review, we wanted to explore the role of immunosenescence and inflamm-aging as determinants of the immunological aging process and predisposing viral infections phenomena, with a particular reference to cytomegalovirus (CMV), varicella zoster virus (VZV), influenza virus (IFV) diseases and SARS-CoV2. IS aging is also reflected in a reduction in the antibody response to vaccinations, hence there is a need to expand trials to elderly patients, in order to identify the most appropriate methods for developing effective and safe vaccination and preventive strategies.

Optimizing the functional status of patients of any age is a major global public health goal. Rehabilitation is a process in which a person with disabilities is accompanied to achieve the best possible physical, functional, social, intellectual, and relational outcomes. The Intermediate Care Unit within the O.U. of Geriatrics and Gerontology of the San Martino Hospital in Genoa is focused on the treatment and motor reactivation of patients with geriatric pathologies. The objective of this study was to identify which factor, among the characteristics related to the patient and those identified by the geriatric evaluation, had the greatest impact on rehabilitation outcomes. Our findings revealed significant correlations between the Barthel Index delta, the 4AT Screening Test, and the number of drugs taken. This association highlights the potential benefits of medication management in enhancing the overall well-being and functional abilities of frail older adults, despite the literature suggesting that polypharmacotherapy is associated with a reduction in functional status and an increase in mortality. These findings underscore the significance of a multidimensional geriatric assessment. Refining and optimising these multidisciplinary approaches is the objective of a more effective geriatric rehabilitation strategy.

Abstract Histamine is a monoamine synthesized from the amino acid histidine that is well-known for its role in IgE-mediated anaphylaxis but has shown pleiotropic effects on the immune system, especially in order to promote inflammatory responses. H1-receptor antagonist are common drugs used in mild/moderate allergic reactions whereas H2-receptor antagonist are commonly administered in gastric ulcer but showed some properties in allergy too. The EAACI guidelines for diagnosis and treatment of anaphylactic reactions recommend their use as third-line therapy in adjunct to H1-antagonists. The purpose of this article is to produce a complete summary of findings and evidence known so far about the usefulness of H2-receptor antagonist in allergic reactons.

Abstract The world is now experiencing its third major epidemic of coronavirus (CoV) infections began in Wuhan, Hubei, China, in late 2019 and named COVID-19. After an initial explosive outbreak of pneumonia of unknown etiology in China, the disease spread first to neighboring Asian countries and then worldwide. Patients with COVID-19 presented with a constellation of symptoms such as fever, dry cough, dyspnea, sore throat, and nasal congestion and radiological findings showed bilateral lung glassy opacities. Vitamin D has many mechanisms by which it reduces the risk of microbial infection and death, including physical barrier, cellular natural immunity, and adaptive immunity. Vitamin D supplementation has shown favorable effects in viral infections including influenza and HIV. The effects of vitamin D supplementation during covid 19 infection remain controversial. Looking ahead, clinical studies are needed to define better cut offs for vitamin D levels and, finally, which dosage is the best.

Abstract Tranexamic acid (TXA) is a synthetic lysine analogue that is well known as antifibrinolytic agent. It can reduce blood loss in clinical use, especially in conditions where fibrinolysis or hyperfibrinolysis are involved, such as trauma or surgery. Moreover, TXA has been approved as second-line prophylactic therapy for hereditary angioedema and further data have been published about a possible use of TXA as maintenance treatment for nonhistaminergic angioedema and treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors. TXA can be administered through several routes: orally, topically, or intravenously. Although, it is a drug with a very high safety profile, in few cases hypersensitivity reactions have been described occurring with different clinical manifestations. Ethamsylate can be an alternative in TXA sensitized patients. In this brief article we describe TXA adverse reactions and current protocols which have been proposed to help clinicians to diagnose TXA hypersensitivity.

