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A Novel Hypothetical Approach to Explain the Mechanisms of Pathogenicity of Rheumatic Arthritis

The autoimmune disorder rheumatoid arthritis (RA) is a relapsing and chronic inflammatory disease that affects the synovial cells, cartilage, bone, and muscle. It is characterised by the accumulation of huge numbers of polymorphonuclear neutrophils (PMNs) and macrophages in the synovia. Auto-antibod...

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Detalles Bibliográficos
Autores principales: Feldman, Mark, Ginsburg, Isaac
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Mediterranean Journal of Rheumatology (MJR) 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369279/
https://www.ncbi.nlm.nih.gov/pubmed/34447906
http://dx.doi.org/10.31138/mjr.32.2.112
Descripción
Sumario:The autoimmune disorder rheumatoid arthritis (RA) is a relapsing and chronic inflammatory disease that affects the synovial cells, cartilage, bone, and muscle. It is characterised by the accumulation of huge numbers of polymorphonuclear neutrophils (PMNs) and macrophages in the synovia. Auto-antibodies are deposited in the joint via the activity of highly cationic histones released from neutrophil extracellular traps (NETs) in a phenomenon termed NETosis. The cationic histones function as opsonic agents that bind to negatively charged domains in autoantibodies and complement compounds via strong electrostatic forces, facilitating their deposition and endocytosis by synovial cells. However, eventually the main cause of tissue damage is the plethora of toxic pro-inflammatory substances released by activated neutrophils recruited by cytokines. Tissue damage in RA can also be accompanied by infections which, upon bacteriolysis, release cell-wall components that are toxic to tissues. Some amelioration of the damaged cells and tissues in RA may be achieved by the use of highly anionic heparins, which can neutralize cationic histone activity, provided that these polyanions are co-administrated with anti-inflammatory drugs such as steroids, colchicine, or methotrexate, low molecular weight antioxidants, proteinase inhibitors, and phospholipase A2 inhibitors.