6,735 results
Search Results
2. Anti-cytokine autoantibodies: mechanistic insights and disease associations.
- Author
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Cheng A and Holland SM
- Subjects
- Humans, Cytokines, Inflammation, Autoantibodies, Autoimmunity
- Abstract
Anti-cytokine autoantibodies (ACAAs) are increasingly recognized as modulating disease severity in infection, inflammation and autoimmunity. By reducing or augmenting cytokine signalling pathways or by altering the half-life of cytokines in the circulation, ACAAs can be either pathogenic or disease ameliorating. The origins of ACAAs remain unclear. Here, we focus on the most common ACAAs in the context of disease groups with similar characteristics. We review the emerging genetic and environmental factors that are thought to drive their production. We also describe how the profiling of ACAAs should be considered for the early diagnosis, active monitoring, treatment or sub-phenotyping of diseases. Finally, we discuss how understanding the biology of naturally occurring ACAAs can guide therapeutic strategies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
- Published
- 2024
- Full Text
- View/download PDF
3. Comment on the paper by Ebrahimi et al published in Journal of Oral Pathology & Medicine, 2011; 40: 281-285.
- Author
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Ogmundsdóttir HM and Holbrook WP
- Subjects
- Humans, Autoimmunity genetics, Genes, p53, Lichen Planus, Oral genetics
- Published
- 2011
- Full Text
- View/download PDF
4. Plenary papers on cutting edge autoimmunity. Proceedings of the Fifth International Congress on Autoimmunity. November 29-December 3, 2006. Sorrento, Italy.
- Subjects
- Animals, Humans, Autoimmune Diseases immunology, Autoimmunity
- Published
- 2007
5. Papers and abstracts from the 9th International Symposium on Antiphospholipid Antibodies. Tours, France, September 12-16, 2000.
- Subjects
- Animals, Humans, Antibodies, Antiphospholipid, Antiphospholipid Syndrome, Autoimmunity
- Published
- 2000
6. Papers presented at the 4th Summer School in Immunotoxicology. Aix-les-Bains, France, 18-20 October 1995.
- Subjects
- Animals, Humans, Allergy and Immunology, Autoimmunity, Toxicology
- Published
- 1997
7. A paperless autoimmunity laboratory: myth or reality?
- Author
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Lutteri L, Dierge L, Pesser M, Watrin P, and Cavalier E
- Subjects
- Antibodies, Antinuclear blood, Cells, Cultured, Critical Pathways standards, Humans, Image Processing, Computer-Assisted instrumentation, Image Processing, Computer-Assisted standards, Paper, Reference Standards, Sensitivity and Specificity, Antibodies, Antinuclear analysis, Autoimmunity, Automation, Laboratory instrumentation, Automation, Laboratory methods, Automation, Laboratory standards, Laboratories standards, Laboratories trends
- Abstract
Testing for antinuclear antibodies is the most frequently prescribed analysis for the diagnosis of rheumatic diseases. Indirect immunofluorescence remains the gold standard method for their detection despite the increasing use of alternative techniques. In order to standardize the manual microscopy reading, automated acquisition and interpretation systems have emerged. This publication enables us to present our method of interpretation and characterization of antinuclear antibodies based on a cascade of analyses and to share our everyday experience of the G Sight from Menarini. The positive/negative discrimination on Hep cells 2000 is correct in 85% of the cases. In most of the false negative results, it is a question of aspecific or low titers patterns, but a few cases of SSA speckled patterns of low titers demonstrated a probability index below 8. Regarding the pattern recognition, some types and mixed patterns are not properly recognized. Concerning the probability index correlated in some studies to final titer, the weak fluorescence of certain patterns and the random presence of artifacts that distort the index don't lead us to continue it in our daily practice. In conclusion, automated reading systems facilitate the reporting of results and traceability of patterns but still require the expertise of a laboratory technologist for positive/negative discrimination and for pattern recognition.
- Published
- 2016
- Full Text
- View/download PDF
8. Cytokine Storm in COVID-19—Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper
- Author
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Sonu Bhaskar, Akansha Sinha, Maciej Banach, Shikha Mittoo, Robert Weissert, Joseph S. Kass, Santhosh Rajagopal, Anupama R. Pai, and Shelby Kutty
- Subjects
COVID-19 ,cytokine storm ,immunological mechanisms ,autoimmunity ,neuroimmunology ,immunotherapies ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembolic diseases such as acute ischemic strokes caused by large vessel occlusion and myocardial infarction, encephalitis, acute kidney injury, and vasculitis (Kawasaki-like syndrome in children and renal vasculitis in adult). Understanding the pathogenesis of cytokine storm will help unravel not only risk factors for the condition but also therapeutic strategies to modulate the immune response and deliver improved outcomes in COVID-19 patients at high risk for severe disease. In this article, we present an overview of the cytokine storm and its implications in COVID-19 settings and identify potential pathways or biomarkers that could be targeted for therapy. Leveraging expert opinion, emerging evidence, and a case-based approach, this position paper provides critical insights on cytokine storm from both a prognostic and therapeutic standpoint.
- Published
- 2020
- Full Text
- View/download PDF
9. Immune modulation via T regulatory cell enhancement: Disease‐modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases—An EAACI position paper of the Task Force on Immunopharmacology (TIPCO).
- Author
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Roth‐Walter, Franziska, Adcock, Ian M., Benito‐Villalvilla, Cristina, Bianchini, Rodolfo, Bjermer, Leif, Boyman, Onur, Caramori, Gaetano, Cari, Luigi, Fan Chung, Kian, Diamant, Zuzana, Eguiluz‐Gracia, Ibon, Knol, Edward F., Kolios, Antonios, Levi‐Schaffer, Francesca, Nocentini, Giuseppe, Palomares, Oscar, Redegeld, Frank, Van Esch, Betty, and Stellato, Cristiana
- Subjects
- *
SUPPRESSOR cells , *IMMUNOREGULATION , *ALLERGIES , *TASK forces , *AUTOIMMUNITY - Abstract
Therapeutic advances using targeted biologicals and small‐molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune, and inflammatory diseases particularly for some patients with severe, treatment‐resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements, not all severe forms of chronic inflammatory and autoimmune diseases are successfully targeted, and current treatment options, besides allergen immunotherapy for selected allergic diseases, fail to change the disease course. T cell–based therapies aim to cure diseases through the selective induction of appropriate immune responses following the delivery of engineered, specific cytotoxic, or regulatory T cells (Tregs). Adoptive cell therapies (ACT) with genetically engineered T cells have revolutionized the oncology field, bringing curative treatment for leukemia and lymphoma, while therapies exploiting the suppressive functions of Tregs have been developed in nononcological settings, such as in transplantation and autoimmune diseases. ACT with Tregs are also being considered in nononcological settings such as cardiovascular disease, obesity, and chronic inflammatory disorders. After describing the general features of T cell–based approaches and current applications in autoimmune diseases, this position paper reviews the experimental models testing or supporting T cell–based approaches, especially Treg‐based approaches, in severe IgE‐mediated responses and chronic respiratory airway diseases, such as severe asthma and COPD. Along with an assessment of challenges and unmet needs facing the application of ACT in these settings, this article underscores the potential of ACT to offer curative options for patients with severe or treatment‐resistant forms of these immune‐driven disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
10. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?
- Author
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Akdis CA
- Subjects
- Animals, Chronic Disease epidemiology, Dermatitis, Atopic epidemiology, Humans, Rhinitis, Allergic epidemiology, Autoimmune Diseases epidemiology, Autoimmunity, Hypersensitivity epidemiology
- Abstract
There has been a steep increase in allergic and autoimmune diseases, reaching epidemic proportions and now affecting more than one billion people worldwide. These diseases are more common in industrialized countries, and their prevalence continues to rise in developing countries in parallel to urbanization and industrialization. Intact skin and mucosal barriers are crucial for the maintenance of tissue homeostasis as they protect host tissues from infections, environmental toxins, pollutants and allergens. A defective epithelial barrier has been demonstrated in allergic and autoimmune conditions such as asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, coeliac disease and inflammatory bowel disease. In addition, leakiness of the gut epithelium is also implicated in systemic autoimmune and metabolic conditions such as diabetes, obesity, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and autoimmune hepatitis. Finally, distant inflammatory responses due to a 'leaky gut' and microbiome changes are suspected in Alzheimer disease, Parkinson disease, chronic depression and autism spectrum disorders. This article introduces an extended 'epithelial barrier hypothesis', which proposes that the increase in epithelial barrier-damaging agents linked to industrialization, urbanization and modern life underlies the rise in allergic, autoimmune and other chronic conditions. Furthermore, it discusses how the immune responses to dysbiotic microbiota that cross the damaged barrier may be involved in the development of these diseases., (© 2021. Springer Nature Limited.)