Abstract Background Amebiasis is a rare condition in developed countries but epidemiologically growing. Clinical manifestation may range from asymptomatic to invasive disease, amoebic liver abscess being the most common manifestation. We report a peculiar case of left hepatic amoebic liver abscess in a patient without a well-known source of infection and presenting with left portal vein thrombosis. Case presentation Patient, working as longshoreman, presented with complaints of remittent-intermittent fever lasting from 2 weeks. Physical examination was normal. Blood tests showed mild anemia, neutrophilic leukocytosis and elevated inflammation markers. Chest x-rays was normal. Abdominal ultrasound showed multiple hypoechoic liver masses. CT-scan of abdomen showed enlarged left liver lobe due to the presence of large abscess cavity along with thrombosis of left portal vein. The indirect hemagglutination test for the detection of antibodies to Entamoeba histolytica (Eh) was positive. Ultrasound-guided percutaneous drainage revealed “anchovy sauce” pus. Metronidazole and a follow up imaging at 3 months showed resolution of abscess cavity. Conclusion This case shows that amoebic liver abscess is possible even in first world country patients without travel history. Left sided abscess and portal vein thrombosis are rare and hence reported.

Skin inflammation is a common underlying feature of atopic dermatitis, allergic contact dermatitis and chronic spontaneous urticaria. The pathogenetic mechanisms have not been fully elucidated. The purpose of this study was to examine whether miRNA, by regulating inflammatory mechanisms through the modulation of innate and adaptive immune responses, could play a major role in the pathogenesis of these skin conditions. We conducted a narrative review using the Pubmed and Embase scientific databases and search engines to find the most relevant miRNAs related to the pathophysiology, severity and prognosis of skin conditions. The studies show that miRNAs are involved in the pathogenesis and regulation of atopic dermatitis and can reveal an atopic predisposition or indicate disease severity. In chronic spontaneous urticaria, different miRNAs which are over-expressed during urticaria exacerbations not only play a role in the possible response to therapy or remission, but also serve as a marker of chronic autoimmune urticaria and indicate associations with other autoimmune diseases. In allergic contact dermatitis, miRNAs are upregulated in inflammatory lesions and expressed during the sensitization phase of allergic response. Several miRNAs have been identified as potential biomarkers of these chronic skin conditions, but they are also possible therapeutic targets.

Although immunotherapy is already a staple of cancer care, many patients may not benefit from these cutting-edge treatments. A crucial field of research now focuses on figuring out how to improve treatment efficacy and assess the resistance mechanisms underlying this uneven response. For a good response, immune-based treatments, in particular immune checkpoint inhibitors, rely on a strong infiltration of T cells into the tumour microenvironment. The severe metabolic environment that immune cells must endure can drastically reduce effector activity. These immune dysregulation-related tumour-mediated perturbations include oxidative stress, which can encourage lipid peroxidation, ER stress, and T regulatory cells dysfunction. In this review, we have made an effort to characterize the status of immunological checkpoints, the degree of oxidative stress, and the part that latter plays in determining the therapeutic impact of immunological check point inhibitors in different neoplastic diseases. In the second section of the review, we will make an effort to assess new therapeutic possibilities that, by affecting redox signalling, may modify the effectiveness of immunological treatment.

The airway epithelium, through pattern recognition receptors expressed transmembrane or intracellularly, acts as a first line of defense for the lungs against many environmental triggers. It is involved in the release of alarmin cytokines, which are important mediators of inflammation, with receptors widely expressed in structural cells as well as innate and adaptive immune cells. Knowledge of the role of epithelial cells in orchestrating the immune response and mediating the clearance of invading pathogens and dead/damaged cells to facilitate resolution of inflammation is necessary to understand how, in many chronic lung diseases, there is a persistent inflammatory response that becomes the basis of underlying pathogenesis. This review will focus on the role of pulmonary epithelial cells and of airway epithelial cell alarmins, in particular thymic stromal lymphopoietin (TSLP) and high mobility group box 1 (HMGB1), as key mediators in driving the inflammation of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), evaluating the similarities and differences. Moreover, emerging concepts regarding the therapeutic role of molecules that act on airway epithelial cell alarmins will be explored for a precision medicine approach in the context of pulmonary diseases, thus allowing the use of these molecules as possible predictive biomarkers of clinical and biological response.

Allergy is an inflammatory process determined by a cascade of immune events characterized by T-helper 2 lymphocytes polarization leading to interleukin-4 upregulation, IgE secretion, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, are known to play a key immunoregulatory role and their involvement in allergic diseases is supported by increasing literature data. HLA-G expression and secretion is specifically induced in peripheral blood mononuclear cells of allergic patients after in vitro incubation with the causal allergen. Elevated levels of soluble HLA-G molecules are detected in serum of patients with allergic rhinitis correlating with allergen-specific IgE levels, clinical severity, drug consumption and response to allergen-specific immunotherapy. HLA-G genetic polymorphisms confer susceptibility to allergic asthma development and high levels of soluble HLA-G molecules are found in plasma and bronchoalveolar lavage fluid of patients with allergic asthma correlating with allergen-specific IgE levels. Interestingly, allergic pregnant women have lower plasma sHLA-G levels than non-allergic women during the 3rd trimester of pregnancy and at delivery. Finally, in allergic patients with atopic dermatitis HLA-G molecules are expressed by T cells, monocytes-macrophages and Langerhans cells infiltrating the dermis. Although at present is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are specifically expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.

