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Joint Bone Spine May 2017
Review
Topics: Animals; Autoantigens; Autoimmune Diseases; Autoimmunity; Chronic Disease; Evidence-Based Medicine; Genetic Predisposition to Disease; Humans; Prevalence; Prognosis; Risk Assessment
PubMed: 28017820
DOI: 10.1016/j.jbspin.2016.11.012 -
Clinical and Experimental Immunology Apr 2019Dendritic cells (DCs) are the key professional antigen-presenting cells which bridge innate and adaptive immune responses, inducing the priming and differentiation of... (Review)
Review
Dendritic cells (DCs) are the key professional antigen-presenting cells which bridge innate and adaptive immune responses, inducing the priming and differentiation of naive to effector CD4 T cells, the cross-priming of CD8 T cells and the promotion of B cell antibody responses. DCs also play a critical role in the maintenance of immune homeostasis and tolerance. DC-T cell interactions underpin the generation of an autoimmune response in rheumatoid arthritis (RA). Here we describe the function of DCs and review evidence for DC and T cell involvement in RA pathogenesis, in particular through the presentation of self-peptide by DCs that triggers differentiation and activation of autoreactive T cells. Finally, we discuss the emerging field of targeting the DC-T cell interaction for antigen-specific immunotherapy of RA.
Topics: Animals; Antibody Formation; Antigen Presentation; Arthritis, Rheumatoid; Autoantigens; Autoimmunity; B-Lymphocytes; Cell Communication; Dendritic Cells; Humans; Immune Tolerance; Immunotherapy; Lymphocyte Activation; Peptides; T-Lymphocytes
PubMed: 30589082
DOI: 10.1111/cei.13256 -
Autoimmunity Reviews Sep 2020Candida albicans is a commensal fungus with a potential pathogenicity and celiac disease is an autoimmune condition. Both share multiple pathophysiological junctions,... (Review)
Review
Candida albicans is a commensal fungus with a potential pathogenicity and celiac disease is an autoimmune condition. Both share multiple pathophysiological junctions, including serological markers against cell-wall proteins of Candida, anti-gliadin antibodies are positive in both entities, gluten and a candidal virulence factor share sequence similarity and the autoantigen of celiac disease, the tissue transglutaminase, is pivotal in Candida albicans commensalism and hostile behavior and its covalently cross linked products are stable and resistant to breakdown in the two entities. Those autoimmune/infectious cross roads are the basis for the hypothesis that Candida albicans is an additional environmental factor for celiac disease autoimmunogenesis.
Topics: Antibodies; Autoantigens; Autoimmunity; Candida albicans; Celiac Disease; Gliadin; Humans; Transglutaminases; Virulence Factors
PubMed: 32693029
DOI: 10.1016/j.autrev.2020.102621 -
Journal of Leukocyte Biology Sep 2017Neutrophils are critical in the defense against bacterial and fungal pathogens, and they also modulate the inflammatory process. The areas where neutrophils are studied... (Review)
Review
Neutrophils are critical in the defense against bacterial and fungal pathogens, and they also modulate the inflammatory process. The areas where neutrophils are studied have expanded from the restricted field of antibacterial defense to the modulation of inflammation and finally, to fine-tuning immune responses. As a result, recent studies have shown that neutrophils are implicated in several systemic autoimmune diseases, although exactly how neutrophils contribute to these diseases and the molecular mechanisms responsible are still under investigation. In a group of autoimmune vasculitides associated with anti-neutrophil cytoplasmic antibodies (AAVs), granulomatosis with polyangiitis (GPA) illustrates the concept that autoimmunity can develop against one specific neutrophil protein, namely, proteinase 3 (PR3), one of the four serine protease homologs contained within azurophilic granules. In this review, we will focus on recent molecular analyses combined with functional studies that provide clear evidence that the pathogenic properties of PR3 are not only a result of its enzymatic activity but also mediated by a particular structural element-the hydrophobic patch-which facilitates associations with various proteins and lipids and permits anchorage into the plasma membrane. Furthermore, these unique structural and functional characteristics of PR3 might be key contributors to the systemic inflammation and to the immune dysregulation observed in GPA.