- Published
- 2021
- Full Text
- View/download PDF
11. The Autoimmunity of the EU's Deadly B/ordering Regime; Overcoming its Paradoxical Paper, Iron and Camp Borders.
- Author
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van Houtum, Henk and Bueno Lacy, Rodrigo
- Subjects
- *
AUTOIMMUNITY , *UNDOCUMENTED immigrants , *CONCENTRATION camps , *IRON , *CAMPS - Abstract
In this article we argue that the EU suffers from autoimmunity: a self-harming protection strategy. Drawing on Derrida's political understanding of autoimmunity, we contend that the root of this malfunction lies in the EU's own b/ordering and othering policies, which are intended to immunise the foundational ethos of the EU. For this purpose, we dissect the EU border regime into three linked b/ordering mechanisms: the pre-borders of paper documents that regulate from afar the mobility of the people from visa-obliged countries; the actual land borders often consisting of iron gates and fences regulating mobility on the spot; and the post-border in the form of waiting/detention camps that segregate and enclose the undocumented migrants after entry. We make clear how this discriminatory b/ordering and othering regime has led to a recurrent drawing of ever less porous, inhumane and deadlier borders. Such thanatopolitics finds itself at odds with the humanist values that the EU is supposed to uphold, particularly cross-border solidarity, openness, non-discrimination and human rights. We argue that the EU b/ordering regime has turned fear of the non-EUropean into an increasingly unquestioned – even 'commonsensical' – anxiety that has become politically profitable to exploit by extreme nationalistic and EUrosceptic parties. The core of the EU's autoimmunity that we want to expose lies within this irony: in its attempt to protect what it considers meaningful, the EU has unleashed an autoimmune disorder that has turned the EU into its own most formidable threat. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
12. Immune modulation via T regulatory cell enhancement: disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases - An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)
- Author
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Antonios G.A. Kolios, Ian M. Adcock, Betty C.A.M. van Esch, Onur Boyman, Zuzana Diamant, Cristina Benito-Villalvilla, Francesca Levi-Schaffer, Frank A. Redegeld, Giuseppe Nocentini, Kian Fan Chung, Leif Bjermer, Luigi Cari, Rodolfo Bianchini, Gaetano Caramori, Ibon Eguiluz-Gracia, Oscar Palomares, Cristiana Stellato, Edward F. Knol, Franziska Roth-Walter, Afd Pharmacology, Pharmacology, University of Zurich, and Stellato, Cristiana
- Subjects
Adoptive cell transfer ,Disease ,medicine.disease_cause ,T-Lymphocytes, Regulatory ,FOOD ALLERGY ,adoptive cell therapies ,Autoimmunity ,CONFERS PROTECTION ,0302 clinical medicine ,allergy ,autoimmunity ,CAR-Treg cells ,immunoregulation ,Immunology and Allergy ,LYMPHOCYTE-ACTIVATION ,EXPERIMENTAL COLITIS ,10177 Dermatology Clinic ,MOUSE MODEL ,CAR‐ ,medicine.anatomical_structure ,1107 Immunology ,2723 Immunology and Allergy ,Allergen immunotherapy ,T cell ,Immunology ,DNA METHYLTRANSFERASE ,610 Medicine & health ,Autoimmune Diseases ,03 medical and health sciences ,Immune system ,medicine ,Hypersensitivity ,Humans ,ADOPTIVE TRANSFER ,2403 Immunology ,TRANSCRIPTION FACTOR FOXP3 ,business.industry ,Immunopharmacology ,Asthma ,Transplantation ,ATTENUATES AIRWAY INFLAMMATION ,ORAL TOLERANCE ,030228 respiratory system ,10033 Clinic for Immunology ,business ,Treg cells ,030215 immunology - Abstract
Therapeutic advances using targeted biologicals and small-molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune, and inflammatory diseases particularly for some patients with severe, treatment-resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements, not all severe forms of chronic inflammatory and autoimmune diseases are successfully targeted, and current treatment options, besides allergen immunotherapy for selected allergic diseases, fail to change the disease course. T cell-based therapies aim to cure diseases through the selective induction of appropriate immune responses following the delivery of engineered, specific cytotoxic, or regulatory T cells (Tregs). Adoptive cell therapies (ACT) with genetically engineered T cells have revolutionized the oncology field, bringing curative treatment for leukemia and lymphoma, while therapies exploiting the suppressive functions of Tregs have been developed in nononcological settings, such as in transplantation and autoimmune diseases. ACT with Tregs are also being considered in nononcological settings such as cardiovascular disease, obesity, and chronic inflammatory disorders. After describing the general features of T cell-based approaches and current applications in autoimmune diseases, this position paper reviews the experimental models testing or supporting T cell-based approaches, especially Treg-based approaches, in severe IgE-mediated responses and chronic respiratory airway diseases, such as severe asthma and COPD. Along with an assessment of challenges and unmet needs facing the application of ACT in these settings, this article underscores the potential of ACT to offer curative options for patients with severe or treatment-resistant forms of these immune-driven disorders.
- Published
- 2021
13. Regulatory T cells and immunoglobulin E: A new therapeutic link for autoimmunity?
- Author
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Palomares O, Elewaut D, Irving PM, Jaumont X, and Tassinari P
- Subjects
- Humans, T-Lymphocytes, Regulatory, Immunoglobulin E, Immune Tolerance, Autoimmunity, Autoimmune Diseases
- Abstract
Autoimmune diseases have a prevalence of approximately 7 to 9% and are classified as either organ-specific diseases, including type I diabetes, multiple sclerosis, inflammatory bowel disease and myasthenia gravis, or systemic diseases, including systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome. While many advancements have been made in understanding of the mechanisms of autoimmune disease, including the nature of self-tolerance and its breakdown, there remain unmet needs in terms of effective and highly targeted treatments. T regulatory cells (Tregs) are key mediators of peripheral tolerance and are implicated in many autoimmune diseases, either as a result of reduced numbers or altered function. Tregs may be broadly divided into those generated in the thymus (tTregs) and those generated in the periphery (pTregs). Tregs target many different immune cell subsets and tissues to suppress excessive inflammation and to support tissue repair and homeostasis: there is a fine balance between Treg cell stability and the plasticity that is required to adjust Tregs' regulatory purposes to particular immune responses. The central role of immunoglobulin E (IgE) in allergic disease is well recognized, and it is becoming increasingly apparent that this immunoglobulin also has a wider role encompassing other diseases including autoimmune disease. Anti-IgE treatment restores the capacity of plasmacytoid dendritic cells (pDCs) impaired by IgE- high-affinity IgE receptor (FcεR1) cross-linking to induce Tregs in vitro in atopic patients. The finding that anti-IgE therapy restores Treg cell homeostasis, and that this mechanism is associated with clinical improvement in asthma and chronic spontaneous urticaria suggests that anti-IgE therapy may also have a potential role in the treatment of autoimmune diseases in which Tregs are involved., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
14. Researchers from Guangzhou Medical University Detail Findings in Autoimmunity (Paper Rnf157 Attenuates Cd4+t Cell-mediated Autoimmune Response By Promoting Hdac1 Ubiquitination and Degradation).
- Abstract
Keywords: Guangzhou; People's Republic of China; Asia; Autoimmunity; Cell Differentiation; Immunology; Peptides and Proteins; Proteins; Ubiquitins EN Guangzhou People's Republic of China Asia Autoimmunity Cell Differentiation Immunology Peptides and Proteins Proteins Ubiquitins 1318 1318 1 08/21/23 20230825 NES 230825 2023 AUG 25 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Weekly -- A new study on Immunology - Autoimmunity is now available. Guangzhou, People's Republic of China, Asia, Autoimmunity, Cell Differentiation, Immunology, Peptides and Proteins, Proteins, Ubiquitins. [Extracted from the article]
- Published
- 2023
15. Marking the 50th anniversary of a seminal paper in rheumatology: did Baruj Benacerraf and Hugh McDevitt get it right?
- Author
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Rosenbaum, James Todd, Gill, Tejpal, Martin, Tammy M., Friedman, Marcia, and Thompson, Reid
- Published
- 2022
- Full Text
- View/download PDF
16. Integrating quality assurance in autoimmunity: the changing face of the automated ANA IIF test.
- Author
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Van Hoovels L, Bossuyt X, Manfredi M, Grossi V, Benucci M, Van Den Bremt S, De Baere H, Franceschi D, Tosi E, Meoni M, Bizzaro N, and Infantino M
- Subjects
- Diagnostic Tests, Routine, Fluorescent Antibody Technique, Indirect, Humans, Quality Control, Antibodies, Antinuclear, Autoimmunity
- Abstract
Objectives: Currently available computer-aided diagnosis (CAD) systems for the detection of anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) assay enable a standardized measurement of system-specific fluorescent intensity (FI) measures. We aimed to evaluate an internal quality control (iQC) program that controls the total ANA IIF process in routine practice., Methods: In addition to the kit iQC materials, supplemental quality indicators were integrated in a total quality assurance (QA) program: patient-derived iQC's samples (negative, 1/160 fine speckled and 1/160 homogeneous), median sample FI per run and percentage of ANA IIF positive samples per run. Analytical rejection criteria were based on the imprecision of the positivity index (PI) measure of the Zenit PRO system (Menarini). Clinical rejection criteria were based on changes in FI that correspond to a change in ANA IIF titer of ≥2. To evaluate the QA program, different artificial errors were introduced during the ANA IIF process. After every run, quality indicators were evaluated and compared to the pre-set target values., Results: Rescanning the ANA IIF slides five times, using an old conjugate and a needle obstruction resulted in analytically and even clinically relevant errors in ANA IIF results. All errors were correctly detected by the different defined quality indicators. Traditional Westgard rules, including analytically (and clinically) defined rejection limits were useful in monitoring quality indicators., Conclusions: The integration of a total process iQC program in CAD systems, based on the specific FI measurands and performance criteria of the system, adds value to QA., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)
- Published
- 2021
- Full Text
- View/download PDF
17. Imploding Singularities: For a Critique of Autoimmunity as Political Future1My thanks to the referee who suggested the title for this paper in order to describe the interventionist note on which this essay ends. The previous title, as the referee suggested, had a more fatalistic tone in the subheading: “Autoimmunity as Political Future”.
