Pathophysiology of RA

The pathophysiology of RA

The pathophysiology of RA involves the release of pro-inflammatory cytokines, especially TNF- and IL-6, which cause synovial membrane destruction. A multitude of immune modulators, either cytokines or cell effects, signal the route in the pathogenesis of RA (Ehrenstein et al. 276). A complicated combination of immune modulators causes the joint damage that covers most IA structures. Synovitis is caused by the influx and/or local activation of mononuclear cells such as B cells, plasma cells, mast cells, macrophages, dendrites, and T-cells via angiogenesis. As the synovial lining becomes hyperplastic, the synovial membrane, which is rich in osteoclasts, stretches to generate villi. The pannus destroys the bones while enzymes from neutrophils, chondrocytes and synoviocytes corrode the cartilage (Begovich et al. 331).

Progression of RA

While the disease starts by affecting the small joints, mainly hands, feet, and the cervical spine, severe erosion of joint surface affects the patient. With time and no treatment, the minor symptoms of swollen and tender warm joints become stiff and severely painful (Ehrenstein et al. 281). Other symptoms that come with increased severity of the disease include skin inflammation, fibrosis and Caplan’s syndrome in the lungs, renal amyloidosis in kidneys, atherosclerosis, heart attack and endocarditis in the heart, and scleritis in the eyes (Choy 304).

Phylogenic analysis and its importance

Phylogenic analysis helps distinguish RA from other diseases with similar symptoms. The analysis is also an important component of the study of the disease as it helps to understand what genes are involved in the pathogenesis. It is hence important in research for the control of the disease.

Controlling RA through gut microbiota

The advent and progression of RA can be controlled by the manipulation of gut commensals through mucosal modulation. We will use arthritis susceptible mice, carrying HLA-DRBI, *0401 and *0402 genes (Ehrenstein et al. 279), to determine if differences in gut microbiota have an impact on the susceptibility of to RA.

References

Begovich, Ann B., Victoria E. H. Carlton, Lee A. Honigberg, Steven J. Schrodi, Anand P. Chokkalingam, Heather C. Alexander, Kristin G. Ardlie, Qiqing Huang, Ashley M. Smith, Jill M. Spoerke, Marion T. Conn, Monica Chang, …, & Peter K. Gregersen “A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis”. The American Journal of Human Genetics, vol. 75, no. 2, 2004, pp. 330-337.

Ehrenstein, Michael R., Jamie G. Evans, Animesh Singh, Samantha Moore, Gary Warnes, David A. Isenberg, & Claudia Mauri ”Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFα therapy”. Journal of Experimental Medicine, vol. 200, no. 3, 2004, pp. 277-285.