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Article ; Online: UV radiation and air pollution as drivers of major autoimmune conditions.

Piovani, Daniele / Brunetta, Enrico / Bonovas, Stefanos

2023 Volume 224, Page(s) 115449

Abstract: Autoimmune diseases comprise a very heterogeneous group of disorders characterized by disruptive immune responses against self-antigens, chronic morbidity and increased mortality. The incidence and prevalence of major autoimmune conditions are ... ...

Abstract	Autoimmune diseases comprise a very heterogeneous group of disorders characterized by disruptive immune responses against self-antigens, chronic morbidity and increased mortality. The incidence and prevalence of major autoimmune conditions are particularly high in the western world, at northern latitudes, and in industrialized countries. This study will mainly focus on five major autoimmune conditions, namely type 1 diabetes, multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, and autoimmune thyroid disorders. Epidemiological and experimental evidence suggests a protective role of sunlight exposure on the etiology of major autoimmune conditions mediated by the endogenous production of vitamin D and nitric oxide. A historical perspective shows how the rise of anthropogenic air pollutants is temporally associated with dramatic increases in incidence of these conditions. The scattering caused by ambient particulate matter and the presence of tropospheric ozone can reduce the endogenous production of vitamin D and nitric oxide, which are implicated in maintaining the immune homeostasis. Air pollutants have direct detrimental effects on the human body and are deemed responsible of an increasingly higher portion of the annual burden of human morbidity and mortality. Air pollution contributes in systemic inflammation, activates oxidative pathways, induces epigenetic alterations, and modulates the function and phenotype of dendritic cells, Tregs, and T-cells. In this review, we provide epidemiological and mechanistic insights regarding the role of UV-mediated effects in immunity and how anthropic-derived air pollution may affect major autoimmune conditions through direct and indirect mechanisms.
MeSH term(s)	Humans ; Ultraviolet Rays ; Nitric Oxide ; Air Pollution ; Air Pollutants ; Particulate Matter ; Autoimmune Diseases/etiology ; Vitamin D
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; Air Pollutants ; Particulate Matter ; Vitamin D (1406-16-2)
Language	English
Publishing date	2023-02-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2023.115449
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Article ; Online: UV radiation and air pollution as drivers of major autoimmune conditions

Piovani, Daniele / Brunetta, Enrico / Bonovas, Stefanos

Environmental Research. 2023, p.115449-

2023 , Page(s) 115449–

Abstract	Autoimmune diseases comprise a very heterogeneous group of disorders characterized by disruptive immune responses against self-antigens, chronic morbidity and increased mortality. The incidence and prevalence of major autoimmune conditions are particularly high in the western world, at northern latitudes, and in industrialized countries. This study will mainly focus on five major autoimmune conditions, namely type 1 diabetes, multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, and autoimmune thyroid disorders. Epidemiological and experimental evidence suggests a protective role of sunlight exposure on the etiology of major autoimmune conditions mediated by the endogenous production of vitamin D and nitric oxide. A historical perspective shows how the rise of anthropogenic air pollutants is temporally associated with dramatic increases in incidence of these conditions. The scattering caused by ambient particulate matter and the presence of tropospheric ozone can reduce the endogenous production of vitamin D and nitric oxide, which are implicated in maintaining the immune homeostasis. Air pollutants have direct detrimental effects on the human body and are deemed responsible of an increasingly higher portion of the annual burden of human morbidity and mortality. Air pollution contributes in systemic inflammation, activates oxidative pathways, induces epigenetic alterations, and modulates the function and phenotype of dendritic cells, Tregs, and T-cells. In this review, we provide epidemiological and mechanistic insights regarding the role of UV-mediated effects in immunity and how anthropic-derived air pollution may affect major autoimmune conditions through direct and indirect mechanisms.
Keywords	T-lymphocytes ; air ; air pollution ; epigenetics ; etiology ; homeostasis ; humans ; immunity ; industrialization ; inflammation ; insulin-dependent diabetes mellitus ; morbidity ; mortality ; nitric oxide ; ozone ; particulates ; phenotype ; protective effect ; research ; rheumatoid arthritis ; sclerosis ; troposphere ; ultraviolet radiation ; Risk factors ; Epidemiology ; Environmental medicine ; Ecotoxicology ; Immunology ; Autoimmunity
Language	English
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2023.115449
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Article ; Online: Autoinflammatory manifestations in adult patients.

Rodolfi, Stefano / Nasone, Irene / Folci, Marco / Selmi, Carlo / Brunetta, Enrico

Clinical and experimental immunology

2022 Volume 210, Issue 3, Page(s) 295–308

Abstract: Autoinflammatory diseases represent a family of immune-mediated conditions characterized by the unchecked activation of innate immunity. These conditions share common clinical features such as recurrent fever, inflammatory arthritis, and elevation of ... ...

