Hypovitaminosis D has been associated to autoimmune disease including RA in various studies [6]. Moreover, it was considered as a prognostic and reflective factor of disease activity. Anti-CCP and RF, on the other hand, were confirmed as diagnostic and also prognostic serum markers in RA patients. Therefore, the correlation between RA and vitamin D as well as its relationship with the mentioned autoantibodies separately prompted us to investigate if there is any significant correlation between the RA-related autoantibodies and 25(OH)D. Interestingly, we found no substantial association between Hypovitaminosis D and the foregoing serum markers. Thus, the lack of an appropriate amount of vit. D may not affect autoantibodies-dependent prognosis.
In this study, 73% of our sample population were classified as vit. D deficient. Haque et al. reported a favorable result which was 63%. Therefore, the levels below optimal vit. D can be considered as a predisposing factor in developing RA features in susceptible patients, and routine administration of vit. D as a cheap and safe supplement should be well-thought-out. Rennie et al. also recommended that vit. D supplement intake reduces the severity of RA symptoms.
This study showed no significant relationship between DAS28 score and vit. D levels which indicate the disease activity VAS score; in other words, the number of swollen and tender joints, inflammatory blood markers (e.g., ESR and CRP) and patient’s assessment of healthiness as well as pain self-assessment were not dependent on vit. D metabolites level.
Several experiments have shown that there is no correlation between the level of 25(OH)D and the activity of the disease [21]. Findings suggesting an opposite correlation between vitamin D metabolite levels and disease activity are contentious [22,23]. In a cross-sectional sample of 206 patients, Patel et al. found that each 10-ng / ml rise in the 25(OH)D level was correlated with a 0.3 decrease in the DAS28 score [24]. Despite lack of general association between vitamin D levels and DAS28, Higgins et al. claimed that, in the presence of vitamin D deficiency, patients could view themselves or be viewed by assessors as having reacted poorly to disease adjustment. He also offered evidence that the VAS factor is inversely linked to vitamin D, measuring the patient's understanding of symptoms, with lower levels delivering higher VAS values [25].
Based on our findings, we detected an inverse relationship between RA disease duration and vit. D levels. Chandrashekara et al. reported in a parallel study that patients with vit D deficiency had a prolonged duration of disease [26], while Haque et al. and Higgins et al. did not find any relationship between the disease duration and vit. D metabolites [23,25]. Lower levels of 25(OH)D over time may be related to functional and physical disability in RA patients followed by low exposure to sunlight and, therefore, a decrease in the level of vit. D metabolites. Patients with a greater period of sickness could also have had a worse diet or reduced exposure to sunshine.
In this report, we also revealed no significant correlation of vit. D metabolites level with inflammatory factors including CRP. Conversely, Kerr, et al. polemically, introduced the anti-CCP antibody positivity and higher CRP concentrations, as the associated factor for the higher risk of vit. D deficiency [27]. Every 10-ng / ml improvement in the 25(OH)D level was correlated with a 25 percent reduction in the CRP level, as reported by Patel et al. [24] In a similar study among 55 patients with RA, serum 25(OH)D levels were significantly negatively correlated with CRP levels [28]. Furthermore, Chandrashekar et al. found a significant improvement in CRP levels following vit. D supplement consumption [26]. Nevertheless, there are controversial results on investigating the relationship between 25(OH)D and some inflammatory serum factors; further evaluation of RA patients considering various stages should be performed.
There are few studies that assess the relationship of plasma 25(OH)D levels with autoantibodies which are related to RA such as anti-CCP and RF in patients diagnosed with RA. We found no association between vit. D levels with anti-CCP and RF, regardless of the severity and duration of disease. Feser et al. also indicated the absence of a substantial relationship between vit. D metabolites level and the mentioned autoantibodies which are in accordance with our results [29] Anaparti et al. and Yanan et al. described an inverse relationship between vit. D and anti-CCP [30,31]. Controversially, Herly et al. declared a significant positive association between vit. D and anti-CCP. [32] A positive association was also reported by Anaparti et al. between RF and vit. D levels [30]. It seems that vit D deficiency does not affect the higher titer of RA autoantibodies, but further studies with larger samples are required to confirm this result.
Many studies have focused on the association of vit. D and demographic variables; however, in our study, no significant correlation was obtained between vit D levels and variables including age, gender, and living location. Haque et al. confirmed the lack of correlation between sex and vit. D levels [23]. Whereas there are several studies which proved significant differences in vitamin D levels concerning gender. The difference in 25(OH)D levels according to gender was attributed to sex-related hormones [33,34]. Other studies also did not report any significant correlation as per age [35,23]. Furthermore, there was no defined relationship between hypovitaminosis D and living location [36]. Further studies with larger sample size are needed to assess the mentioned variable
It has been shown that there is an inverse association between vit. D level and educational status. On this account, the higher the educational level, the lower the vit. D level. Forrest et al. and Patel et al. also confirmed the negative correlation of the vit D level with educational status, as a marker of low socioeconomic status [37,24]. Lower socioeconomic status can also impact food choices among a minority of the populations and subsequently result in choosing less vit D rich foods such as fish. It is suggested that informing the society can reduce the incidence of vit. D deficiency.
There were some limitations in our study. It is possible that patients with longer disease duration had a worse diet or less sunlight exposure, so lower levels of 25(OH)D are reported by them. The second limitation was difficulty to precisely explain the causal relationships due to the fact that the study was cross-sectional.
As a conclusion, Vitamin D associated metabolites levels do not seem to be associated with the existence of RA-related autoantibodies such as RF and Anti CCP in RA patients. Furthermore, no significant correlation between serum inflammatory markers including CRP and vit D levels was found. Although there are no definitive results determining the exact ratio of 25(OH)D to disease activity or RA-related serum markers, evidence was found about the association of 25(OH)D and disease duration. Considering the levels below normal of 25(OH)D in a large number of cases (73%), 25(OH)D should be checked in those patients.