Patients with diffused Systemic Sclerosis (dSSc) are more subject to severe respiratory complications with higher rates of intensive care unit (ICU) admission. Vaccination represents the most effective means of prevention and care for frail patients, such as SSc patients, preventing infections, reducing mortality and morbidity, and granting a better quality of life. Both vaccinations against seasonal influenza and Streptococcus pneumoniae are currently recommended by the European League Against Rheumatism (EULAR) guidelines on vaccination. The aim of this study is to give an updated analysis on S. pneumoniae and seasonal influenza vaccination coverage in a cohort of 91 patients with SSc and to investigate demographic and clinical variables significantly related to vaccine acceptance. The correlation between vaccine administration and other factors was investigated using a binomial logistic regression to evaluate the adjusted odds ratio (aOR). The patients followed up in this study reached higher percentages than the general population, passing the 75% target for both influenza and anti-pneumococcal vaccinations and reaching for influenza vaccine coverage rates of 83.8% for subjects undergoing immunosuppressive therapies and 88.9% for elderly subjects. For the latter group, it is important to emphasize the strong correlation between older age groups and vaccination acceptance.

Chronic spontaneous urticaria (CSU) is defined as the almost daily occurrence of widespread wheals, angioedema, or both, for more than 6 weeks. It affects 1–2% of the general population, with a higher prevalence in female patients, and is more frequent patients over 20 years of age. More than half of all cases of chronic idiopathic urticaria are thought to occur due to an autoimmune mechanism, specifically the production of autoantibodies against the high-affinity immunoglobulin E (IgE) receptor (FcεRI). The quality of life in these patients is often greatly compromised, also due to the onset of comorbidities represented by other autoimmune diseases, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, celiac disease, and type 1 diabetes, among others. This review aimed to analyze the close correlation between CSU and some autoimmune and autoinflammatory diseases, in order to encourage a multidisciplinary and multimorbid approach to the patient affected by CSU, which allows not only control of the natural course of the disease, but also any associated comorbidities.

Vitamin D (VD) is a fat-soluble hormone that plays a fundamental role not only in calcium homeostasis and bone metabolism, but also has anti-inflammatory and antioxidant properties, acting on both innate and adaptive immunity [...]

Inflammaging is a low degree of chronic and systemic tissue inflammation associated with aging, and is intimately linked to pro-inflammatory mediators. These substances are involved in the pathogenesis of chronic inflammatory diseases and related psychopathological symptoms. When inflammation and aging affect the brain, we use the term neuro-inflammaging. In this review, we focused on the neuro-inflammatory process typical of advanced ages and the related psychopathological symptoms, with particular attention to understanding the immune-pathogenetic mechanisms involved and the potential use of immunomodulatory drugs in the control of clinical psychological signs. Inflammation and CNS were demonstrated being intimately linked in the neuro-inflammatory loop. IL-1, IL-6, TNF-a, COX and PGE are only partially responsible. BBB permeability and the consequent oxidative stress resulting from tissue damage make the rest. Some authors elaborated the “theory of cytokine-induced depression”. Inflammation has a crucial role in the onset symptoms of psychopathological diseases as it is capable of altering the metabolism of biogenic monoamines involved in their pathogenesis. In recent years, NSAIDs as an adjunct therapy in the treatment of relevant psychopathological disorders associated with chronic inflammatory conditions demonstrated their efficacy. Additionally, novel molecules have been studied, such as adalimumab, infliximab, and etanercept showing antidepressant and anxiolytic promising results. However, we are only at the beginning of a new era characterized by the use of biological drugs for the treatment of inflammatory and autoimmune diseases, and this paper aims to stimulate future studies in such a direction.