Abstract	Autoinflammatory diseases represent a family of immune-mediated conditions characterized by the unchecked activation of innate immunity. These conditions share common clinical features such as recurrent fever, inflammatory arthritis, and elevation of acute phase reactants, in the absence of an identified infectious etiology, generally without detectable serum autoantibodies, with variable response to glucocorticoids and in some cases colchicine, which represented the mainstay of treatment until cytokine blockade therapies became available. The first autoinflammatory diseases to be described were monogenic disorders caused by missense mutations in inflammasome components and were recognized predominantly during childhood or early adulthood. However, the progress of genetic analyses and a more detailed immunological phenotyping capacity led to the discovery a wide spectrum of diseases, often becoming manifest or being diagnosed in the adult population. The beneficial role of targeting hyperinflammation via interleukin 1 in complex non-immune-mediated diseases is a field of growing clinical interest. We provide an overview of the autoinflammatory diseases of interest to physicians treating adult patients and to analyze the contribution of hyperinflammation in non-immune-mediated diseases; the result is intended to provide a roadmap to orient scientists and clinicians in this broad area.
MeSH term(s)	Humans ; Adult ; Hereditary Autoinflammatory Diseases/genetics ; Interleukin-1 ; Immunity, Innate ; Inflammasomes ; Arthritis
Chemical Substances	Interleukin-1 ; Inflammasomes
Language	English
Publishing date	2022-11-04
Publishing country	England
Document type	Journal Article
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxac098
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Article: A Comprehensive Approach to Urticaria: From Clinical Presentation to Modern Biological Treatments Through Pathogenesis.

Folci, Marco / Ramponi, Giacomo / Brunetta, Enrico

Advances in experimental medicine and biology

2021 Volume 1326, Page(s) 111–137

Abstract: Urticaria is characterized by the cutaneous presence of wheals (hives), angioedema or both. Acute and chronic urticaria are distinguished based on a duration of less or more than 6 weeks. Chronic urticaria can be further classified into a spontaneous ... ...

Abstract	Urticaria is characterized by the cutaneous presence of wheals (hives), angioedema or both. Acute and chronic urticaria are distinguished based on a duration of less or more than 6 weeks. Chronic urticaria can be further classified into a spontaneous form and several inducible types triggered by specific external stimuli. Lifetime prevalence of urticaria may be up to 20%, with the acute form being way more common than the chronic one. Exacerbating factors (e.g. infections, drugs, food) and immune system alterations have been investigated as main triggers of mast cell activation, which in turn leads to increased vascular permeability and extravasation of inflammatory cells. While diagnostic workup is focused upon history taking, several emerging biomarkers correlate with severity and/or prognosis of the disease and can be necessary to differentiate chronic spontaneous urticaria from other disorders, such as vasculitis and autoinflammatory diseases. Treatment of acute urticaria is based upon H1 antihistamines and short courses of steroids. While H1 antihistamines are also used in chronic spontaneous urticaria, omalizumab is the standard of care in patients who are unresponsive to these. Recently, several new drugs have entered clinical trials to offer a therapeutic possibility for patients unresponsive to omalizumab. Numerous target molecules, such as mediators of mast cells activation, are under investigation. Amongst these, new anti-IgE therapies and possibly IL-5 pathway blockade seem to have reached enough data to move to advanced clinical trials.
MeSH term(s)	Angioedema/drug therapy ; Anti-Allergic Agents/therapeutic use ; Chronic Disease ; Chronic Urticaria ; Humans ; Omalizumab/therapeutic use ; Urticaria/diagnosis ; Urticaria/drug therapy
Chemical Substances	Anti-Allergic Agents ; Omalizumab (2P471X1Z11)
Language	English
Publishing date	2021-01-09
Publishing country	United States
Document type	Journal Article
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/5584_2020_612
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Article ; Online: Serum ANCA as Disease Biomarkers: Clinical Implications Beyond Vasculitis.

Folci, Marco / Ramponi, Giacomo / Solitano, Virginia / Brunetta, Enrico

Clinical reviews in allergy & immunology

2021 Volume 63, Issue 2, Page(s) 107–123

Abstract: Usually associated with autoimmune diseases, anti-neutrophil cytoplasmic antibodies are also detected in other conditions, such as infections, malignancies, and after intake of certain drugs. Even if the mechanisms of production and their pathogenic role ...

