Review article

Pathogenesis of rheumatoid arthritis

Branimir Anić ; Department for Clinical Immunology and Rheumatology, Clinic for Internal Medicine of the School of Medicine, University of Zagreb, Clinical Hospital Centre Zagreb, Zagreb, Croatia
Miroslav Mayer ; Department for Clinical Immunology and Rheumatology, Clinic for Internal Medicine of the School of Medicine, University of Zagreb, Clinical Hospital Centre Zagreb, Zagreb, Croatia

Abstract

Rheumatoid arthritis (RA) is an autoimmune systemic disease that primarily affects joints. Etiology and the pathogenesis of RA are complex, involving many types of cells, among others macrophages, T and B cells, fibroblasts, chondrocytes and dendritic cells.
Despite well documented role of many genes and epigenetic modifications in the development and evolution of the disease, in most RA patients there is no clear predisposing factor present. Environmental factors involved in RA pathogenesis are cigarette smoke, industrial pollutants like silica crystals, disturbances of intestinal, lung, and oral microbiota and some specific bacterial and viral infectious agents and their components.
In the initial disease stage there are qualitative and quantitative disturbances of peptide citrulination as well as other protein modifications, followed by antigen presenting cell (APC) (macrophages and dendritic cells) and fibroblast like synoviocytes (FLS) activation. Some microbes foster this processes by APC and FLS direct and indirect activation. In the second stage APC’s elicit specific humoral B cell response resulting in specific antibodies production and T cell autoreactivity. Inherited and acquired defects in T and B cell responses caused by repeated activation of innate immunity as well as loss of tolerance, elicit chronic autoimmune inflammation, primarily of synovial membranes, and development of cellular panus. Pathologic activation of the osteoclasts and release of the immune system effector molecules and the proteolytic enzymes damage the cartilage, bone and tendons composition and structure.
Persistent inflammation through its complex mechanisms results in many systemic and extraarticular RA manifestations of almost all organ systems, resulting in severe complications and comorbidities such as rheumatoid lung, carditis, vasculitis, cahexia, anemia, accelerated atherosclerosis, myocardial and cerebrovascular vascular disease, lymphoma, osteoporosis, depression etc. Accumulated complications and comorbidities finally result in handicap, social dysfunction and premature death.

Keywords

rheumatoid arthritis; pathogenesis; etiology; smoking

Hrčak ID:

137892

URI

https://hrcak.srce.hr/137892

Publication date:

23.10.2014.

Article data in other languages: croatian

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