Topics: Animals; Antibodies, Antineutrophil Cytoplasmic; Autoantigens; Autoimmune Diseases; Granulomatosis with Polyangiitis; Humans; Myeloblastin; Neutrophils; Structure-Activity Relationship
PubMed: 28546501
DOI: 10.1189/jlb.3MR0217-069R -
Nature Reviews. Rheumatology Mar 2018Dysregulation of lymphocyte function, accumulation of autoantibodies and defective clearance of circulating immune complexes and apoptotic cells are hallmarks of... (Review)
Review
Dysregulation of lymphocyte function, accumulation of autoantibodies and defective clearance of circulating immune complexes and apoptotic cells are hallmarks of systemic lupus erythematosus (SLE). Moreover, it is now evident that an intricate interplay between the adaptive and innate immune systems contributes to the pathogenesis of SLE, ultimately resulting in chronic inflammation and organ damage. Platelets circulate in the blood and are chiefly recognized for their role in the prevention of bleeding and promotion of haemostasis; however, accumulating evidence points to a role for platelets in both adaptive and innate immunity. Through a broad repertoire of receptors, platelets respond promptly to immune complexes, complement and damage-associated molecular patterns, and represent a major reservoir of immunomodulatory molecules in the circulation. Furthermore, evidence suggests that platelets are activated in patients with SLE, and that they could contribute to the circulatory autoantigenic load through the release of microparticles and mitochondrial antigens. Herein, we highlight how platelets contribute to the immune response and review evidence implicating platelets in the pathogenesis of SLE.
Topics: Adaptive Immunity; Alarmins; Antigen-Antibody Complex; Autoantigens; Blood Platelets; Complement System Proteins; Humans; Immunity, Innate; Lupus Erythematosus, Systemic
PubMed: 29559714
DOI: 10.1038/nrrheum.2018.38 -
Nature Reviews. Neurology Sep 2020A rapidly expanding and clinically distinct group of CNS diseases are caused by pathogenic autoantibodies that target neuroglial surface proteins. Despite immunotherapy,... (Review)
Review
A rapidly expanding and clinically distinct group of CNS diseases are caused by pathogenic autoantibodies that target neuroglial surface proteins. Despite immunotherapy, patients with these neuroglial surface autoantibody (NSAb)-mediated diseases often experience clinical relapse, high rates of long-term morbidity and adverse effects from the available medications. Fundamentally, the autoantigen-specific B cell lineage leads to production of the pathogenic autoantibodies. These autoantigen-specific B cells have been consistently identified in the circulation of patients with NSAb-mediated diseases, accompanied by high serum levels of autoantigen-specific antibodies. Early evidence suggests that these cells evade well-characterized B cell tolerance checkpoints. Nearer to the site of pathology, cerebrospinal fluid from patients with NSAb-mediated diseases contains high levels of autoantigen-specific B cells that are likely to account for the intrathecal synthesis of these autoantibodies. The characteristics of their immunoglobulin genes offer insights into the underlying immunobiology. In this Review, we summarize the emerging knowledge of B cells across the NSAb-mediated diseases. We review the evidence for the relative contributions of germinal centres and long-lived plasma cells as sources of autoantibodies, discuss data that indicate migration of B cells into the CNS and summarize insights into the underlying B cell pathogenesis that are provided by therapeutic effects.
Topics: Animals; Autoantibodies; Autoantigens; Autoimmune Diseases; B-Lymphocytes; Central Nervous System Diseases; Humans; Immunotherapy
PubMed: 32724223
DOI: 10.1038/s41582-020-0381-z -
International Journal of Molecular... Feb 2020Autoantigen treatment has been tried for the prevention of type 1 diabetes (T1D) and to preserve residual beta-cell function in patients with a recent onset of the... (Review)
Review
Autoantigen treatment has been tried for the prevention of type 1 diabetes (T1D) and to preserve residual beta-cell function in patients with a recent onset of the disease. In experimental animal models, efficacy was good, but was insufficient in human subjects. Besides the possible minor efficacy of peroral insulin in high-risk individuals to prevent T1D, autoantigen prevention trials have failed. Other studies on autoantigen prevention and intervention at diagnosis are ongoing. One problem is to select autoantigen/s; others are dose and route. Oral administration may be improved by using different vehicles. Proinsulin peptide therapy in patients with T1D has shown possible minor efficacy. In patients with newly diagnosed T1D, subcutaneous injection of glutamic acid decarboxylase (GAD) bound to alum hydroxide (GAD-alum) can likely preserve beta-cell function, but the therapeutic effect needs to be improved. Intra-lymphatic administration may be a better alternative than subcutaneous administration, and combination therapy might improve efficacy. This review elucidates some actual problems of autoantigen therapy in the prevention and/or early intervention of type 1 diabetes.