Abstract	Usually associated with autoimmune diseases, anti-neutrophil cytoplasmic antibodies are also detected in other conditions, such as infections, malignancies, and after intake of certain drugs. Even if the mechanisms of production and their pathogenic role have not been fully elucidated yet, ANCA are widely recognized as a clinically alarming finding due to their association with various disorders. While ANCA target several autoantigens, proteinase-3, and myeloperoxidase are the ones proved to be most frequently related to chronic inflammation and tissue damage in murine models. Albeit these autoantibodies could be present as an isolated observation without any implications, ANCA are frequently used in clinical practice to guide the diagnosis in a suspect of small vessel vasculitis. Conditions that should prompt the clinician to test ANCA status range from various forms of lung disease to renal or peripheral nervous system impairment. ANCA positivity in the presence of an autoimmune disease, especially rheumatoid arthritis, or connective tissue diseases, is frequently correlated with more clinical complications and treatment inefficacy, even in the absence of signs of vasculitis. For this reason, it has been postulated that ANCA could represent the final expression of an immune dysregulation rather than a pathogenic event responsible for organs damage. Recently, it has also been proposed that ANCA specificity (PR3 or MPO) could possibly define ANCA-associated vasculitides better than clinical phenotype. This review aims at summarizing the latest advancements in the field of ANCA study and clinical interpretation.
MeSH term(s)	Animals ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis ; Antibodies, Antineutrophil Cytoplasmic ; Autoantibodies ; Autoantigens ; Biomarkers ; Humans ; Mice ; Myeloblastin ; Peroxidase
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Autoantibodies ; Autoantigens ; Biomarkers ; Peroxidase (EC 1.11.1.7) ; Myeloblastin (EC 3.4.21.76)
Language	English
Publishing date	2021-08-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1239045-8
ISSN	1559-0267 ; 1080-0549
ISSN (online)	1559-0267
ISSN	1080-0549
DOI	10.1007/s12016-021-08887-w
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Article: Evaluating Short-Term Tidal Flat Evolution Through UAV Surveys: A Case Study in the Po Delta (Italy)

Brunetta, Riccardo / Duo, Enrico / Ciavola, Paolo

Remote Sensing. 2021 June 13, v. 13, no. 12

2021

Abstract: The use of Unmanned Aerial Vehicles (UAV) on wetlands is becoming a common survey technique that is extremely useful for understanding tidal flats and salt marshes. However, its implementation is not straightforward because of the complexity of the ... ...

Abstract	The use of Unmanned Aerial Vehicles (UAV) on wetlands is becoming a common survey technique that is extremely useful for understanding tidal flats and salt marshes. However, its implementation is not straightforward because of the complexity of the environment and fieldwork conditions. This paper presents the morphological evolution of the Po della Pila tidal flat in the municipality of Porto Tolle (Italy) and discusses the reliability of UAV-derived Digital Surface Models (DSMs) for such environments. Four UAV surveys were performed between October 2018 and February 2020 on an 8 ha young tidal flat that was generated, amongst others, as a consequence of the massive sediment injection into the Po Delta system due to the floods of the 1950s and 1960s. The DSM accuracy was tested by processing (i.e., photogrammetry) diverse sets of pictures taken at different altitudes during the same survey day. The DSMs and the orthophotos show that the tidal flat is characterised by several crevasse splays and that the sediment provision depends strictly on the river. During the study period, the sediment budget was positive (gaining 800 m³/year and an average rate of vertical changes of 1.3 cm/year). Comparisons of DSMs demonstrated that neither lower flight altitudes (i.e., 20–100 m) nor the combination of more photos from different flights during the same surveys necessarily reduce the error in such environments. However, centimetric errors (i.e., RMSEs) are achievable flying at 80–100 m, as the increase of GCP (Ground Control Point) density is the most effective solution for enhancing the resolution. Guidelines are suggested for implementing high-quality UAV surveys in wetlands.
Keywords	case studies ; evolution ; flight ; orthophotography ; photogrammetry ; river deltas ; rivers ; sediments ; surveys ; Italy
Language	English
Dates of publication	2021-0613
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2513863-7
ISSN	2072-4292
ISSN	2072-4292
DOI	10.3390/rs13122322
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Evaluating Short-Term Tidal Flat Evolution Through UAV Surveys

Riccardo Brunetta / Enrico Duo / Paolo Ciavola

Remote Sensing, Vol 13, Iss 2322, p

A Case Study in the Po Delta (Italy)