The immune system is made up by an extremely composite group of cells, whose regulated and harmonious activity is fundamental to maintain health. The mast cells are an essential effector of inflammatory response which is characterized by a massive release of mediators accumulated in cytoplasmic secretory granules. However, beyond the effects on immune response, mast cells can modify bone metabolism and are capable of intervening in the genesis of pathologies such as osteoporosis and osteopenia. Vitamin D is recognized to induce changes in bone metabolism, but it is also able to influence immune response, suppressing mast cell activation and IgE synthesis from B cells and increasing the number of dendritic cells and IL-10-generating regulatory T cells. Vitamin D deficit has been reported to worsen sensitization and allergic manifestations in several different experimental models. However, in clinical situations, contradictory findings have been described concerning the correlation between allergy and vitamin D deficit. The aim of this review was to analyze the close relationships between mast cells and vitamin D, which contribute, through the activation of different molecular or cellular activation pathways, to the determination of bone pathologies and the onset of allergic diseases.

ObjectiveTo identify the existence of a correlation among the various organs affected, focusing primarily on immuno-dermatological aspects, and to create a risk prediction model of organ-specific complications.Material and MethodsFifty-two patients with stable scleroderma, followed between 2015 and 2019, were investigated through an extensive multidisciplinary evaluation in the last year.ResultsPatients with lung involvement presented a worse degree of skin fibrosis than patients without it (p

Adjuvant treatment of operated melanoma has deeply changed in the last few years with the introduction of immune-checkpoint inhibitors and BRAF/MEK inhibitors. Sarcoidosis is a systemic inflammatory disease causing non-caseous granulomatous reactions. Sarcoid-like granulomatous reactions have been reported in patients with advanced melanoma, mostly related to immunotherapy with immune-checkpoint inhibitors. We report a case of a 38-year-old woman with stage III operated melanoma treated with adjuvant BRAF plus MEK inhibitors, who developed sarcoidosis-like syndrome with systemic involvement, resolved after discontinuation of treatment. The occurrence of immune-related toxicity with the use of MAPK inhibitors supports the hypothesis that this class of drugs may also have an immunological effect, and that the long-term efficacy of adjuvant MAPK inhibitors may be due to their immunological function.

HLA-G is a HLA class Ib antigen that possesses immunomodulatory properties. HLA-G-expressing CD4+ and CD8+ T lymphocytes, NK cells, monocytes, and dendritic cells with immunoregulatory functions are present in small percentages of patients with physiologic conditions. Quantitative and qualitative derangements of HLA-G+ immune cells have been detected in several conditions in which the immune system plays an important role, such as infectious, neoplastic, and autoimmune diseases as well as in complications from transplants and pregnancy. These observations strongly support the hypothesis that HLA-G+ immune cells may be implicated in the complex mechanisms underlying the pathogenesis of these disorders.

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Interleukin (IL)-33 is a key cytokine involved in type-2 immunity and allergic airway disease. At the level of lung epithelial cells, where it is clearly expressed, IL-33 plays an important role in both innate and adaptive immune responses in mucosal organs. It has been widely demonstrated that in the course of respiratory virus infections, the release of IL-33 increases, with consequent pro-inflammatory effects and consequent exacerbation of the clinical symptoms of chronic respiratory diseases. In our work, we analyzed the pathogenetic and prognostic involvement of IL-33 during the main respiratory viral infections, with particular interest in the recent SARS-CoV-2virus pandemic and the aim of determining a possible connection point on which to act with a targeted therapy that is able to improve the clinical outcome of patients.

Systemic sclerosis (SSc) is a rare autoimmune inflammatory rheumatic disease. The prevalence of SSc ranges from 7 to 700 cases per million worldwide. Due to multiple organ involvement and constant inflammatory state, this group of patients presents an increased risk of infectious diseases. This paper aimed to gather the up-to-date evidence on vaccination strategies for patients with SSc and to be a useful tool for the prevention and management of infectious diseases. The authors conducted a scoping review in which each paragraph presents data on a specific vaccine’s safety, immunogenicity, and efficacy. The work deals with the following topics: SARS-CoV-2, seasonal influenza, S. pneumoniae, HAV, HBV, HZV, N. meningitidis, H. influenzae, HPV, and diphtheria-tetanus-pertussis.

