Rheumatoid arthritis (RA) is the most common inflammatory joint disease, affecting 0.5% –1% of the world population. Increasing evidence shows that therapeutic intervention early in the course of RA results in more efficient disease control, less joint damage and better prognosis of disease outcome. Rheumatoid factor (RF), the first autoantibody correlated with RA, is directed at the Fc region of IgG and is usually IgM isotype. It is the commonly accepted and widely used serologic test for RA; however, it is not specific in diagnosing early RA because it may be present in healthy elderly persons or in patients with other autoimmune and infectious diseases [12
Anti-CCP is considerable motivation to accurately diagnose RA in patients with inflammatory arthritis early in the course of disease. It was significantly associated with some parameters of both disease activity and severity [13
]. Anti-CCP assays are effective and widely used for diagnosing RA, however, their sensitivity is limited in patients with early RA [14
]. CCP is not expressed in the synovium, and citrullinated proteins expressed in the rheumatoid joint would probably be more relevant as targets of auto-antibodies used to diagnose RA. Citrullinated vimentin is present in synovial membranes and is released in increased amounts in response to growth factors and pro inflammatory cytokines, suggesting its involvement in the pathophysiology of RA [15
The present study focuses on the level of anti-MCV in patients with early RA. In addition, sensitivity and specificity of the anti-MCV test were determined in patients with RA. This study included 75 subjects; 45 patients diagnosed as RA, 15 patients complain from osteoarthritis and 15 apparently healthy persons as control group. Our results showed significant difference in the age between the OA, RA patients and the control group (P value<0.001), also, our study showed that RA are more likely to occur between middle and old age. This result was in agreement with the results of Elbordeny et al., [16
], El-barbary et al., [17
] and Abdul Wahab et al., [18
] who reported similar results regarding earlier onset of RA and that OA increases progressively with age at all joint sites.
There was no difference regarding patients sex in RA and OA groups as both prevail mainly in female patients (82.2% and 93.3%), this can be attributed to changes in sex hormone levels which may play a role in the development of RA and OA [19
]. Studies conducted by several investigators reported similar results as current study in term of RA is mainly affecting middle age group and female is the predominant gender [21
In the preset study, RF was mainly positive in patients with RA (57.8%), while in all OA patients RF was negative. This result was in agreement with the result of Shukaili et al., [1
] who found that 59% of RA patients were positive for RF.
The levels of anti-MCV and anti-CCP were significantly higher in RA patients when compared with their levels in OA and control groups (P value<0.001). This was in agreement with the results of Abou el-Fetouh and Abo zaid, [23
]. This can be explained by the hypothesis that vimentin might trigger the initial immune response in RA [24
]. It activates T lymphocytes by binding to HLA-DR4 on the surface of antigen presenting cells and may contribute to certain pathways in the pathogenesis of RA. Several studies demonstrated significant elevation in serum anti-MCV in RA patients versus controls [25
Nugraha et al., [26
] showed that values of anti-MCV can be used for diagnosing rheumatoid arthritis in anti-CCP-negative patients. So anti-MCV is superior in comparison to anti-CCP.
In our study, specificity of anti-MCV at the cutoff value of 20.2 U/ml was 48.2%. Then we compared sensitivity at values of 24.2 U/ml and 27.5 U/ml respectively and we found these values has advantages on sensitivity and NPV, while the latter was slightly better on specificity (93.3%) and PPV (97.8%) (high specificity means that a positive result markedly increases the probability that the patient will have RA). That is why the best cutoff value was obtained at the level of 27.5 U/ml and the Area Under the Curve (AUC) was 0.997. These results were in agreement with the result of Rulin et al., [27
] who found the specificity at the cutoff value of 20 U/ml was only 45.6%. The cutoff value of 30 U/ml has advantages on sensitivity (78.2%) and NPV (77.4%) while specificity was 93.4% and PPV 93.7%. Moreover, the best Youden’s index was obtained at the cutoff value of 30 U/ml. Nugraha et al., [26
] have revealed that anti-MCV has good specificity of more than 93.75% in rheumatoid arthritis. Anti-MCV is produced earlier than anti-CCP in the course of the synovial and joint damage.
In the current study, significant positive correlation was found between anti-MCV and anti-CCP in patients with RA (P value<0.001). This was in agreement with study of Khalifa et al., [7
] who reported same significant correlations between anti-CCP and anti-MCV antibodies. This was explained by what is documented by Engelmann et al., [28
]; the cross-reactivity experiments between anti-MCV and anti-CCP antibodies indicate that anti-MCV and anti-CCP target some shared epitopes which may explain the high positive correlation between these antibodies. Several studies by Mutlu et al., [29
] and El Shazly et al., [30
] reported same high significant positive correlations between anti-MCV levels and anti-CCP. Other studies reported a strong correlations between levels of anti-MCV and clinical parameters (number of swollen joint, disease activity and DAS-28) making anti-MCV a better prognostic marker for future radiographic changes [31
In RA patients, there was significant positive correlation between RF and anti-CCP (P value=0.004) this result was in agreement with the result of Abdul Wahab et al., [18
] who found that anti-CCP is positively correlated with RF (P<0.001) and in agreement with the result of Greiner et al., [34
] who found weak but significant linear correlation between anti-CCP and RF (r=0.2, P=0.03).
In the present study, no significant correlation was found between RF and anti-MCV (P value=0.413). This was in contrary with, Al-Shukaili et al., [1
] who reported significant positive correlation between Anti-MCV and RF (P value=0.040). This may be due to difference in the methods used in both studies. CRP results were positive in only 35.6% of RA group. This result was in accordance with Al-Shukaili et al., [1
] who found only 16% of RA patients are positive for CRP.
Significant positive correlation was found between anti-MCV and 1st hour ESR (P value<0.001) in RA group. This was in agreement with Ursum et al., [5
] who reported that anti-MCV antibodies are correlated with disease activity parameters such as erythrocyte sedimentation rate and serum C-reactive protein, also, there were significant positive correlations between levels of anti-CCP antibodies, CRP and ESR in RA patients ( P value=0.010 and<0.001) respectively.
In conclusion, our results for anti-MCV antibodies were comparable with other reported results in RA patients. Generally, anti-MCV antibodies appear to be a very useful diagnostic test for RA. Anti-MCV is a good marker for early diagnosis of RA with higher sensitivity and specificity when compared to other markers. The use of Anti-MCV and Anti-CCP collectively give the best result for the diagnosis of rheumatoid disease.