Topics: Administration, Oral; Animals; Autoantigens; Chemotherapy, Adjuvant; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Glutamate Decarboxylase; Humans; Injections, Intralymphatic; Injections, Subcutaneous; Insulin; Proinsulin; Vitamin D
PubMed: 32111075
DOI: 10.3390/ijms21051598 -
International Immunopharmacology Mar 2023Autoimmune diseases are caused by the dysfunction of the body's immune regulatory system, which leads to the recognition of self-antigens and the destruction of... (Review)
Review
Autoimmune diseases are caused by the dysfunction of the body's immune regulatory system, which leads to the recognition of self-antigens and the destruction of self-tissues and is mediated by immune cells such as T and B cells, and affects 5-10% of the population worldwide. Current treatments such as non-steroidal anti-inflammatory drugs and glucocorticoids can only relieve symptoms of the disease and are accompanied by serious side effects that affect patient quality of life. The recent rise in antigen-specific therapies, especially vaccines carrying autoantigenic peptides, promises to change this disadvantage, where research has increased dramatically in the last decade. This therapy established specific immune tolerance by delivering peptide fragments containing disease-specific self-antigen epitopes to suppress excessive immune responses, thereby exerting a therapeutic effect, with high safety and specificity. This article presents the latest progress on the treatment of autoimmune diseases with autoantigen peptide vaccines. It includes the construction of peptide vaccine delivery system, the mechanism of inducing immune tolerance and its application.
Topics: Humans; Quality of Life; Autoimmune Diseases; Immune Tolerance; Vaccines; Autoantigens; Vaccines, Subunit
PubMed: 36696858
DOI: 10.1016/j.intimp.2023.109740 -
Rheumatology (Oxford, England) Mar 2020Anti-transcription intermediary factor 1 (TIF1)-γ autoantibodies are robustly linked with cancer-associated DM in adults. This review aims to give an overview of the... (Review)
Review
Anti-transcription intermediary factor 1 (TIF1)-γ autoantibodies are robustly linked with cancer-associated DM in adults. This review aims to give an overview of the physiological context of TIF1-γ and to determine whether there is a pathophysiological link between anti-TIF1-γ autoantibodies and the occurrence of cancer. Detection of anti-TIF1-γ autoantibodies has a high sensitivity and specificity for cancer-associated DM in adults and is therefore useful for both diagnosis and cancer risk stratification. The function of the autoantigen, TIF1-γ, may provide insight into the mechanism behind this association. TIF1-γ is a ubiquitously present protein involved in various biological pathways, including TGF-β signalling. In cancer, it can act either as a tumour suppressor or promoter, depending on the cellular context and cancer stage. Evolving data provide pathophysiological insights, linking anti-TIF1-γ autoantibodies to both the anti-tumour response and to muscle and skin damage. TIF1-γ expression is increased in muscle and skin tissue of patients with DM. Mutations or loss-of-heterozygosity in TIF1-γ alleles in malignant tissue may result in the expression of tumour-specific neo-antigens stimulating autoantibody production. The newly formed autoantibodies are hypothesized to cross-react with antigens in muscle and skin, driving the development of DM. Based on the current evidence, anti-TIF1-γ autoantibodies should be considered warning lights of a potential tumour autoantigen and should alert the physician to the possibility of an underlying cancer.
Topics: Autoantibodies; Autoantigens; Dermatomyositis; Humans; Transcription Factors
PubMed: 31883334
DOI: 10.1093/rheumatology/kez572 -
Clinical and Experimental Immunology Dec 2019In recent years, there have been exciting new insights into pathogenesis of type 1 diabetes in a number of areas of immunology. In this edition, a collection of four...
In recent years, there have been exciting new insights into pathogenesis of type 1 diabetes in a number of areas of immunology. In this edition, a collection of four review articles are presented, which encompass new findings presented at the Immunology of Diabetes Society meeting in London 2018. The articles are focused particularly in 4 related areas of investigation, which include autoantibodies in type 1 diabetes, new autoantigenic targets for CD4 T cells, trafficking of immune cells to the pancreas and islet-immune interactions in the pancreas.
Topics: Autoantibodies; Autoantigens; CD4-Positive T-Lymphocytes; Diabetes Mellitus, Type 1; Humans; Islets of Langerhans; Pancreas
PubMed: 31729755
DOI: 10.1111/cei.13396