- Author
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Osuri, Goldie
- Subjects
- *
ORIENTALISM , *IMPERIALISM , *NATIONALISM , *AUTOIMMUNITY , *DECONSTRUCTION , *POLITICAL science - Abstract
This paper traces the resilience of Orientalist representations in contemporary political and popular cultural constructions of space and time. Derrida's deconstruction of universalist notions of space and time enables a challenge to these mechanisms. However, our contemporary political era in the context of the war between terrorisms is marked by an implosion of the Enlightenment concept of universal space and time and the attempt to negate multiple spacetimes. In this sense, Derrida's concept of autoimmunity appears to be a necessary theoretical tool in reading our political future in relation to wars between state and other terrorisms. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
18. Cytokine Storm in COVID-19—Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper.
- Author
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Bhaskar, Sonu, Sinha, Akansha, Banach, Maciej, Mittoo, Shikha, Weissert, Robert, Kass, Joseph S., Rajagopal, Santhosh, Pai, Anupama R., and Kutty, Shelby
- Subjects
CYTOKINE release syndrome ,COVID-19 ,SARS-CoV-2 ,ADULT respiratory distress syndrome ,PATHOLOGY - Abstract
Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembolic diseases such as acute ischemic strokes caused by large vessel occlusion and myocardial infarction, encephalitis, acute kidney injury, and vasculitis (Kawasaki-like syndrome in children and renal vasculitis in adult). Understanding the pathogenesis of cytokine storm will help unravel not only risk factors for the condition but also therapeutic strategies to modulate the immune response and deliver improved outcomes in COVID-19 patients at high risk for severe disease. In this article, we present an overview of the cytokine storm and its implications in COVID-19 settings and identify potential pathways or biomarkers that could be targeted for therapy. Leveraging expert opinion, emerging evidence, and a case-based approach, this position paper provides critical insights on cytokine storm from both a prognostic and therapeutic standpoint. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
19. Anti-neutrophil cytoplasmic antibodies (ANCA): Antigen interactions and downstream effects.
- Author
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Sundqvist M, Gibson KM, Bowers SM, Niemietz I, and Brown KL
- Subjects
- Animals, Autoimmune Diseases etiology, Autoimmune Diseases metabolism, Cytoplasmic Granules immunology, Cytoplasmic Granules metabolism, Disease Susceptibility, Gene Expression Regulation, Humans, Neutrophil Activation immunology, Neutrophils metabolism, Peroxidase metabolism, Protein Transport, Antibodies, Antineutrophil Cytoplasmic immunology, Antigens immunology, Autoantibodies immunology, Autoimmunity, Neutrophils immunology
- Abstract
Neutrophils are the most abundant leukocytes in circulation and are key "first responders" in the immune response to infectious and non-infectious stimuli. Unlike other immune cells, neutrophils can mount a robust response (including a change in surface markers and the production of extracellular traps and reactive oxygen species) just minutes after sensing a disturbance. It has been speculated that, in some individuals, the activation of neutrophils inadvertently leads to the generation of anti-neutrophil cytoplasmic autoantibodies (ANCA) against particular neutrophil proteins (antigens) such as myeloperoxidase (MPO) and proteinase 3 (PR3). In these individuals, continuous ANCA-antigen interactions are thought to drive persistent activation of neutrophils, chronic immune activation, and disease, most notably, small vessel vasculitis. There are significant gaps however in our understanding of the underlying mechanisms and even the pathogenicity of ANCA given that vasculitis can develop in the absence of ANCA, and that ANCA have been found in circulation in other conditions with no apparent contribution to disease. These gaps are particularly evident in the context of human studies. Herein, we review knowledge on neutrophil-derived ANCA antigens PR3 and MPO, ANCA generation, and ANCA-antigen interaction(s) that may promote immune activation and disease., (©2020 Society for Leukocyte Biology.)
- Published
- 2020
- Full Text
- View/download PDF
20. IMPORTANT RESEARCH QUESTIONS IN ALLERGY AND RELATED DISEASES: NONALLERGIC RHINITIS: A GA2LEN PAPER
- Author
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J, Bousquet, W, Fokkens, P, Burney, S R, Durham, C, Bachert, C A, Akdis, G W, Canonica, S-E, Dahlen, T, Zuberbier, T, Bieber, S, Bonini, P J, Bousquet, J L, Brozek, L-O, Cardell, R, Crameri, A, Custovic, P, Demoly, R G, van Wijk, M, Gjomarkaj, C, Holland, P, Howarth, M, Humbert, S L, Johnston, F, Kauffmann, M L, Kowalski, B, Lambrecht, S, Lehmann, B, Leynaert, K, Lodrup-Carlsen, J, Mullol, B, Niggemann, E, Nizankowska-Mogilnicka, N, Papadopoulos, G, Passalacqua, H J, Schünemann, H-U, Simon, A, Todo-Bom, E, Toskala, R, Valenta, M, Wickman, J P, Zock, Bousquet, J, Fokkens, W, Burney, P, Durham, Sr, Bachert, C, Akdis, Ca, Canonica, Gw, Dahlen, Se, Zuberbier, T, Bieber, T, Bonini, Sergio, Bousquet, Pj, Brozek, Jl, Cardell, Lo, Crameri, R, Custovic, A, Demoly, P, VAN WIJK, Rg, Gjomarkaj, M, Holland, C, Howarth, P, Humbert, M, Johnston, Sl, Kauffmann, F, Kowalski, Ml, Lambrecht, B, Lehmann, S, Leynaert, B, LODRUP CARLSEN, K, Mullol, J, Niggemann, B, NIZANKOWSKA MOGILNICKA, E, Papadopoulos, N, Passalacqua, G, Schünemann, Hj, Simon, Hu, TODO BOM, A, Toskala, E, Valenta, R, Wickman, M, Zock, Jp, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Internal Medicine, Pulmonary Medicine, and University of Zurich
- Subjects
Proteomics ,2403 Immunology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Anti-Inflammatory Agents, Non-Steroidal ,Disease Management ,Autoimmunity ,610 Medicine & health ,Comorbidity ,Dendritic Cells ,Genomics ,Immunoglobulin E ,T-Lymphocytes, Regulatory ,Immunity, Innate ,Cohort Studies ,Europe ,Phenotype ,10183 Swiss Institute of Allergy and Asthma Research ,Surveys and Questionnaires ,Prevalence ,2723 Immunology and Allergy ,Humans ,Sinusitis ,ComputingMilieux_MISCELLANEOUS ,Rhinitis - Abstract
Nonallergic rhinitis (NAR) can be defined as a chronic nasal inflammation which is not caused by systemic IgE-dependent mechanisms. It is common and probably affects far more than 200 million people worldwide. Both children and adults are affected. However, its exact prevalence is unknown and its phenotypes need to be evaluated using appropriate methods to better understand its pathophysiology, diagnosis and management. It is important to differentiate between infectious rhinitis, allergic/NAR and chronic rhinosinusitis, as management differs for each of these cases. Characterization of the phenotype, mechanisms and management of NAR represents one of the major unmet needs in allergic and nonallergic diseases. Studies on children and adults are required in order to appreciate the prevalence, phenotype, severity and co-morbidities of NAR. These studies should compare allergic and NAR and consider different age group populations including elderly subjects. Mechanistic studies should be carried out to better understand the disease(s) and risk factors and to guide towards an improved diagnosis and therapy. These studies need to take the heterogeneity of NAR into account. It is likely that neuronal mechanisms, T cells, innate immunity and possibly auto-immune responses all play a role in NAR and may also contribute to the symptoms of allergic rhinitis.
- Published
- 2008
21. Unraveling the enigma of long COVID: novel aspects in pathogenesis, diagnosis, and treatment protocols.
- Author
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Baig, Abdul Mannan, Rosko, Sandy, Jaeger, Beate, Gerlach, Joachim, and Rausch, Hans
- Subjects
POST-acute COVID-19 syndrome ,THERAPEUTICS ,VIRAL proteins ,HOSPITAL patients ,VIRAL replication - Abstract
Long COVID, now unmistakably identified as a syndromic entity encompassing a complex spectrum of symptoms, demands immediate resolution of its elusive pathogenic underpinnings. The intricate interplay of diverse factors presents a complex puzzle, difficult to resolve, and thus poses a substantial challenge. As instances of long COVID manifest by repeated infections of SARS-CoV-2 and genetic predisposition, a detailed understanding in this regard is needed. This endeavor is a comprehensive exploration and analysis of the cascading pathogenetic events driven by viral persistence and replication. Beyond its morbidity, long COVID, more disabling than fatal, exacts one of the most substantial tolls on public health in contemporary times, with the potential to cripple national economies. The paper introduces a unified theory of long COVID, detailing a novel pathophysiological framework that interlinks persistent SARS-CoV-2 infection, autoimmunity, and systemic vascular pathology. We posit a model where viral reservoirs, immune dysregulation, and genetic predispositions converge to perpetuate disease. It challenges prevailing hypotheses with new evidence, suggesting innovative diagnostic and therapeutic approaches. The paper aims to shift the paradigm in long COVID research by providing an integrative perspective that encapsulates the multifaceted nature of the condition. We explain the immunological mechanisms, hypercoagulability states, and viral reservoirs in the skull that feed NeuroCOVID in patients with long COVID. Also, this study hints toward a patient approach and how to prioritize treatment sequences in long COVID patients in hospitals and clinics. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
22. RAPID PAPER.
- Author
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Williams, Yvonne, Lynch, Sara, McCann, Shaun, Smith, Owen, Feighery, Conleth, and Whelan, Alex
- Subjects
- *
THROMBOPENIC purpura , *GENETIC polymorphisms , *IMMUNOGLOBULIN G , *BLOOD platelets , *AUTOIMMUNITY - Abstract
FcγRIIA, a low affinity receptor for IgG, is a polymorphic molecule: FcγRIIA-HH131, FcγRIIA-HR131 and FcγRIIA-RR131. This polymorphism influences the efficiency of the receptor to bind with IgG2. Recent reports on altered distribution amongst individuals with heparin-induced thrombocytopenia (HIT) prompted us to examine the FcγRIIA polymorphism in a cohort of patients with refractory idiopathic (immune) thrombocytopenic purpura (ITP), in whom severe disease had required them to undergo splenectomy. 29 post splenectomy ITP individuals and 61 normal controls were investigated. Polymerase chain reaction (PCR) and a Southern blotting technique were used to determine the FcγRII polymorphism. Although the distribution of the allotypes of FcγRIIA in the control population was similar to that found in other European studies of Caucasian populations (15 (25%) HH131; 35 (57%) HR131; 11(18%) RR131), the patient group was skewed towards the RR131 allotype which has least efficiency for IgG2 binding (3 (10%) HH131; 12 (42%) HR131; 14 (48%) RR131; P < 0.005). These findings suggest that FcγRIIA polymorphisms may be implicated in the pathophysiology of ITP or may be responsible for modulating the immune response in this heterogenous autoimmune disease. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
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23. A meta-analysis of structural MRI studies of the brain in systemic lupus erythematosus (SLE).
