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April 26, 2014 RHEUMATOID ARTHRITIS
Abstract:
Background: Rheumatoid arthritis (RA) is an auto immune disease that result in chronic, systemic inflammatory disease that may affect tissues and organs , and especially synovial joint that is maybe result from an interaction between genetic factors and environmental factors.
Epstein-Barr virus EBV is associated with several autoimmune diseases, such as systemic lupus erythematosus, Rheumatoid arthritis and multiple sclerosis.
Objective: To study the relationship between Epstein-Barr virus (EBV) and Rheumatoid arthritis
(RA).
Patient and method: The study was carried out in the period between January 2014 and March
2014.the study involved 86 patient diagnosed with RA and 40 healthy individuals as control group. Serum samples were collected to investigate the level of EBV-IgG by using ELISA technique.
Result: This study showed that 90% of rheumatoid arthritis had positive EBV-IGG while only
25% of healthy individual had positive EBV- IgG. The mean values of EBV- IgG were significantly higher among RA patient ( 0.578IU/ml) in comparison with that in control group ( 0.225IU/ml ).
Conclusion: The serum level of EBV-IgG significantly higher in RA patient in contract with those in healthy individuals.
Keywords: Epstein-Barr virus, Rheumatoid arthritis, EBV-IgG , ELISA

Introduction:
Rheumatoid arthritis (RA) is a chronic inflammatory poly arthritis that progressively destroys synovial joint and can cause systemic complication. And the rheumatoid arthritis affect about
1% of the world population {1} and it is highly prevalence in women more than men {2,3}.
EBV is the virus of the herpes family that causes acute infectious mononucleosis and various lymph proliferative diseases such as lymphoma and nasopharyngeal carcinoma.
EBV infection is very common and in the United states.
By the age of 40 up to 95% of the population is likely to come across this virus {4} .
EBV was first associated with auto immune disease in 1971 when a high pre valance of the virus was found in the sera of systemic lupus erthymatosus (SLE ) {5} patient over the years .This relationship was strongly established and today it is known that EBV infection preceding the development of auto immune disease
And today EBV infection is currently associated with multiple chronic auto immune disease such as rheumatoid arthritis {6}.
A viral trigger of RA in the genetically predisposed has been
Hypothesized for many years{7,8}.
A virus could act as an adjuvant in the development of autoimmunity, non-specifically stimulating innate immune responses, including mast cells,dendritic cells, Toll-like receptors and complement receptors{9}.
Poly arthritis resembling RA is seen clinically soon after exposure to multiple viruses including rubella, human T cell leukemia virus-1 (HTLV-1), parvovirus B19, and hepatitis B and C {8,10,11}.
Exposure to a common virus would explain the ubiquity of RA worldwide. However, such a virus has eluded identification by modern techniques possibly because of a long latency period, with RA onset years after initial exposure.
Viruses including Epstein–Barr virus (EBV), parvovirusB19, HTLV-1, human herpesvirus-6, human herpesvirus-8, and human endogenous retroviruses-5 have all been proposed to be involved in the pathogenesis of RA {12,13,14} .
However, most of the evidence implicating viruses in the pathogenesis of RA is circumstantial and inconclusive.
Tantalizing observations have often been based on in vitro or animal studies, case reports, or studies with small sample sizes, cross-sectional designs, or no control groups.

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April 26, 2014 RHEUMATOID ARTHRITIS
Material and method:
After the study was approved by the ethical committee of the microbiology department .the study involved 86 patient diagnosed with rheumatoid arthritis attending rheumatology clinic in
ALKHARTOUM teaching hospital and 40 healthy individual as a control group.
Blood samples were obtained from each individual by venous puncture then were left to clot at room temperature, centrifuged and serum was collected. EBV-IgG was detected with commercially available enzyme immune sorbent assay kits (ELISA) test for detection of IgG antibodies to Epstein-Barr virus in human serum.
Analyzing:
The data retrieved from the questionnaires were analyzing using the statistical package for social science and Microsoft Excel.
RESULT:
A total of 86 patients with rheumatoid arthritis were studied about 78 of patients positive for
VCA IGG and 8 patients sample negative to it. And total of 40 healthy individual about 10 positive for VCA-IgG and 30 negative for VCA-IgG.
RA patient
Control group n positive Percent negative
86
40
78
10
90.7%
25%
8
30
Percent
9.3%
75%
Discussion:
On this paper we analyzed by ELIZA fourth generation, the hypothesis of an association of EBV, with RA.
This study of antibody responses to EBV in rheumatoid arthritis has demonstrated several interesting features.

The frequencies of anti-VCA in RA and the virus were concerned; RA patients did not appear to have different exposure experiences. However,
A higher percentage of RA patients had elevated titers of anti-VCA.
In the early seroepidemiological studies of antibodies to EBV antigens, it was rapidly noted that
EBV was a ubiquitous virus and that antibodies to VCA were be present in significantly higher frequencies in the EBV-related diseases, infectious mononucleosis, Burkett’s lymphoma, and nasopharyngeal carcinoma,(15). Anti-VCA titers have also been shown to be elevated, albeit inconsistently (15), in several other diseases including lymphomas, and systemic lupus erthymatosus.
Despite the higher anti-VCA titers in the RA patients observed here as well as in the diseases just noted, investigators such as Henle (15) have emphasized the need to obtain .
Conclusion:
There is large body evidence indicating that EBV infection has a major role in the pathogenesis of organ specific and non organ specific human chronic auto immune disease .this evidence includes: a high frequency and high levels of circulating anti-EBV antibody. triggering first attack autoimmune disease by infectious mononucleosis due to primary EBV infection; an increase frequency of circulating EBV – infected B cell; defective T-cell control of EBV infected B cell an increase level of EBV DNA in target tissues; monoclonal B-cell expansion in the target organs; and increased risk of developing B-cell lymphoma in the target organ of chronic autoimmune disease; and T-cell and antibody cross-reactivity between EBV antigens and self antigen. this finding can be explained by the hypothesis that chronic autoimmune diseases occur in individual genetically susceptible to the effects of B-cell by EBV resulting in an increased frequency of latently EBV- infected auto reactive B-cell. EBV infected auto reactive B-cell could produce pathogenic auto antibodies ; they could also act as professional antigen- presenting cell in the target organ were they could provide of a co stimulatory survival signal to auto reactive T-cell that have been activated in peripheral lymphoid organs by cross -reactivity with infectious agent and that would otherwise undergo activation induced apoptosis in the target organ. on receiving acostimulatory survival signal from the EBV infected B cell ,the auto reactive
T cell could proliferate and produce cytokines , which recruit other inflammatory cells , with resultant target organ damage and chronic autoimmune disease like (RA).
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