The Clinicopathologic Significance of Inflammasome Activation in Autoimmune Diseases

AbstractAutoimmune diseases are characterized by dysregulated immune tolerance to self and inflammatory damage to tissues and organs. The development of inflammation involves multiple innate and adaptive immune pathways. Inflammasomes are multimeric cytosolic protein complexes that form to mediate host immune responses upon recognizing pathogen ‐ or danger‐associated molecular patterns via pattern recognition receptors (PRRs). The accelerating pace of inflammasome research has demonstrated important roles for inflammasome activation in many pathologic conditions encompassing infectious, metabolic, autoinflammatory, and autoimmune disea ses. The inflammasome is generally comprised of a PRR, pro‐caspase‐1 and an adaptor molecule connecting the PRR and pro‐caspase‐1. With inflammasome activation, pro‐caspase‐1 becomes active caspase‐1 that converts pro‐IL‐1β and pro‐IL‐18 into mature and active IL‐1β and IL‐ 18, respectively. Having multipotent effects on immune and non‐immune cells, the cytokines IL‐1β and IL‐18 induce and promote systemic and local inflammatory responses. Human studies have reported increased levels of these cytokines, altered activation of inflammasome‐related molecules, and /or presence of inflammasome activators in rheumatic diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), crystal‐induced arthropathies, and Sjögren's syndrome. Such changes are found in the primary t...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: REVIEW ARTICLE Source Type: research

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Conclusions: Substantial AID heterogeneity exists by race and by geographic area. An important research area is further exploring factors related to heterogeneity such as potential interactions between genetic susceptibility and environmental factors.
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
Conclusions The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Asthma and allergy Original Articles: Asthma and allergy Source Type: research
Abstract Autoimmune diseases, such as rheumatoid arthritis, systematic lupus erythematosus and Sjögren's syndrome, are a group of diseases characterized by the activation of immune cells and excessive production of autoantibodies. Although the pathogenesis of these diseases is still not completely understood, studies have shown that multiple factors including genetics, environment and immune responses play important roles in the development and progression of the diseases. In China, there are great achievements in the mechanisms of autoimmune diseases during the last decades. These studies provide new insight...
Source: Advances in Immunology - Category: Allergy & Immunology Authors: Tags: Adv Immunol Source Type: research
Authors: El Jammal T, Gerfaud-Valentin M, Sève P, Jamilloux Y Abstract In the past ten years, the better understanding of the pathophysiological mechanisms underlying inflammatory and autoimmune diseases has led to the emergence of many targeted therapies. Among them, the Janus kinase inhibitors are acting upstream in the inflammatory cascade of several key cytokines in disorders such as rheumatoid arthritis, ulcerative colitis or psoriasis. At the moment, these three diseases represent the only indications validated by the FDA and the EMA of the use of JAK inhibitors apart from hematology. Preclinical data ...
Source: Revue de Medecine Interne - Category: Internal Medicine Tags: Rev Med Interne Source Type: research
CONCLUSIONS: According to the proposed algorithm, ANA IIF+MFI- subjects should be screened by an alternative solid-phase assay such as line-immunoassay or ELISA. PMID: 31694754 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Rheumatology - Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research
AbstractThe idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases resulting from inflammation of muscle and manifesting as weakness, though a range of extra-muscular manifestations are observed. These are often correlated closely with disease subtype and the presence of myositis-specific/myositis-associated antibodies. IIM are notoriously difficult to treat and often refractory to glucocorticoid therapy and synthetic immunosuppressants. Both the innate and adaptive immune systems are implicated in the pathogenesis of IIM. A growing understanding of the key cytokines as well as the cell-mediated and an...
Source: Rheumatology International - Category: Rheumatology Source Type: research
Neutrophil Extracellular Traps (NETs) are produced by neutrophilic granulocytes and consist of decondensed chromatin decorated with antimicrobial peptides. They defend the organism against intruders and are released upon various stimuli including pathogens, mediators of inflammation, or chemical triggers. NET formation is also involved in inflammatory, cardiovascular, malignant diseases, and autoimmune disorders like rheumatoid arthritis, psoriasis, or systemic lupus erythematosus (SLE). In many autoimmune diseases like SLE or dermatomyositis, light of the ultraviolet-visible (UV-VIS) spectrum is well-known to trigger and ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionThis study for the first time ever reveals the association of IRAK2 rs708035 and IRAK2 rs3844283 and the corresponding haplotypes with SLE. Our findings give additional rationale to target IRAKs in the treatment of SLE.Key Points•IRAK2 rs708035 A allele is more frequent in SLE patients than in controls and IRAK2 rs3844283 G allele is associated with SLE susceptibility.•These two alleles are in linkage disequilibrium.•The AG haplotype is associated with SLE.
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
Abstract In Western countries, about 5% of the population is affected by an autoimmune disease; in the United States, up to 23.5 million Americans suffer from autoimmune disorders [1]. Women comprise over 80% of the affected individuals for many autoimmune conditions, including Sjögren's syndrome, systemic sclerosis, Addison's disease, primary biliary cirrhosis, systemic lupus erythematosus (SLE), and autoimmune thyroid diseases like Grave's disease and Hashimoto's thyroiditis [2]. Additionally, the prevalence of rheumatoid arthritis, multiple sclerosis, and Sjögren's syndrome is also skewed towards wome...
Source: Clinical Immunology - Category: Allergy & Immunology Authors: Tags: Clin Immunol Source Type: research
Abstract Several reports have highlighted the abnormal increments of serum immunoglobulin free light chains (FLC) in the course of systemic autoimmune rheumatic diseases (SARD) but a comparative analysis among different conditions is still lacking. A strong association between elevated FLC and HCV-related mixed cryoglobulinaemia (HCVMC) has been well established. Here, we aimed to analyze serum FLC levels in patients with four different SARDs in comparison with HCVMC. Using a turbidimetric assay, free k and λ chains were quantified in sera from 198 SARD patients (37 Rheumatoid Arthritis, RA; 47 Systemic Lup...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research
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