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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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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.