- Author
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Cox, Jennifer G., de Groot, Marius, Cole, James H., Williams, Steven C. R., and Kempton, Matthew J.
- Subjects
SYSTEMIC lupus erythematosus ,CORPUS callosum ,GRAY matter (Nerve tissue) ,AUTOIMMUNE diseases ,WHITE matter (Nerve tissue) - Abstract
A comprehensive search of published literature in brain volumetry was conducted in three autoimmune diseases — systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ulcerative colitis (UC) — with the intention of performing a meta-analysis of published data. Due to the lack of data in RA and UC, the reported meta-analysis was limited to SLE. The MEDLINE database was searched for studies from 1988 to March 2022. A total of 175 papers met the initial inclusion criteria, and 16 were included in a random-effects meta-analysis. The reduction in the number of papers included in the final analysis is primarily due to the lack of overlap in measured and reported brain regions. A significantly lower volume was seen in patients with SLE in the hippocampus, corpus callosum, and total gray matter volume measurements as compared to age- and sex-matched controls. There were not enough studies to perform a meta-analysis for RA and UC; instead, we include a summary of published volumetric studies. The meta-analyses revealed structural brain abnormalities in patients with SLE, suggesting that lower global brain volumes are associated with disease status. This volumetric difference was seen in both the hippocampus and corpus callosum and total gray matter volume measurements. These results indicate both gray and white matter involvements in SLE and suggest there may be both localized and global reductions in brain volume. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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24. Animal Models of Human Disease.
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Lange, Sigrun and Inal, Jameel M.
- Subjects
TRANSLATIONAL research ,ENDOCRINE diseases ,MITOCHONDRIAL pathology ,DEGENERATION (Pathology) - Abstract
The use of animal models of human disease is critical for furthering our understanding of disease mechanisms, for the discovery of novel targets for treatment, and for translational research. This Special Topic entitled "Animal Models of Human Disease" aimed to collect state-of-the-art primary research studies and review articles from international experts and leading groups using animal models to study human diseases. Submissions were welcomed on a wide range of animal models and pathologies, including infectious disease, acute injury, regeneration, cancer, autoimmunity, degenerative and chronic disease. Seven participating MDPI journals supported the Special Topic, namely: Biomedicines, Cells, Current Issues in Molecular Biology, Diagnostics, Genes, the International Journal of Molecular Sciences, and the International Journal of Translational Medicine. In total, 46 papers were published in this Special Topic, with 37 full length original research papers, 2 research communications and 7 reviews. These contributions cover a wide range of clinically relevant, translatable, and comparative animal models, as well as furthering understanding of fundamental sciences, covering topics on physiological processes, on degenerative, inflammatory, infectious, autoimmune, neurological, metabolic, heamatological, hormonal and mitochondrial disorders, developmental processes and diseases, cardiology, cancer, trauma, stress, and ageing. [ABSTRACT FROM AUTHOR]
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- 2023
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25. The autoimmune response induced by α-synuclein peptides drives neuronal cell death and glial cell activation.
- Author
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Choe YH, Jo MG, Kim BG, Lee S, Lee B, Kim SH, Seong H, Yoo WS, Kim M, Lee DK, Kim SJ, Yun SP, and Kim M
- Subjects
- Animals, Mice, Neuroglia immunology, Neuroglia metabolism, Neuroglia drug effects, Parkinson Disease immunology, Parkinson Disease pathology, Parkinson Disease metabolism, Mice, Inbred C57BL, Humans, Lymphocyte Activation immunology, Lymphocyte Activation drug effects, Peptides immunology, Cells, Cultured, Female, T-Lymphocytes, Regulatory immunology, alpha-Synuclein immunology, alpha-Synuclein metabolism, Autoimmunity, Cell Death drug effects, Neurons immunology, Neurons metabolism, Neurons pathology
- Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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26. Engineering antigen-presenting cells for immunotherapy of autoimmunity.
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Smith CT, Wang Z, and Lewis JS
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- Humans, Animals, Antigen-Presenting Cells immunology, Autoimmune Diseases immunology, Autoimmune Diseases therapy, Immunotherapy methods, Autoimmunity immunology
- Abstract
Autoimmune diseases are burdensome conditions that affect a significant fraction of the global population. The hallmark of autoimmune disease is a host's immune system being licensed to attack its tissues based on specific antigens. There are no cures for autoimmune diseases. The current clinical standard for treating autoimmune diseases is the administration of immunosuppressants, which weaken the immune system and reduce auto-inflammatory responses. However, people living with autoimmune diseases are subject to toxicity, fail to mount a sufficient immune response to protect against pathogens, and are more likely to develop infections. Therefore, there is a concerted effort to develop more effective means of targeting immunomodulatory therapies to antigen-presenting cells, which are involved in modulating the immune responses to specific antigens. In this review, we highlight approaches that are currently in development to target antigen-presenting cells and improve therapeutic outcomes in autoimmune diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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27. A novel mechanism of idiopathic orthostatic hypotension and hypocatecholaminemia due to autoimmunity against aromatic l-Amino acid decarboxylase.
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Uenishi E, Seino Y, Nakashima A, Kato K, Kato M, Nagasaki H, Ishikawa K, Izumoto T, Yamamoto M, Takahashi Y, Sugimura Y, Oiso Y, and Tsunekawa S
- Subjects
- Female, Humans, Middle Aged, Autoantibodies blood, Autoantibodies immunology, Catecholamines, Dopamine metabolism, Serotonin metabolism, Aromatic-L-Amino-Acid Decarboxylases deficiency, Autoimmunity, Hypotension, Orthostatic etiology, Hypotension, Orthostatic physiopathology
- Abstract
Orthostatic hypotension (OH) is a common condition. Many potential etiologies of OH have been identified, but in clinical practice the underlying cause of OH is often unknown. In the present study, we identified a novel and extraordinary etiology of OH. We describe a first case of acquired severe OH with syncope, and the female patient had extremely low levels of catecholamines and serotonin in plasma, urine and cerebrospinal fluid (CSF). Her clinical and biochemical evidence showed a deficiency of the enzyme aromatic l-amino acid decarboxylase (AADC), which converts l-DOPA to dopamine, and 5-hydroxytryptophan to serotonin, respectively. The consequence of pharmacologic stimulation of catecholaminergic nerves and radionuclide examination revealed her catecholaminergic nerves denervation. Moreover, we found that the patient's serum showed presence of autoantibodies against AADC, and that isolated peripheral blood mononuclear cells (PBMCs) from the patient showed cytokine-induced toxicity against AADC. These observations suggest that her autoimmunity against AADC is highly likely to cause toxicity to adrenal medulla and catecholaminergic nerves which contain AADC, resulting in hypocatecholaminemia and severe OH. Administration of vitamin B6, an essential cofactor of AADC, enhanced her residual AADC activity and drastically improved her symptoms. Our data thus provide a new insight into pathogenesis and pathophysiology of OH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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28. Circulating Autoantibody Profiling Identifies LIMS1 as a Potential Target for Pathogenic Autoimmunity in pathologic Myopia.
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Qi J, Li H, Du Y, Liu Y, He W, Meng J, Wei L, Zhang K, Lu Y, and Zhu X
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- Humans, Male, Female, Immunoglobulin G immunology, Immunoglobulin G blood, Middle Aged, Myopia, Degenerative immunology, Myopia immunology, Adult, Autoantibodies immunology, Autoantibodies blood, Retinal Pigment Epithelium pathology, Retinal Pigment Epithelium metabolism, Autoimmunity
- Abstract
High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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29. Idiopathic and connective tissue disease-associated pulmonary arterial hypertension (PAH): Similarities, differences and the role of autoimmunity.
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Favoino E, Prete M, Liakouli V, Leone P, Sisto A, Navarini L, Vomero M, Ciccia F, Ruscitti P, Racanelli V, Giacomelli R, and Perosa F
- Subjects
- Humans, Pulmonary Arterial Hypertension immunology, Pulmonary Arterial Hypertension etiology, Pulmonary Arterial Hypertension physiopathology, Hypertension, Pulmonary immunology, Hypertension, Pulmonary etiology, Hypertension, Pulmonary physiopathology, Familial Primary Pulmonary Hypertension physiopathology, Familial Primary Pulmonary Hypertension immunology, Connective Tissue Diseases immunology, Connective Tissue Diseases complications, Autoimmunity
- Abstract
Pre-capillary pulmonary arterial hypertension (PAH) is hemodynamically characterized by a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg, pulmonary capillary wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) > 2. PAH is classified in six clinical subgroups, including idiopathic PAH (IPAH) and PAH associated to connective tissue diseases (CTD-PAH), that will be the main object of this review. The aim is to compare these two PAH subgroups in terms of epidemiology, histological and pathogenic findings in an attempt to define disease-specific features, including autoimmunity, that may explain the heterogeneity of response to therapy between IPAH and CTD-PAH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2024
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30. From inflammation to renal fibrosis: A one-way road in autoimmunity?
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Roccatello D, Lan HY, Sciascia S, Sethi S, Fornoni A, and Glassock R
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- Humans, Animals, Kidney pathology, Kidney immunology, Kidney Diseases immunology, Kidney Diseases pathology, Fibrosis, Autoimmunity immunology, Inflammation immunology, Inflammation pathology
- Abstract
Renal fibrosis is now recognized as a main determinant of renal pathology to include chronic kidney disease. Deposition of pathological matrix in the walls of glomerular capillaries, the interstitial space, and around arterioles predicts and contributes to the functional demise of the nephron and its surrounding vasculature. The recent identification of the major cell populations of fibroblast precursors in the kidney interstitium such as pericytes and tissue-resident mesenchymal stem cells, or bone-marrow-derived macrophages, and in the glomerulus such as podocytes, parietal epithelial and mesangial cells, has enabled the study of the fibrogenic process thought the lens of involved immunological pathways. Besides, a growing body of evidence is supporting the role of the lymphatic system in modulating the immunological response potentially leading to inflammation and ultimately renal damage. These notions have moved our understanding of renal fibrosis to be recognized as a clinical entity and new main player in autoimmunity, impacting directly the management of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2024
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31. Herpes vaccine, splenectomy, and thymectomy associated with autoimmune diseases and the kaleidoscope of autoimmunity.