2021 Volume 2322

Abstract	The use of Unmanned Aerial Vehicles (UAV) on wetlands is becoming a common survey technique that is extremely useful for understanding tidal flats and salt marshes. However, its implementation is not straightforward because of the complexity of the environment and fieldwork conditions. This paper presents the morphological evolution of the Po della Pila tidal flat in the municipality of Porto Tolle (Italy) and discusses the reliability of UAV-derived Digital Surface Models (DSMs) for such environments. Four UAV surveys were performed between October 2018 and February 2020 on an 8 ha young tidal flat that was generated, amongst others, as a consequence of the massive sediment injection into the Po Delta system due to the floods of the 1950s and 1960s. The DSM accuracy was tested by processing (i.e., photogrammetry) diverse sets of pictures taken at different altitudes during the same survey day. The DSMs and the orthophotos show that the tidal flat is characterised by several crevasse splays and that the sediment provision depends strictly on the river. During the study period, the sediment budget was positive (gaining 800 m 3 /year and an average rate of vertical changes of 1.3 cm/year). Comparisons of DSMs demonstrated that neither lower flight altitudes (i.e., 20–100 m) nor the combination of more photos from different flights during the same surveys necessarily reduce the error in such environments. However, centimetric errors (i.e., RMSEs) are achievable flying at 80–100 m, as the increase of GCP (Ground Control Point) density is the most effective solution for enhancing the resolution. Guidelines are suggested for implementing high-quality UAV surveys in wetlands.
Keywords	unmanned aerial vehicle ; tidal flats ; salt marshes ; wetlands ; geomorphological changes ; sedimentation rates ; Science ; Q
Subject code	333
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Eosinophils as Major Player in Type 2 Inflammation: Autoimmunity and Beyond.

Folci, Marco / Ramponi, Giacomo / Arcari, Ivan / Zumbo, Aurora / Brunetta, Enrico

Advances in experimental medicine and biology

2021 Volume 1347, Page(s) 197–219

Abstract: Eosinophils are a subset of differentiated granulocytes which circulate in peripheral blood and home in several body tissues. Along with their traditional relevance in helminth immunity and allergy, eosinophils have been progressively attributed ... ...

Abstract	Eosinophils are a subset of differentiated granulocytes which circulate in peripheral blood and home in several body tissues. Along with their traditional relevance in helminth immunity and allergy, eosinophils have been progressively attributed important roles in a number of homeostatic and pathologic situations. This review aims at summarizing available evidence about eosinophils functions in homeostasis, infections, allergic and autoimmune disorders, and solid and hematological cancers.Their structural and biological features have been described, along with their physiological behavior. This includes their chemokines, cytokines, granular contents, and extracellular traps. Besides, pathogenic- and eosinophilic-mediated disorders have also been addressed, with the aim of highlighting their role in Th2-driven inflammation. In allergy, eosinophils are implicated in the pathogenesis of atopic dermatitis, allergic rhinitis, and asthma. They are also fundamentally involved in autoimmune disorders such as eosinophilic esophagitis, eosinophilic gastroenteritis, acute and chronic eosinophilic pneumonia, and eosinophilic granulomatosis with polyangiitis. In infections, eosinophils are involved in protection not only from parasites but also from fungi, viruses, and bacteria. In solid cancers, local eosinophilic infiltration is variably associated with an improved or worsened prognosis, depending on the histotype. In hematologic neoplasms, eosinophilia can be the consequence of a dysregulated cytokine production or the result of mutations affecting the myeloid lineage.Recent experimental evidence was thoroughly reviewed, with findings which elicit a complex role for eosinophils, in a tight balance between host defense and tissue damage. Eventually, emerging evidence about eosinophils in COVID-19 infection was also discussed.
MeSH term(s)	Autoimmunity ; COVID-19 ; Churg-Strauss Syndrome ; Eosinophils ; Granulomatosis with Polyangiitis ; Humans ; Inflammation ; Rhinitis, Allergic ; SARS-CoV-2
Language	English
Publishing date	2021-05-25
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/5584_2021_640
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Article ; Online: Biomarkers and Diagnostic Testing for Renal Disease in Sjogren's Syndrome.

Ramponi, Giacomo / Folci, Marco / Badalamenti, Salvatore / Angelini, Claudio / Brunetta, Enrico

Frontiers in immunology

2020 Volume 11, Page(s) 562101

Abstract: Primary Sjogren's syndrome (pSS) is an autoimmune disorder in which lymphocytic infiltration leads to lacrimal and salivary glands dysfunction, which results in symptoms of dryness (xerophthalmia and xerostomia). Extraglandular features are common and ... ...

