pa tho genesis of rheumatoid arthritis

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Pathogenesis of Rheumatoid Arthritis

Autoimmune diseases require that the affected individual have a defect in the ability to

distinguish self from foreign molecules. There are markers on many cells that allow the

immune system to identify self. However, some markers allow for RA to happen regardless

of the markers that may label cells as self. There are obvious factors to rheumatoid arthritis,

and why it is an autoimmune disease, but the exact cause of this systemic disease is still

elusive because several immunopathogenic mechanisms work analogously to cause this

autoimmune disease (Smith, 2006). Patients with RA undergo a variation of possible changes

and create an initial immune response to a host molecule that uses molecular mimicry to look

like a foreign molecule, which the body then attacks. Due to several changes, RA can be

categorized as a Type III, immune complex disease, which involves immune complexes

containing autoantibodies against soluble autoantigens; or it can be categorized as a Type IV,

T-cell mediated disease, which involves an unknown synovial joint antigen as its autoantigen

to affect the T cell and antibody-mediated pathways and cause tissue injury (Janeway, 2005).

Both factors are important to the pathogenesis of RA.

As an immune complex disease, an autoantibody called rheumatoid factor has been

found among 80% of RA patients (Goldbach-Mansky et. al., 2000). In a study conducted by

Goldback-Manskeyet. al., a strong correlation between RA and rheumatoid factor was found.

There may be other autoantibodies which develop in different stages of the disease, but the

rheumatoid factor seems to be the most prominent and prevalent (2000). The rheumatoid

factor itself is an IgM anti-IgG antibody that is produced in normal immune responses to a

severe infection or immunization (Janeway, 2005). T cells are stimulated in an antigen-

independent manner, create an abundance of cytokines, interact with enough


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IgGautoantigencomplexes, stimulate ignorant B cells, and then a rheumatoid factor response

can be made to bind the Fc fragment of the host's IgG molecule and cause the inflammation

that is characteristic of RA (Janeway, 2005).

Rheumatoid arthritis is also a T-cell mediated disease, which is the more commonly

known consequence for this autoimmune disease. The pathology of RA also extends as a T-

cell mediated disease throughout the synovial along with other organs. In contrast to normal

synovial fluid, RA synovial fluid is completely enriched with macrophages, neutrophils, T

lymphocytes, and dendridic cells. There are many more cells present in the RA synovial fluid

that the joint naturally increases from 1-2 cells in width to 6-8 cells thick. The corresponding

inflamed synovial membrane consists of mainly macrophages and T lymphocytes (Feldmann

et. al., 1996). Macrophages in particular are the initiators of the pathogenic cascade of RA.

Within the synovial tissue, once macrophages are activated they are involved in recruitment

and activation of inflammatory cells, cell contact, overexpression of MHC class II molecules,

and cytokine production. Macrophages amplify this autoimmune disease by chronic

activation of monocytes and production of different cytokines (Kinne et. al., 2000).

The proinflammatory cytokines, TNF- and IL-1, are produced by activated

macrophages and fibroblasts in the synovial membrane and are believed to be pivotal

cytokines in the signal transduction of the inflammatory cascade. The TNF- response is

thought to come first, and IL-1 expression follows. A mutation in the promoter of TNF- and

IL-1, cause RA patients to suffer from an overproduction of these cytokines and cause

articular damage (Feldmann et. al., 1996 and Sebbag et. al., 1997) . From a study by

Sebbaget. al., they found that cytokine-stimulated T cells by TNF- , interacting with


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macrophages in the rheumatoid synovial membrane, contribute to the continuous and

excessive production of TNF- in the RA joint (1997). It is also suspected that IL-15 may

also play a role in inducing macrophage TNF- production in RA by the activation of T cells

(McInnes et. al., 1997). This constant stimulation and signal received to create TNF- and IL-

1 are what induce the chronic inflammation of the joints.

Furthermore, more extensive studies show that the cytokine IL-6 has also been found

in the synovial fluid during different phases of RA. IL-6 levels in the synovial fluid correlate

to the degree of joint damage of a RA patient and have been thought to promote the

generation of osteoclasts. Osteoclases are large multinucleated cells that differentiate from

macrophages and break down bone. This reaction may be what promotes excessive bone

deformation in the severe cases of the disease in the rise of macrophage activation and

fibroblasts in the RA synovial membrane (Kinne et. al., 2000).


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References

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Firestein, Gary S. Aug 2004. The T cell cometh: interplay between adaptive immunity and

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A. Rosen, C. Zhang, H.A. Mnard, Z.J. Zhou, T. Palosuo, W.J. Van Venrooij, R.L. Wilder,

J.H. Klippel, H.R. Schumacher, H.S. El-Gabalawy. 9 March 2000. Rheumatoid arthritis

associated autoantibodies in patients with synovitis of recent onset. Arthritis Research.

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Kinne, R.W., R. Brauer, B. Stuhlmuller, E. Palombo-Kinne, G.R. Burmester. 2000.

Macrophages in rheumatoid arthritis. Arthritis Research. 2:189-202.

Malattia, Luca. 2006. The impact of smoking and genes on rheumatoid arthritis. Arthritis &

Rheumatism.Accessed 11 December 2010.

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Martin, R.H. 1998. The role of nutrition and diet in rheumatoid arthritis.Proceedings of the

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Mayo Clinic Staff. 3 March 2006. Rheumatoid Arthritis.Mayo Foundation for Medical

Education and Research (MFMER).Accessed 11 December

2010.http://www.mayoclinic.com/health/rheumatoid-arthritis/DS00020.

McInnes, I.B., B.P. Leung, R.D. Sturrock, M. Field, F.Y. Liew. Feb 1997. Interleukin-15

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RA.com. 2006. RA In depth: An up-to-date understanding of Rheumatoid Arthritis. RA.com.

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Rheumatism.Accessed 11 December

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Schering-Plough Corporation. 23 March 2006. Remicade approved in Australia for treatment

of early rheumatoid arthritis and psoiatic arthritis. Medical News Today. Accessed 11

December 2010 .http://www.medicalnewstoday.com/medicalnews.php?newsid=40268.


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Sebbag, M. S.L. Parry, F.M. Brennan, M. Feldmann. March 1997. Cytokine stimulation of T

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Singh, Debashis. 9 Oct 2004. Merck withdraws arthritis drug worldwide. British Medical

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Svendsen, A.J., N.V. Holm, K. Kyvik, P.H. Petersen, P. Junker. 2 Feb 2002.Relative

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Warner, Jennifer. 9 June 2004. Vitamin C may fight rheumatoid arthritis. WebMD Medical

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Betamethasone is a kind of topical corticosteroids commonly prescribed for the treatment of skin and

scalp disorders such as arthritis, asthma, ulcerative colitis, severe psoriasis, itching, redness, dryness,

crusting, scaling, eczema, and inflammation.

Corticosteroids are anti-inflammatory medicines. Inflammation of the skin happens due to the irritation

of the skin, and is caused by the release of various substances that are important in the immune

system. These substances cause blood vessels to widen, resulting in the irritated area becoming red,

swollen, itchy and painful.

Betamethasone works by acting inside the skin cells to decrease the release of these inflammatory

substances.

pa tho genesis of rheumatoid arthritis

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