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Lucas Hernández A, Shovman O, Langevitz P, and Shoenfeld Y
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- Humans, Autoimmune Diseases immunology, Splenectomy, Thymectomy, Autoimmunity
- Abstract
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2024
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32. Editorial: Myeloid-derived suppressor cells in health and diseases: harnessing their roles in the development of new immunotherapy approaches.
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Tomić, Sergej, Shengjun Wang, and Čolić, Miodrag
- Subjects
MYELOID-derived suppressor cells ,AUTOIMMUNE diseases ,HTLV - Abstract
This document is an editorial published in the journal Frontiers in Immunology. It discusses the role of myeloid-derived suppressor cells (MDSCs) in various health conditions and diseases, including cancer, autoimmunity, pregnancy, neonates, and aging. The editorial highlights the complexity of MDSCs and their potential as targets for immunotherapy. It also presents five research papers that provide insights into the multifaceted roles of MDSCs in oncogenesis, maternal-fetal interface, and aging, contributing to a better understanding of MDSCs biology and the development of more effective immunotherapeutic approaches. [Extracted from the article]
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- 2024
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33. PPARs at the crossroads of T cell differentiation and type 1 diabetes.
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Riaz, Farooq, Ping Wei, and Fan Pan
- Subjects
TYPE 1 diabetes ,T cell differentiation ,PEROXISOME proliferator-activated receptors ,T helper cells ,PANCREATIC beta cells - Abstract
T-cell-mediated autoimmune type 1 diabetes (T1D) is characterized by the immune-mediated destruction of pancreatic beta cells (b-cells). The increasing prevalence of T1D poses significant challenges to the healthcare system, particularly in countries with struggling economies. This review paper highlights the multifaceted roles of Peroxisome Proliferator-Activated Receptors (PPARs) in the context of T1D, shedding light on their potential as regulators of immune responses and b-cell biology. Recent research has elucidated the intricate interplay between CD4+ T cell subsets, such as Tregs and Th17, in developing autoimmune diseases like T1D. Th17 cells drive inflammation, while Tregs exert immunosuppressive functions, highlighting the delicate balance crucial for immune homeostasis. Immunotherapy has shown promise in reinstating self-tolerance and restricting the destruction of autoimmune responses, but further investigations are required to refine these therapeutic strategies. Intriguingly, PPARs, initially recognized for their role in lipid metabolism, have emerged as potent modulators of inflammation in autoimmune diseases, particularly in T1D. Although evidence suggests that PPARs affect the b-cell function, their influence on T-cell responses and their potential impact on T1D remains largely unexplored. It was noted that PPARa is involved in restricting the transcription of IL17A and enhancing the expression of Foxp3 by minimizing its proteasomal degradation. Thus, antagonizing PPARs may exert beneficial effects in regulating the differentiation of CD4+ T cells and preventing T1D. Therefore, this review advocates for comprehensive investigations to delineate the precise roles of PPARs in T1D pathogenesis, offering innovative therapeutic avenues that target both the immune system and pancreatic function. This review paper seeks to bridge the knowledge gap between PPARs, immune responses, and T1D, providing insights that may revolutionize the treatment landscape for this autoimmune disorder. Moreover, further studies involving PPAR agonists in non-obese diabetic (NOD) mice hold promise for developing novel T1D therapies. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
34. An Insulin‐Inspired Supramolecular Hydrogel for Prevention of Type 1 Diabetes
- Author
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Zhongyan Wang, Yuna Shang, Mohan Liu, Dandan Feng, Chen Li, Jianfeng Liu, Zhimou Yang, and Xinxin Li
- Subjects
type 1 diabetes ,General Chemical Engineering ,medicine.medical_treatment ,General Physics and Astronomy ,Medicine (miscellaneous) ,02 engineering and technology ,Nod ,Autoantigens ,T-Lymphocytes, Regulatory ,01 natural sciences ,Immune tolerance ,Mice ,Mice, Inbred NOD ,Insulin ,General Materials Science ,NOD mice ,self‐assembled peptides ,education.field_of_study ,Full Paper ,autoimmunity ,General Engineering ,Hydrogels ,Full Papers ,021001 nanoscience & nanotechnology ,Female ,0210 nano-technology ,Adjuvant ,immunoregulation ,Science ,Population ,010402 general chemistry ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Islets of Langerhans ,Antigen ,medicine ,Animals ,Hypoglycemic Agents ,education ,Type 1 diabetes ,business.industry ,medicine.disease ,Peptide Fragments ,0104 chemical sciences ,Disease Models, Animal ,Diabetes Mellitus, Type 1 ,Immunology ,supramolecular hydrogels ,business - Abstract
Supramolecular peptide hydrogel has shown promising potential in vaccine development largely because of its ability to function both as antigen depot and immune adjuvant. Nap‐GdFdFdY, a tetrapeptide hydrogel that has been previously reported to exhibit adjuvant effect, is inadvertently found to contain conserved peptide sequence for insulin, proinsulin, and glutamic acid decarboxylase, 3 major autoantigens for the autoimmune type 1 diabetes (T1D). At present, despite being managed clinically with insulin replacement therapy, T1D remains a major health threat with rapidly increasing incidences, especially in children and young adults, and antigen‐specific immune tolerance induction has been proposed as a feasible approach to prevent or delay T1D progression at an early stage. Here, it is reported that innoculation of Nap‐GdFdFdY leads to complete protection of nonobese diabetic (NOD) mice from T1D development till the age of 36 weeks. Better maintenance of pancreatic islet morphology with minimal immune cell infiltration is also observed from mice exposed to Nap‐GdFdFdY. This beneficial impact is mainly due to its facilitative role on enhancing peripheral T regulatory cell (Treg) population, shown as increased splenic Treg percentage, and function, demonstrated by maintenance of circulating TGF‐β1 level. Serum cytokine microarray data further implicate a “buffering” role of Nap‐GdFdFdY on systemic inflammatory tone in NOD mice. Thus, with its versatility, applicability, and excellent potency, Nap‐GdFdFdY is posited as a novel therapeutic intervention for T1D., A hydrogel of Nap‐GdFdFdY containing conserved sequence of autoantigens including insulin, proinsulin, and glutamic acid decarboxylase as a novel therapeutic intervention for the autoimmune type 1 diabetes. Better pancreatic islet morphology with minimal immune cell infiltration is observed from mice with hydrogel because of enhancing peripheral T regulatory cell population and maintenance of circulating TGF‐β1 level.
- Published
- 2021
35. Point of view on the vaccination against COVID-19 in patients with autoimmune inflammatory rheumatic diseases
- Author
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Sander van Assen, Ulf Mueller-Ladner, Victoria Furer, Marc Bijl, Christien Rondaan, Karen Schreiber, Nancy Agmon-Levin, Klaus Warnatz, Nico M Wulffraat, Annette de Thurah, Daphna Paran, Meliha C Kapetanovic, and Ori Elkayam
- Subjects
Adult ,medicine.medical_specialty ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,Adolescent ,CLINICAL-COURSE ,Immunology ,Population ,Arthritis ,Autoimmunity ,Patient safety ,Young Adult ,Rheumatology ,Rheumatic Diseases ,Pandemic ,Immunology and Allergy ,Medicine ,Humans ,autoimmune diseases ,Young adult ,SYSTEMIC-LUPUS-ERYTHEMATOSUS ,Intensive care medicine ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,Clinical Trials as Topic ,OUTCOMES ,business.industry ,SARS-CoV-2 ,COVID-19 ,Middle Aged ,medicine.disease ,SERIES ,vaccination ,METHOTREXATE ,Vaccination ,Practice Guidelines as Topic ,Position paper ,Patient Safety ,ARTHRITIS ,business - Abstract
In view of the COVID-19 pandemic, there is an unmet clinical need for the guidelines on vaccination of patients with autoimmune inflammatory rheumatic diseases (AIIRD). This position paper summarises the current data on COVID-19 infection in patients with AIIRD and development of vaccines against COVID-19, discusses the aspects of efficacy and safety of vaccination, and proposes preliminary considerations on vaccination against COVID-19 in patients with AIIRD, mainly based on the expert opinion and knowledge on the use of other vaccines in this population of patients.
- Published
- 2021
36. Pathogenesis of psoriasis in the 'omic' era. Part I. Epidemiology, clinical manifestation, immunological and neuroendocrine disturbances
- Author
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Leszek Kalinowski, Magdalena Górecka-Sokołowska, Agata Płoska, Justyna Szczęch, Andrzej Slominski, Adrianna Radulska, Joanna Bartosińska, Marta Sobalska-Kwapis, Iwona T. Dobrucki, Dorota Krasowska, Roman Nowicki, Agnieszka Owczarczyk-Saczonek, Adam Reich, Radomir M. Slominski, Lawrence W. Dobrucki, Rafał Czajkowski, Anna Janaszak-Jasienicka, Dominik Samotij, Aneta Szczerkowska-Dobosz, Dorota Purzycka-Bohdan, Michał A. Żmijewski, Marta Macieja-Stawczyk, Edyta Reszka, Dominik Strapagiel, Anna Siekierzycka, Bogusław Nedoszytko, and Aleksandra Batycka-Baran
- Subjects
neoangiogenesis ,T cell ,Population ,Inflammation ,Dermatology ,Disease ,medicine.disease_cause ,Autoimmunity ,Pathogenesis ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Psoriasis ,medicine ,Immunology and Allergy ,education ,Internal medicine ,education.field_of_study ,Review Paper ,neurogenic inflammation ,business.industry ,autoimmunity ,psoriasis ,medicine.disease ,RC31-1245 ,medicine.anatomical_structure ,interleukins ,RL1-803 ,Immunology ,medicine.symptom ,business - Abstract
Psoriasis is a common, chronic, inflammatory, immune-mediated skin disease affecting about 2% of the world’s population. According to current knowledge, psoriasis is a complex disease that involves various genes and environmental factors, such as stress, injuries, infections and certain medications. The chronic inflammation of psoriasis lesions develops upon epidermal infiltration, activation, and expansion of type 1 and type 17 Th cells. Despite the enormous progress in understanding the mechanisms that cause psoriasis, the target cells and antigens that drive pathogenic T cell responses in psoriatic lesions are still unproven and the autoimmune basis of psoriasis still remains hypothetical. However, since the identification of the Th17 cell subset, the IL-23/Th17 immune axis has been considered a key driver of psoriatic inflammation, which has led to the development of biologic agents that target crucial elements of this pathway. Here we present the current understanding of various aspects in psoriasis pathogenesis.
