Autoimmune rheumatic diseases and autoinflammatory syndromes, facets of contact

Abstract

Introduction The peculiarity of the development of inflammation, its acute and chronic course, various combinations of inflammatory mediators, the nature and severity of the immune response is largely arise from the genetic characteristics of the organism. It would be logical to assume the key role of small mutations of genes in initiating the development of autoaggression, activation of signaling molecules, immunocompetent cells with violation of their cooperation, production of pro-inflammatory cytokines, as a consequence of the effect of persistent viral-bacterial infection and non-infectious agents. In this regard, the comparative analysis of pathogenetic mechanisms of development, clinical symptoms of autoimmune rheumatic diseases and genetically determined autoinflammatory syndromes (AIDs), the mutation of genes in the development of many of them has already been proved, would be interesting. Material & methods The article is compiled based on the publications review. Results & discussion At the heart of the development of autoimmune rheumatic diseases lie mostly the changes in the system of immunobiological surveillance, the adaptive link of immunity. The elimination of T-lymphocyte anergy to autoantigens, increased activity and expansion of clones of T and B lymphocytes, the production of circulating autoantibodies upon activation of signaling pathways / molecules, the secretion of proinflammatory cytokines (IL-1,6, TNF-α) are the key links in immunopathogenesis of rheumatic diseases The spectrum of autoimmune rheumatic diseases differs in adults and children. Only children suffer from juvenile idiopathic arthritis, juvenile dermatomyositis, neonatal lupus, Kawasaki disease, and acute rheumatic fever. Both children and adults suffer from systemic lupus erythematosus, systemic vasculitis, antiphospholipid syndrome, and systemic scleroderma. Dominant symptoms in the debut of autoimmune rheumatic diseases are prolonged fever, skin-vascular syndrome, serositis, arthralgia, arthritis, myalgia, myositis, high laboratory activity indicators. In contrast with most autoimmune disease auto-inflammatory syndroms usually present during childhood. AIDs is a heterogeneous group of rare, genetically determined states characterized by unprovoked attacks of inflammation and manifested by fever and clinical symptoms resembling rheumatic ones in the absence of autoantibodies and / or antigen-specific T-lymphocytes. Diseases of this group have both common and distinctive features that correspond to the Eurofever register of more than 21 nosological forms, including congenital recurrent febrile syndromes, cryopyrin-associated periodic syndromes, granulomatous and pyogenic diseases, proteasome deficiency, chronic recurrent multifocal osteomyelitis. Unlike of autoimmune diseases, the main role in the initiation of autoinflammatory syndromes is played by mutations in genes involved in the realization of the immune response of the innate immunity system, as well as non-antigen-induced antibody synthesis or activation of T and β-lymphocytes. A special place, as a trigger mechanism, in the development of autologous means, belongs to the multiplate cytoplasmic complex formed in neutrophils and macrophages - an inflamasome regulating the secretion of pro-inflammatory cytokines and, as a consequence, triggering an inflammatory response upon contact of cells with infectious and non-infectious agents. The composition of the inflamasome includes proteins encoded by genes, the specific mutations of which cause the development of AIDs. Most clearly, the inflamasomes role in the pathogenesis of AIDs can be traced to the example of Cryopyrin-associated Periodic Syndromes (CARS), including Familial Cold Auto-inflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS) and Chronic Infantile Onset Neurological Cutaneous Articular/ Neonatal Onset Multi-systemic Inflammatory Disease - CINCA / NOMID syndrome. All three problems are caused by a mutation of the CIASI gene located in the long arm of the first pair of chromosomes and encoding the cryopyrin protein (NLRR3). Despite differences in pathogenesis and distinctive features of a course of diseases, the targets of inflammatory reaction in the compared groups of autoimmune rheumatic diseases and autoinflammatory syndromes are identical: the skin, joints, serous coverings, and the central nervous system. The complication of both syndromes is the development of AA-amyloidosis, and multi-organ failure. Conclusion Perhaps the disclosure, the understanding of more subtle mechanisms of development, the cyclicity of the autoinflammatory process, the spontaneous arrest of the inflammatory response, unprovoked relapse attacks, as well as the determination of the carriage of pathogenic mutations of genes responsible for the development of AIDs in patients with autoimmune rheumatic diseases, will help to identify that disturbed link in the general chain of interconnection of cells of congenital and adaptive immunity, which is a key factor in the development of autoaggression. So in order to deepen our understanding of human innate immunity, and to offer more targeted therapies for patients with autoimmune rheumatic diseases, further studies on the genetics and molecular pathophysiology of autoimmune rheumatic and autoinflammatory diseases are essential.

DOI: 10.5281/zenodo.4382141