VICTORIA, B.C. – Suboptimal vitamin D levels may play a role in the pathogenesis of inflammatory arthritis but not in its subsequent clinical course, judging from the findings of a study involving 264 adult patients with early disease.
Fully 77% of patients had vitamin D deficiency or insufficiency at baseline, reported lead investigator Dr. Carol A. Hitchon at the annual meeting of Canadian Rheumatology Association. But in findings that contrasted those of some earlier studies, levels were not significantly associated with disease activity at that time or with achievement of remission 1 year later.
Dr. Carol A. Hitchon
The study also found that vitamin D levels did not correlate with levels of immunoglobulin directed against common pathogens implicated in the development of rheumatoid arthritis.
"It’s possible that vitamin D levels may not be that important in terms of clinical activity and that vitamin D status may be more important in predisposing to rheumatoid arthritis," Dr. Hitchon commented. "I don’t think vitamin D is the only answer. And I think it’s not just the level, it is probably other elements of the vitamin D pathway that might be important, in terms of how they may regulate autoimmune processes."
A session attendee wondered whether patients with inflammatory arthritis may simply have lower levels of this vitamin because they go out in the sun less.
That is a possible explanation, acknowledged Dr. Hitchon of the arthritis center at the University of Manitoba in Winnipeg. "We are hoping to measure vitamin D levels in a population that generally has more sun exposure based on where they reside, and that may give us some correlation," she added.
Accumulating data suggest that vitamin D plays a role in maintaining both tolerance and immunity to pathogens. Thus, the investigators hypothesized, "if you are deficient in vitamin D, it may lead to a break of self-tolerance and the development of autoimmunity. Similarly, deficient vitamin D can impair or alter the initial response to pathogens, leading to increased microbial load, which can also increase or affect autoimmunity," Dr. Hitchon said.
She and her colleagues studied patients from the Manitoba Early Arthritis Cohort. All of the patients had had symptoms of inflammatory arthritis for no more than 1 year, and had at least one swollen joint.
The severity of their arthritis was assessed with the DAS28-CRP (28-joint count Disease Activity Score, C-reactive protein). Circulating levels of 25-hydroxyvitamin D and antibodies to Escherichia coli and Proteus mirabilis – both of which have been implicated in rheumatoid arthritis – were measured in serum collected before the start of treatment.
The average age of the patients studied was 48 years, and 76% were women. Overall, 60% were rheumatoid factor–positive, and 49% were positive for CCP2 (cyclic citrullinated peptide, second-generation assay). Their mean DAS28-CRP score was 3.99.
Results showed that 16% of patients had vitamin D deficiency and 61% had vitamin D insufficiency, while just 23% had optimal levels. Smokers had significantly lower levels than did nonsmokers.
There was no association at baseline between vitamin D levels and rheumatoid factor or CCP2 levels, DAS28-CRP score, or several other measures of disease activity, reported Dr. Hitchon, who disclosed no relevant conflicts of interest.
In adjusted analyses, vitamin D levels were not significantly associated with DAS28-CRP score at baseline or with achievement of remission 1 year later. "As has been previously shown, the major predictor of 1-year outcome was the baseline DAS score," she noted.
During the study, 20% of patients had an improvement in their vitamin D levels, moving to a higher category, whereas 12% of patients had a worsening, moving to a lower category. "This is without any formal protocol or plan to supplement vitamin D," Dr. Hitchon pointed out.
There was also no significant correlation between vitamin D levels and levels of immunoglobulins –whether IgA, IgM, or IgG – to E. coli or P. mirabilis.
Dr. Hitchon disclosed no relevant conflicts of interest.