- Published
- 2020
37. Comparison of tyrosinase antibody, tyrosinase-related protein-1 and -2 antibodies, melanin-concentrating hormone receptor antibody levels with autologous serum skin test and autologous plasma skin test results in patients with vitiligo
- Author
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Necmettin Akdeniz, Abdullah Ünal, Hatice Uce Özkol, and Yasemin Bayram
- Subjects
vitiligo ,Tyrosinase ,Vitiligo ,Dermatology ,medicine.disease_cause ,Autoimmunity ,In vivo ,medicine ,Immunology and Allergy ,Outpatient clinic ,antibodies ,TYRP1 ,skin and connective tissue diseases ,Internal medicine ,Original Paper ,integumentary system ,biology ,business.industry ,autoimmunity ,medicine.disease ,RC31-1245 ,Hormone receptor ,RL1-803 ,Immunology ,biology.protein ,autologous serum skin test ,Antibody ,business - Abstract
Introduction Although the exact etiopathogenesis of vitiligo is unknown, the autoimmunity hypothesis is much in evidence. The autologous serum skin test (ASST) and autologous plasma skin test (APST) are in vivo methods used in the diagnosis of some autoimmune diseases, which are easy and inexpensive to perform. Aim In this study, we investigated whether or not ASST and APST could determine autoimmunity in patients with vitiligo. Material and methods In this study, 30 vitiligo patients presenting to the dermatology outpatient clinic and 30 healthy volunteers without any known autoimmune diseases were included. Antibodies such as tyrosinase, tyrosinase-related protein-1 (TYRP1), tyrosinase-related protein-2 (TYRP2) and melanin-concentrating hormone receptor 1 (MCHR1) antibodies determined to be associated with vitiligo were examined. In addition, the association of these antibodies with the positivity of ASST and APST, which were suggested to be associated with autoimmunity, were examined. Results In our study, tyrosinase antibody was found to be significantly higher in vitiligo patients. ASST was positive in 12 (40%) patients with vitiligo and 8 (26.6%) control subjects. APST was positive in 8 (26.6%) of the patients with vitiligo and in 2 (6.6%) of the controls, and there was a significant difference between the groups in terms of APST positivity (p = 0.032). In addition, in our study, a significant correlation was found between TYRP1 antibody positivity and APST positivity in the patient group (p = 0.005). Conclusions These findings suggest that we may use APST to investigate the autoimmune etiopathogenesis of vitiligo.
- Published
- 2020
38. The Association of Subclinical Insulin Resistance with Thyroid Autoimmunity in Euthyroid Individuals
- Author
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Vesna Vucelić, Jelena Marinković, Milan Vrkljan, Krešimir Rotim, Domagoj Gajski, Kristina Blaslov, Petar Gaćina, and Gorana Mirošević
- Subjects
Adult ,Hashimoto thyroiditis ,medicine.medical_specialty ,endocrine system ,endocrine system diseases ,lcsh:Medicine ,Autoimmunity ,Hashimoto Disease ,Logistic regression ,Insulin resistance ,Internal medicine ,Humans ,Medicine ,Euthyroid ,Original Scientific Papers ,Subclinical infection ,biology ,business.industry ,lcsh:R ,5-hour oral glucose tolerance test ,General Medicine ,medicine.disease ,Anti-thyroid autoantibodies ,Endocrinology ,Homeostatic model assessment ,biology.protein ,Antibody ,business ,Follow-Up Studies - Abstract
SUMMARY Hashimoto thyroiditis is characterized by anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies that gradually lead to thyroid cell destruction. As hypothyroidism has been associated with insulin resistance (IR), we aimed to investigate whether IR is associated with thyroid antibody presence and whether the degree of IR correlates with their concentration in euthyroid individuals. A total of 164 non-diabetic, euthyroid individuals, average age 34 years, were included in the study, divided into two groups according to Hashimoto thyroiditis and underwent 5-hour oral glucose tolerance test. The degree of IR was evaluated by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The Hashimoto thyroiditis group had higher HOMA-IR (p=0.003) and lower glucose levels (p=0.04). HOMA-IR correlated positively with anti-TPO (p
- Published
- 2020
39. Autoimmune response after SARS-CoV-2 infection and SARS-CoV-2 vaccines.
- Author
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Hromić-Jahjefendić A, Lundstrom K, Adilović M, Aljabali AAA, Tambuwala MM, Serrano-Aroca Á, and Uversky VN
- Subjects
- Humans, Autoimmune Diseases immunology, Autoantigens immunology, COVID-19 immunology, COVID-19 prevention & control, SARS-CoV-2 immunology, COVID-19 Vaccines immunology, Autoimmunity immunology
- Abstract
The complicated relationships between autoimmunity, COVID-19, and COVID-19 vaccinations are described, giving insight into their intricacies. Antinuclear antibodies (ANA), anti-Ro/SSA, rheumatoid factor, lupus anticoagulant, and antibodies against interferon (IFN)-I have all been consistently found in COVID-19 patients, indicating a high prevalence of autoimmune reactions following viral exposure. Furthermore, the discovery of human proteins with structural similarities to SARS-CoV-2 peptides as possible autoantigens highlights the complex interplay between the virus and the immune system in initiating autoimmunity. An updated summary of the current status of COVID-19 vaccines is presented. We present probable pathways underpinning the genesis of COVID-19 autoimmunity, such as bystander activation caused by hyperinflammatory conditions, viral persistence, and the creation of neutrophil extracellular traps. These pathways provide important insights into the development of autoimmune-related symptoms ranging from organ-specific to systemic autoimmune and inflammatory illnesses, demonstrating the wide influence of COVID-19 on the immune system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
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40. Metal-induced autoimmunity in neurological disorders: A review of current understanding and future directions.
- Author
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Bjørklund G, Đorđević AB, Hamdan H, Wallace DR, and Peana M
- Subjects
- Humans, Nervous System Diseases immunology, Animals, Autoimmune Diseases immunology, Autoimmunity drug effects, Autoimmunity immunology, Metals adverse effects, Metals immunology
- Abstract
Autoimmunity is a multifaceted disorder influenced by both genetic and environmental factors, and metal exposure has been implicated as a potential catalyst, especially in autoimmune diseases affecting the central nervous system. Notably, metals like mercury, lead, and aluminum exhibit well-established neurotoxic effects, yet the precise mechanisms by which they elicit autoimmune responses in susceptible individuals remain unclear. Recent studies propose that metal-induced autoimmunity may arise from direct toxic effects on immune cells and tissues, coupled with indirect impacts on the gut microbiome and the blood-brain barrier. These effects can activate self-reactive T cells, prompting the production of autoantibodies, inflammatory responses, and tissue damage. Diagnosing metal-induced autoimmunity proves challenging due to nonspecific symptoms and a lack of reliable biomarkers. Treatment typically involves chelation therapy to eliminate excess metals and immunomodulatory agents to suppress autoimmune responses. Prevention strategies include lifestyle adjustments to reduce metal exposure and avoiding occupational and environmental risks. Prognosis is generally favorable with proper treatment; however, untreated cases may lead to autoimmune disorder progression and irreversible organ damage, particularly in the brain. Future research aims to identify genetic and environmental risk factors, enhance diagnostic precision, and explore novel treatment approaches for improved prevention and management of this intricate and debilitating disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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41. Citrullination of a phage-displayed human peptidome library reveals the fine specificities of rheumatoid arthritis-associated autoantibodies
- Author
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Gabriel D. Román-Meléndez, Rachel S. Quizon, Janelle M. Montagne, Daniel R. Monaco, H. Benjamin Larman, Maximilian F. Konig, Erika Darrah, and Mekbib Astatke
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Medicine (General) ,Phage display ,Proteome ,Arthritis ,Computational biology ,Disease ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Epitope ,Autoimmunity ,Arthritis, Rheumatoid ,Epitopes ,R5-920 ,Peptide Library ,medicine ,Human proteome project ,Humans ,Phage ImmunoPrecipitation Sequencing ,Rheumatoid arthritis ,Autoantibodies ,Peptidylarginine deiminase ,Autoantibody ,Citrullination ,General Medicine ,medicine.disease ,Medicine ,Research Paper - Abstract
Background Post-translational modifications (PTMs) on proteins can be targeted by antibodies associated with autoimmunity. Despite a growing appreciation for their intrinsic role in disease, there is a lack of highly multiplexed serological assays to characterize the fine specificities of PTM-directed autoantibodies. Methods In this study, we used the programmable phage display technology, Phage ImmunoPrecipitation Sequencing (PhIP-Seq), to profile rheumatoid arthritis (RA) associated anti-citrullinated protein antibody (ACPA) reactivities. Findings Using both unmodified and peptidylarginine deiminase (PAD)-modified phage display libraries consisting of ~250,000 overlapping 90 amino acid peptide tiles spanning the human proteome, PTM PhIP-Seq robustly identified antibodies to citrulline-dependent epitopes. Interpretation PTM PhIP-Seq was used to quantify key differences among RA patients, including PAD isoform specific ACPA profiles, and thus represents a powerful tool for proteome-scale antibody-binding analyses. Funding This research is based upon work supported in part by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA). The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of ODNI, IARPA, or the US Government. The US Government is authorized to reproduce and distribute reprints for governmental purposes notwithstanding any copyright annotation therein. This study was made possible by a National Institute of General Medical Sciences (NIGMS) grant R01 GM136724 (HBL). MFK was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grant T32AR048522. ED was supported by the Rheumatology Research Foundation.
