Standard treatment for rheumatoid arthritis (RA)—methotrexate and glucocorticoids—successfully improves clinical symptoms for most patients. Research by Ilaria Buondonno, PhD, and colleagues at the University of Torino, Italy, has revealed that the combination of a single dose of cholecalcipherol (300,000 IU) with standard treatment may go even further to improve the general health of patients with RA at three months relative to patients receiving standard therapy alone. The investigators published the results of their research, which evaluated patients at the very beginning of RA disease, online June 5 in PLoS One. Their intention was to investigate the early immunological alterations in patients with RA.1
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The study included patients and control subjects who were matched for age, post-menopausal period and body mass index. However, the two groups did differ with regard to levels of 25-OH vitamin D, with patients being significantly lower than controls (16 ± 2.1 vs. 26 ± 2.23). The study, thus, confirms findings from previous research that concluded that RA is associated with lower levels of 25-OH vitamin D.
The investigators also observed that patients with early RA had a significant imbalance in T CD4+ subtypes, as well as increased levels of non-classical osteoclast precursors and pro-inflammatory cytokines. In particular, patients with early RA had an increase in the number of CD4+/IFNγ+, CD4+/IL4+, CD4+/IL17A+ and CD4+/IL17A+/IFNγ+ cells. However, the researchers did not find a significant imbalance in regulatory T cells. Previous research has also demonstrated that non-classical osteoclast precursors correlate with the grade of inflammation and the severity of disease. The researchers, thus, hypothesized that their observed increase in non-classical osteoclast precursor cells may be reflective of the bone damage seen in patients with RA.
The team found that patients with early RA had increased levels of RANKL, TNFα, TGFβ, IL-23 and IL-6 relative to controls. These results are similar to previous reports that have found increased levels of RANKL, TNFα and IL-6 in the early phase of RA. Additionally, TGFβ1 is known to modulate anti-inflammatory and immunosuppressive responses, and this study is the first to evaluate levels of TGFβ in the early RA phase vs. RA patients in general. The results are consistent with the hypothesis that TGFβ1 may have a compensatory effect in response to the increased inflammatory state in patients with early RA.
The researchers also noted that IL-23 is required for the amplification and stabilization of CD4+/IL17A+ cells. Thus, the documented increase in levels of IL-23 may explain the increased formation of CD4+/IL17A+ cells. In contrast, however, levels of IL-17 and IFNɣ were not significantly different between patients and controls.
The investigators then evaluated the effects of vitamin D treatment on clinical signs and symptoms of early RA in 18 patients per group (standard treatment with or without cholecalcipherol). As expected, they found that standard treatment significantly reduced Disease Activity Score 28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and Visual Analog Scale for Pain (VAS pain). Although standard treatment had no effect on T helper subset, osteoclast precursor cells or the majority of clinical signs and symptoms, it did reduce levels of IL-23. Adjunctive treatment with vitamin D had the added benefit of improving global health, relative to standard therapy alone, as evaluated on a numeric scale.
Lara C. Pullen, PhD, is a medical writer based in the Chicago area.
- Buondonno I, Rovera G, Sassi F1, et al. Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind placebo-controlled study. PLoS One. 2017 Jun 5;12(6):e0178463. doi: 10.1371/journal.pone.0178463. eCollection 2017.