The “cytokine storm” (CS) consists of a spectrum of different immune dysregulation disorders characterized by constitutional symptoms, systemic inflammation and multiorgan dysfunction triggered by an uncontrolled immune response. Particularly in respiratory virus infections, the cytokine storm plays a primary role in the pathogenesis of respiratory disease and the clinical outcome of respiratory diseases, leading to complications such as alveolar edema and hypoxia. In this review, we wanted to analyze the different pathogenetic mechanisms involved in the various respiratory viral pandemics (COVID-19; SARS; MERS; H1N1 influenza A and Spanish flu) which have affected humans in this and last century, with particular attention to the phenomenon of the “cytokine storm” which determines the clinical severity of the respiratory disease and consequently its lethality.

Systemic sclerosis (scleroderma, SSc) is an autoimmune connective tissue disease characterized by excessive production of collagen and multiorgan involvement. Scleroderma patients are at increased risk of influenza complications and pneumonia; thus, vaccinations are recommended. This systematic review evaluated the influenza and pneumococcus vaccination coverage for SSc patients. We included all studies from Pubmed reporting on influenza and pneumococcal vaccination rate in Scleroderma patients up to May 2021. The 14 studies thus selected identified a suboptimal vaccination rate in autoimmune and SSc patients, ranging from 28 to 59% for the flu vaccine, and from 11 to 58% for the pneumo vaccine in absence of specific vaccination campaigns, variously considering also other variables such as age, gender, vaccination settings, and possible vaccination campaigns. We also considered the reasons for low coverage and the approaches that might increase the vaccination rates. A lack of knowledge about the importance of vaccination in these patients and their doctors underlined the need to increase the awareness for vaccination in this patients’ category. Current guidelines recommend vaccination in elderly people and people affected by particular conditions that widely overlap with SSc, yet autoimmune diseases are not always clearly mentioned. Improving this suboptimal vaccination rate with clear guidelines is crucial for SSc patients and for clinicians to immunize these categories based principally on the pathology, prior to the age. Recommendations by the immunologist and the direct link to the vaccine providers can highly improve the vaccine coverage.

Basophils and mast cells are among the principal inducers of Th2 responses and have a crucial role in allergic and anti-parasitic protective immunity. Basophils can function as antigen-presenting cells that bind antigens on their surface and boost humoral immune responses, inducing Th2 cell differentiation. Their depletion results in lower humoral memory activation and greater infection susceptibility. Basophils seem to have an active role upon immune response to SARS-CoV-2. In fact, a coordinate adaptive immune response to SARS-CoV-2 is magnified by basophils. It has been observed that basophil amount is lower during acute disease with respect to the recovery phase and that the grade of this depletion is an important determinant of the antibody response to the virus. Moreover, mast cells, present in a great quantity in the nasal epithelial and lung cells, participate in the first immune response to SARS-CoV-2. Their activation results in a hyperinflammatory syndrome through the release of inflammatory molecules, participating to the “cytokine storm” and, in a longer period, inducing pulmonary fibrosis. The literature data suggest that basophil counts may be a useful prognostic tool for COVID-19, since their reduction is associated with a worse prognosis. Mast cells, on the other hand, represent a possible therapeutic target for reducing the airway inflammation characteristic of the hyperacute phase of the disease.

Introduction: Systemic sclerosis (SSc) is a systemic immune-mediated disease, featuring fibrosis of the skin and organs, and has the greatest mortality among rheumatic diseases. The nervous system involvement has recently been demonstrated, although actual lung involvement is considered the leading cause of death in SSc and, therefore, should be diagnosed early. Pulmonary function tests are not sensitive enough to be used for screening purposes, thus they should be flanked by other clinical examinations; however, this would lead to a risk of overtesting, with considerable costs for the health system and an unnecessary burden for the patients. To this extent, Machine Learning (ML) algorithms could represent a useful add-on to the current clinical practice for diagnostic purposes and could help retrieve the most useful exams to be carried out for diagnostic purposes. Method: Here, we retrospectively collected high resolution computed tomography, pulmonary function tests, esophageal pH impedance tests, esophageal manometry and reflux disease questionnaires of 38 patients with SSc, applying, with R, different supervised ML algorithms, including lasso, ridge, elastic net, classification and regression trees (CART) and random forest to estimate the most important predictors for pulmonary involvement from such data. Results: In terms of performance, the random forest algorithm outperformed the other classifiers, with an estimated root-mean-square error (RMSE) of 0.810. However, this algorithm was seen to be computationally intensive, leaving room for the usefulness of other classifiers when a shorter response time is needed. Conclusions: Despite the notably small sample size, that could have prevented obtaining fully reliable data, the powerful tools available for ML can be useful for predicting early lung involvement in SSc patients. The use of predictors coming from spirometry and pH impedentiometry together might perform optimally for predicting early lung involvement in SSc.