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- 2021
42. An autoantigen profile from Jurkat T-Lymphoblasts provides a molecular guide for investigating autoimmune sequelae of COVID-19.
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Wang, Julia Y., Zhang, Wei, Roehrl, Michael W., Roehrl, Victor B., and Roehrl, Michael H.
- Abstract
In order to understand autoimmune phenomena contributing to the pathophysiology of COVID-19 and post-COVID syndrome, we have been profiling autoantigens (autoAgs) from various cell types. Although cells share numerous autoAgs, each cell type gives rise to unique COVID-altered autoAg candidates, which may explain the wide range of symptoms experienced by patients with autoimmune sequelae of SARS-CoV-2 infection. Based on the unifying property of affinity between autoAgs and the glycosaminoglycan dermatan sulfate (DS), this paper reports 140 candidate autoAgs identified from proteome extracts of human Jurkat T-cells, of which at least 105 (75%) are known targets of autoantibodies. Comparison with currently available multi-omic COVID-19 data shows that 125 (89%) DS-affinity proteins are altered at protein and/or RNA levels in SARS-CoV-2-infected cells or patients, with at least 94 being known autoAgs in a wide spectrum of autoimmune diseases and cancer. Protein alterations by ubiquitination and phosphorylation during the viral infection are major contributors of autoAgs. The autoAg protein network is significantly associated with cellular response to stress, apoptosis, RNA metabolism, mRNA processing and translation, protein folding and processing, chromosome organization, cell cycle, and muscle contraction. The autoAgs include clusters of histones, CCT/TriC chaperonin, DNA replication licensing factors, proteasome and ribosome proteins, heat shock proteins, serine/arginine-rich splicing factors, 14-3-3 proteins, and cytoskeletal proteins. AutoAgs, such as LCP1 and NACA, that are altered in the T cells of COVID patients may provide insight into T-cell responses to viral infection and merit further study. The autoantigen-ome from this study contributes to a comprehensive molecular map for investigating acute, subacute, and chronic autoimmune disorders caused by SARS-CoV-2. Based on the unique affinity between autoantigens (autoAgs) and dermatan sulfate (DS), this paper reports 140 candidate autoAgs identified from proteome extracts of Jurkat T-cells, with at least 105 (75%) being known targets of autoantibodies in various autoimmune diseases and cancer. Comparison with currently available multi-omic COVID-19 data shows that 125 (89%) DS-affinity proteins are altered in SARS-CoV-2-infected cells or patients. AutoAgs, such as LCP1 and NACA, that are altered in the T cells of COVID-19 patients may provide insight into T-cell responses during viral infection. [ABSTRACT FROM AUTHOR]
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- 2023
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43. An autoantigen-ome from HS-Sultan B-Lymphoblasts offers a molecular map for investigating autoimmune sequelae of COVID-19.
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Wang, Julia Y., Zhang, Wei, Roehrl, Victor B., Roehrl, Michael W., and Roehrl, Michael H.
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To understand how COVID-19 may induce autoimmune diseases, we have been compiling an atlas of COVID autoantigens (autoAgs). Using dermatan sulfate (DS) affinity enrichment of autoantigenic proteins extracted from HS-Sultan lymphoblasts, we identified 362 DS-affinity proteins, of which at least 201 (56%) are confirmed autoAgs. Comparison with available multi-omic COVID data shows that 315 (87%) of the 362 proteins are affected in SARS-CoV-2 infection via altered expression, interaction with viral components, or modification by phosphorylation or ubiquitination, at least 186 (59%) of which are known autoAgs. These proteins are associated with gene expression, mRNA processing, mRNA splicing, translation, protein folding, vesicles, and chromosome organization. Numerous nuclear autoAgs were identified, including both classical antinuclear antibodies (ANAs) and extractable nuclear antigens (ENAs) of systemic autoimmune diseases and unique autoAgs involved in the DNA replication fork, mitotic cell cycle, or telomerase maintenance. We also identified many uncommon autoAgs involved in nucleic acid and peptide biosynthesis and nucleocytoplasmic transport, such as aminoacyl-tRNA synthetases. In addition, this study found autoAgs that potentially interact with multiple SARS-CoV-2 Nsp and Orf components, including CCT/TriC chaperonin, insulin degrading enzyme, platelet-activating factor acetylhydrolase, and the ezrin-moesin-radixin family. Furthermore, B-cell-specific IgM-associated endoplasmic reticulum (ER) complex (including MBZ1, BiP, heat shock proteins, and protein disulfide-isomerases) is enriched by DS-affinity and up-regulated in B-cells of COVID-19 patients, and a similar IgH-associated ER complex was also identified in autoreactive pre-B1 cells in our previous study, which suggests a role of autoreactive B1 cells in COVID-19 that merits further investigation. In summary, this study demonstrates that virally infected cells are characterized by alterations of proteins with propensity to become autoAgs, thereby providing a possible explanation for infection-induced autoimmunity. The COVID autoantigen-ome provides a valuable molecular resource and map for investigation of COVID-related autoimmune sequelae and considerations for vaccine design. This paper investigates the autoantigenic proteome ('autoantigen-ome') of human B cells and shows that a large fraction of these DS-binding autoantigens is affected during SARS-CoV-2 infection, giving rise to a diverse pool of autoAgs that may lead to infection-induced autoimmune diseases. The COVID autoantigen-ome provided in this paper may serve as a molecular map and resource for investigating autoimmune phenomena of SARS-CoV-2 infection and its long-term sequelae. Understanding immunogenic proteins of COVID may also enhance vaccine target design. [ABSTRACT FROM AUTHOR]
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- 2023
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44. Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature
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Nicole Puertas Jurado, Edoardo Galli, David Bamert, Federica Sallusto, Sinduya Krishnarajah, Florian Ingelfinger, Hans H. Jung, Pascale Zwicky, Nicolás Gonzalo Núñez, Ayse Akarca, Sarah Mundt, Isabelle Opitz, Luca Piccoli, Donatella De Feo, Sebastian G. Utz, Didier Schneiter, Teresa Marafioti, Mirjam Lutz, Antonio Lanzavecchia, Michael Kramer, Burkhard Becher, Can Ulutekin, Bettina Schreiner, Corinne C Widmer, University of Zurich, Schreiner, Bettina, and Becher, Burkhard
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0301 basic medicine ,Male ,10255 Clinic for Thoracic Surgery ,T-Lymphocytes ,2804 Cellular and Molecular Neuroscience ,Autoimmunity ,Tissue-resident T cells ,Biomarker ,Mass cytometry ,Immunophenotyping ,Thymus ,Myasthenia gravis ,Cytokines ,medicine.disease_cause ,Machine Learning ,0302 clinical medicine ,Receptors, Cholinergic ,Aged, 80 and over ,B-Lymphocytes ,Middle Aged ,Thymectomy ,3. Good health ,medicine.anatomical_structure ,2728 Neurology (clinical) ,Female ,Single-Cell Analysis ,Adult ,T cell ,610 Medicine & health ,Thymus Gland ,Biology ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Immune system ,Myasthenia Gravis ,medicine ,Humans ,Aged ,Autoantibodies ,Autoimmune disease ,Original Paper ,Autoantibody ,Correction ,Immune dysregulation ,medicine.disease ,10040 Clinic for Neurology ,2734 Pathology and Forensic Medicine ,030104 developmental biology ,Immunology ,10032 Clinic for Oncology and Hematology ,Neurology (clinical) ,Biomarkers ,030215 immunology - Abstract
Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, the cellular and molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass and spectral cytometry of blood and thymus samples from MG patients in combination with supervised and unsupervised machine-learning tools to gain insight into the immune dysregulation underlying MG. By creating a comprehensive immune map, we identified two dysregulated subsets of inflammatory circulating memory T helper (Th) cells. These signature ThCD103 and ThGM cells populated the diseased thymus, were reduced in the blood of MG patients, and were inversely correlated with disease severity. Both signature Th subsets rebounded in the blood of MG patients after surgical thymus removal, indicative of their role as cellular markers of disease activity. Together, this in-depth analysis of the immune landscape of MG provides valuable insight into disease pathogenesis, suggests novel biomarkers and identifies new potential therapeutic targets for treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s00401-021-02299-y.
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- 2021
45. Sex and autoimmune disease: Four mechanisms pointing at women
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Angela Ceribelli, Maria De Santis, and Carlo Selmi
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Review Paper ,Modern medicine ,lcsh:Diseases of the musculoskeletal system ,business.industry ,autoimmunity ,microbiome ,twins ,Public relations ,Affect (psychology) ,Single patient ,Patient management ,Rheumatology ,estradiol ,Gender medicine ,Microbiome ,Personalized medicine ,sex chromosome ,lcsh:RC925-935 ,business ,Psychology ,autoantibody - Abstract
The ultimate goal of modern medicine is a personalized approach being tailored on the single patient, ie, tailored, based on a finely tuned definition of the immunogenetics, epigenetics, microbiome, and biomarkers, to maximize results and minimize risks particularly of new targeted treatments. Among individual factors around which to tailor the patient management are sex and age, with gender-medicine finally becoming central to the research agenda. Of note, we are not convinced that a whole personalized medicine approach in its current form will necessarily include gender medicine and thus this should remain central to the research agenda. To tackle this crucial issue, however, we should first be able to answer a question of paramount importance, that is, why does autoimmunity affect women more than men? The growing number of experimental works in this area militate against an easy answer to this question, but we will herein briefly discuss four major candidates (sex hormones, sex chromosomes, environmental factors, and the microbiome) to which some unsuspected others may be ancillary.