Abstract	Primary Sjogren's syndrome (pSS) is an autoimmune disorder in which lymphocytic infiltration leads to lacrimal and salivary glands dysfunction, which results in symptoms of dryness (xerophthalmia and xerostomia). Extraglandular features are common and may affect several organs. Renal involvement has long been known as one of the systemic complications of pSS. The most classical lesion observed in pSS is tubulointerstitial nephritis (TIN) and less frequently membranoproliferative glomerulonephritis (MPGN), which is related to cryoglobulinemia. In some cases, renal biopsy is necessary for the definitive diagnosis of kidney involvement. Patients may present with proximal renal tubular acidosis, distal renal tubular acidosis and chronic kidney disease. Response to treatment is usually favorable. However, occasionally severe and rarely lethal outcomes have been described. Recently, several case series and cross-sectional studies have been published which investigated the factors associated with renal involvement in pSS and the most accurate screening tests for early detection. The presence of xerophthalmia, anti-SSA and rheumatoid factor positivity, low C3 levels and other features have all shown either positive or inverse associations with the development of renal complications. Serum creatinine, alpha-1-microglobulin, cystatin-C have been evaluated as early detection biomarkers with variable accuracy. More advanced techniques may be necessary to confirm proximal and distal renal tubular acidosis, along with nephrogenic diabetes insipidus. The aim of the current paper is to summarize and critically examine these findings in order to provide updated guidance on serum biomarkers and further testing for kidney involvement in pSS.
MeSH term(s)	Alpha-Globulins/urine ; Autoimmunity ; Biomarkers/blood ; Biomarkers/urine ; Creatinine/blood ; Diagnostic Techniques and Procedures ; Glomerulonephritis, Membranoproliferative/complications ; Glomerulonephritis, Membranoproliferative/diagnosis ; Glomerulonephritis, Membranoproliferative/immunology ; Glomerulonephritis, Membranoproliferative/pathology ; Humans ; Kidney/pathology ; Nephritis, Interstitial/complications ; Nephritis, Interstitial/diagnosis ; Nephritis, Interstitial/immunology ; Nephritis, Interstitial/pathology ; Risk Factors ; Sjogren's Syndrome/complications
Chemical Substances	Alpha-Globulins ; Biomarkers ; alpha-1-microglobulin ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2020-09-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.562101
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Article: Learning Analytics Applied to Clinical Diagnostic Reasoning Using a Natural Language Processing-Based Virtual Patient Simulator: Case Study.

Furlan, Raffaello / Gatti, Mauro / Mene, Roberto / Shiffer, Dana / Marchiori, Chiara / Giaj Levra, Alessandro / Saturnino, Vincenzo / Brunetta, Enrico / Dipaola, Franca

JMIR medical education

2022 Volume 8, Issue 1, Page(s) e24372

Abstract: Background: Virtual patient simulators (VPSs) log all users' actions, thereby enabling the creation of a multidimensional representation of students' medical knowledge. This representation can be used to create metrics providing teachers with valuable ... ...

Abstract	Background: Virtual patient simulators (VPSs) log all users' actions, thereby enabling the creation of a multidimensional representation of students' medical knowledge. This representation can be used to create metrics providing teachers with valuable learning information. Objective: The aim of this study is to describe the metrics we developed to analyze the clinical diagnostic reasoning of medical students, provide examples of their application, and preliminarily validate these metrics on a class of undergraduate medical students. The metrics are computed from the data obtained through a novel VPS embedding natural language processing techniques. Methods: A total of 2 clinical case simulations (tests) were created to test our metrics. During each simulation, the students' step-by-step actions were logged into the program database for offline analysis. The students' performance was divided into seven dimensions: the identification of relevant information in the given clinical scenario, history taking, physical examination, medical test ordering, diagnostic hypothesis setting, binary analysis fulfillment, and final diagnosis setting. Sensitivity (percentage of relevant information found) and precision (percentage of correct actions performed) metrics were computed for each issue and combined into a harmonic mean (F Results: The mean overall scores were consistent between test 1 (mean 0.59, SD 0.05) and test 2 (mean 0.54, SD 0.12). For each student, the overall performance was achieved through a different contribution in collecting and analyzing information. Methodological scores highlighted discordances between the reference diagnostic pattern previously set by the teacher and the one pursued by the student. No significant correlation was found between the VPS scores and hematology examination scores. Conclusions: Different components of the students' diagnostic process may be disentangled and quantified by appropriate metrics applied to students' actions recorded while addressing a virtual case. Such an approach may help teachers provide students with individualized feedback aimed at filling competence drawbacks and methodological inconsistencies. There was no correlation between the hematology curricular examination score and any of the proposed scores as these scores address different aspects of students' medical knowledge.
Language	English
Publishing date	2022-03-03
Publishing country	Canada
Document type	Journal Article
ISSN	2369-3762
ISSN	2369-3762
DOI	10.2196/24372
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