Diagnosis of idiopathic mediastinal fibrosis was done by exclusion in a 54-year-old woman with dyspnoea, chest pain, cough and fatigue showing positivity of 2-deoxy-2-[18F]fluoro-D-glucose positron-emission tomography/computed tomography total body imaging which turned out to normal after six and eighteen months of prednisone and pirfernidone treatment. Keywords: Positron-emission tomography/computed tomography (PET/CT), Idiopathic mediastinal fibrosis

Vitamin D is a lipo-soluble hormone well known for its effects on calcium homeostasis and bone metabolism. Recently, there has been growing interest in the extraskeletal effects of vitamin D. In particular, recent studies have highlighted how vitamin D plays a fundamental role in immunomodulation processes in the context of both innate and adaptive immunity, with consequent anti-inflammatory and anti-oxidant effect in different immune-mediated pathologies, such as systemic sclerosis, psoriasis, atopic dermatitis and rheumatoid arthritis; as well as in various pro-inflammatory processes affecting the airways, including chronic rhinosinusitis with (CRSwNP) or without (CRSsNP) nasal polyposis. We analyze the role of vitamin D in the genesis and progression of CRSwNP/sNP and its supplementation as a safe and valid therapeutic strategy capable of improving the clinical outcome of standard therapies.

Vitamin D (VD) and micronutrients, including folic acid, are able to modulate both the innate and the adaptive immune responses. Low VD and folic acid levels appear to promote cognitive decline as in Alzheimer’s disease (AD). A machine learning approach was applied to analyze the impact of various compounds, drawn from the blood of AD patients, including VD and folic acid levels, on the Mini-Mental State Exam (MMSE) in a cohort of 108 patients with AD. The first analysis was aimed at predicting the MMSE at recruitment, whereas a second investigation sought to predict the MMSE after a 4 year follow-up. The simultaneous presence of low levels of VD and folic acid allow to predict MMSE, suggestive of poorer cognitive function. Such results suggest that the low levels of VD and folic acid could be associated with more severe cases of cognitive impairment in AD. It could be hypothesized that simultaneous supplementation of VD and folic acid could slow down the progression of cerebral degeneration at least in a subset of AD individuals.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by complex pathophysiology and heterogeneous clinical picture. Belimumab is the first biological therapy licensed for SLE. We report the case of a 24 years old woman affected by a severe form of systemic lupus erythematosus with arthritis, muscle weakness, cervical lymphadenopathy, cutaneous involvement, fever, leukopenia, low complement levels and positivity for anti-dsDNA antibodies. Treatment with high dose steroids, hydroxychloroquine, and mycophenolate mofetil did not induce remission and several disease flares were observed. Therapy with anti-BLys monoclonal antibody belimumab leads to a fast clinical and laboratory response and to stable remission lasting for 30 months allowing steroid tapering to very low maintenance dose.

Systemic sclerosis (SSc) is the connective tissue disease with the highest mortality and patients with chronic inflammatory immune-mediated diseases are at high risk of acquiring infections as they are often treated with immunosuppressive or biological drugs. This study, conducted among the patients followed by our clinical immunology, part of the Internal Medicine Department in the Ospedale Policlinico San Martino, Genoa, northwest Italy, has set itself the primary objective of analyzing the vaccine uptake and the vaccination coverage against both seasonal influenza and S. pneumoniae in a cohort of patients with SSc. We evaluated the influenza and pneumococcal vaccination rate among various subgroups of patients and the source of the recommendation for vaccination. We evaluated the vaccination rate changes between the two years considered in our study. We also calculated a binomial logistic regression between vaccination acceptance and clinical and demographics characteristics of the patients to evaluate the adjusted odds ratio (OR) of each factor on vaccination. The vaccination coverage that resulted was significantly higher than in other similar studies. Age over 65 years old, interstitial lung disease, and ongoing immunosuppressive therapy were significantly related with acceptance to both vaccinations using univariate analyses, but the multivariate logistic regression found a significant correlation only with the age and therapy factors.

Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.

Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.