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- 2019
46. The role of pentraxin 3 in pemphigus vulgaris
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Ibrahim Halil Yavuz and Göknur Özaydın Yavuz
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Dermatology ,medicine.disease_cause ,Autoimmunity ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Immunology and Allergy ,pentraxin 3 ,Internal medicine ,Original Paper ,integumentary system ,biology ,Pentraxins ,Cell adhesion molecule ,business.industry ,Pemphigus vulgaris ,pemphigus ,autoimmune ,PTX3 ,medicine.disease ,RC31-1245 ,Pemphigus ,Desmoglein 1 ,RL1-803 ,Immunology ,biology.protein ,Antibody ,business - Abstract
Introduction Pemphigus is a group of autoimmune bullous diseases caused by antibodies directed against the desmosomal adhesion molecules desmoglein 1 and 3, which are required for intercellular adhesion of keratinocytes. Pentraxins are a group of proteins that function as pattern recognition molecules and also play a role in humoral innate immunity. Pentraxin 3 (PTX3) is the prototype of the long pentraxins and has been shown to be increased in numerous autoimmune diseases. Aim To investigate whether PTX3 can be used as a marker of PV caused by autoimmunity and resulting in tissue injury. Material and methods The study included 30 patients who presented to the University Medical School Dermatology Department and were diagnosed with PV based on clinical, histological, and immunological findings. The control group included 30 healthy individuals. Human PTX3 concentration was measured with a commercially available ELISA kit, using a double antibody sandwich enzyme-linked immunosorbent assay. Results The 60 participants comprised 31 (52%) men and 29 (48%) women. The most common site of onset was mucosa + skin (n = 22; 73.3%) and a psychological pathology was present in 7 (23.3%) patients. Median PTX3 level was significantly higher in the PV group compared to the control group (p = 0.008). The ROC curve analysis indicated a significant area under curve (AUC) value for serum PTX3 level in the prediction of PV. Conclusions PTX3 was found to be increased in PV and PTX3 could be a useful indicator of disease activity in PV.
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- 2019
47. Autoantibodies in Myositis. How to Achieve a Comprehensive Strategy for Serological Testing
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Miriam Mende, Wolfgang Schlumberger, Viola Borchardt-Lohölter, Thomas Scheper, and Wolfgang Meyer
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medicine.medical_specialty ,lcsh:Diseases of the musculoskeletal system ,dermatomyositis ,autoantibodies ,Arthritis ,serology ,medicine.disease_cause ,Polymyositis ,Autoimmunity ,polymyositis ,Rheumatology ,Medicine ,Myositis ,Review Paper ,business.industry ,autoimmunity ,Autoantibody ,Interstitial lung disease ,inclusion body myositis ,Dermatomyositis ,medicine.disease ,Dermatology ,Inclusion body myositis ,lcsh:RC925-935 ,business ,myositis - Abstract
Myopathies are a rare type of acquired, chronic autoimmune diseases of the skeletal muscles and affect both children and adults. The hallmark symptoms of idiopathic inflammatory myopathies (IIM) are muscle inflammation, proximal muscle weakness and disability, arthritis, cutaneous rashes, calcinosis, ulceration, malignancy and interstitial lung disease (ILD). Subforms of IIM include polymyositis, dermatomyositis, cancer-related myositis and sporadic inclusion body myositis. Autoantibodies function as biomarkers for diagnosis of IIM and can be used to delimit clinically distinguishable IIM subforms. To maximise the diagnostic information it is essential to perform comprehensive multiparametric serological testing including both screening and confirmation tests.
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- 2019
48. The immunological implication of the new vitamin D metabolism
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Luisa Agnello, Giulia Bivona, Marcello Ciaccio, Bivona, Giulia, Agnello, Luisa, and Ciaccio, Marcello
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0301 basic medicine ,Calcitriol ,Immunology ,lcsh:Medicine ,vitamin D ,medicine.disease_cause ,immunomodulation ,Calcitriol receptor ,Autoimmunity ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immune system ,CYPs ,CYP ,Vitamin D and neurology ,Immunology and Allergy ,Medicine ,VDR ,Calcium metabolism ,Review Paper ,Innate immune system ,business.industry ,autoimmunity ,lcsh:R ,030104 developmental biology ,chemistry ,business ,Cholecalciferol ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Vitamin D is a neuro-hormone regulating calcium-phosphate homeostasis, cell proliferation, and immunomodulation. exogenous and endogenous Vitamin D is inactive, and two hydroxylations are required to produce the active hormone. The first hydroxylation is unique to the liver, while the second step occurs in kidney, brain, lung, prostate, placenta, and immune cells. Kidney-derived calcitriol regulates calcium homeostasis. active hormone produced by brain and immune cells mediates immune system response; lung calcitriol is involved in fighting respiratory tract infections; finally, prostate and placenta Vitamin D regulates cells growth and proliferation within such tissues. immune modulation by Vitamin D includes enhancing innate immune response, attenuating and stimulating Th1 and Th2 cell proliferation, respectively, and promoting self-tolerance. Hypovitaminosis D is a common finding in several autoimmune diseases. it is unclear whether hypovitaminosis D could be a consequence or a cause of autoimmune diseases and whether Vitamin D supplementation has an impact on these patients. Moreover, there is no consensus on oral cholecalciferol dosage for supplementation. More interventional studies are required to better define how Vitamin D could represent both a causation agent in autoimmunity and a target for therapeutic strategies in autoimmune patients.
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- 2018
49. Quality of life in patients with primary biliary cholangitis: A cross-geographical comparison
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Marco Carbone, Daphne D’Amato, L. Jopson, Luca Vecchio, Sesé Pilar, Massimo Miglioretti, Lorenzo Montali, Martina Lucà, S. E. O'Donnell, A Gerussi, Clara Mancuso, Pietro Invernizzi, Andrea Gragnano, Albert Parés, Dave Jones, Anna Reig, Alessandra Frigerio, Minami Yagi, George F. Mells, Vincenzo Ronca, Atsushi Tanaka, Laura Cristoferi, Montali, L, Gragnano, A, Miglioretti, M, Frigerio, A, Vecchio, L, Gerussi, A, Cristoferi, L, Ronca, V, D’Amato, D, O’Donnell, S, Mancuso, C, Lucà, M, Yagi, M, Reig, A, Jopson, L, Pilar, S, Jones, D, Pares, A, Mells, G, Tanaka, A, Carbone, M, and Invernizzi, P
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Factorial invariance ,Research paper ,Cholestasis ,business.industry ,Cognitive domain ,Immunology ,Mean age ,Cognition ,Autoimmunity ,RC581-607 ,Quality of life ,Liver ,Cholestasi ,Immunology and Allergy ,Medicine ,In patient ,Sun exposure ,Immunologic diseases. Allergy ,business ,Emotional dysfunction ,Fatigue ,Demography - Abstract
Background & aims Several symptoms impair the quality of life (QoL) of patients with primary biliary cholangitis (PBC). They are reported to vary significantly in different countries. Aim of our study was to explore whether there is a geographical clustering that accounts for symptoms in PBC. Methods Data was analysed from four cohorts of PBC patients from the UK, Spain, Japan and Italy using the PBC-27 scale. Results Overall, 569 patients from four cohorts were identified, including 515 females (90.5%) with a mean age of 61 years. The analysis provided evidence for strict factorial invariance of the scale, a robust indicator of its validity for cross-cultural research. The mean of the fatigue domain of British patients was significantly greater than that of the Japanese (p , Graphical abstract Image 1, Highlights • Primary Biliary Cholangitis (PBC) is a rare liver disease characterised by several symptoms that impair quality of life; • This study includes data from questionnaires provided to individuals with PBC in Italy, Japan, Spain and United Kingdom; • It shows a clear geographical pattern of distribution of PBC-related symptoms, with a significant difference based on latitude.
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- 2021
50. A Systematic Review of the Potential Implication of Infectious Agents in Myasthenia Gravis.
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Leopardi, Victoria, Chang, Yu-Mei, Pham, Andrew, Luo, Jie, and Garden, Oliver A.
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MYASTHENIA gravis ,NEURAL transmission ,MYONEURAL junction ,SYMPTOMS ,DIAGNOSIS ,EPSTEIN-Barr virus - Abstract
Background: Myasthenia gravis (MG) is an autoimmune disorder of unknown etiology in most patients, in which autoantibodies target components of neuromuscular junctions and impair nerve to muscle transmission. Objective: To provide a synthesis of the evidence examining infectious agents associated with the onset of MG. Hypothesis: We hypothesized that microbes play a pathogenic role in the initiation of MG. For clinical cases, the onset of clinical signs is used as a proxy for the true onset of autoimmunity. Methods: We searched PubMed and Web of Science. Papers captured through database searching (n = 827) were assessed, yielding a total of 42 publications meeting the inclusion and exclusion criteria. An additional 6 papers were retrieved from the reference lists of relevant articles. For each pathogen, an integrated metric of evidence (IME) value, from minus 8 to plus 8, was computed based on study design, quality of data, confidence of infectious disease diagnosis, likelihood of a causal link between the pathogen and MG, confidence of MG diagnosis, and the number of infected patients. Negative IME values corresponded to studies providing evidence against a role for microbes as triggers of MG. Results: One hundred and sixty-nine myasthenic patients infected with 21 different pathogens were documented. Epstein-Barr virus (median = 4.71), human papillomavirus (median = 4.35), and poliovirus (median = 4.29) demonstrated the highest IME values. The total median IME was 2.63 (mean = 2.53; range −3.79–5.25), suggesting a general lack of evidence for a causal link. Conclusions: There was a notable absence of mechanistic studies designed to answer this question directly. The question of the pathogenic contribution of microbes to MG remains open. [ABSTRACT FROM AUTHOR]
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- 2021
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