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the levels of 25OHD associated with SLE. Kamen et al. (2006), in a small subset of a larger population-based cohort, found that 22 out of 123 SLE patients across race, age, and gender groups had 25OHD levels below 25 nmol/L and that African Americans had levels significantly lower than whites (40 nmol/L compared with 78 nmol/L [p = 0.04]). In a small pilot study of 50 subjects (25 per group), Huisman et al. (2001) found that 50 percent of female SLE patients had 25OHD levels below 50 nmol/L. The associations between vitamin D status and incidence of SLE identified in these studies are not borne out by evidence from a prospective cohort study of dietary factors and risk for developing SLE. An analysis of a small subset of women participating in NHS over a period of 22 years found no association between vitamin D (or calcium) intake assessed with a food frequency questionnaire and risk for developing SLE or RA (Costenbader et al., 2008). In a cross–sectional survey, Ruiz-Irastorza et al. (2008) found that 75 percent of patients with SLE had serum 25OHD levels below 75 nmol/L and 15 percent had levels below 25 nmol/L, and 25OHD levels in blood in patients with SLE were not responsive to calcium and vitamin D treatment. Thus, it is not clear whether therapeutic treatment would have any effect on disease manifestation. The few relevant studies identified for review, and the lack of uniformly significant findings between studies, which may be a result of the small study populations (< 200 participants), are not sufficient to permit the committee to draw a conclusion about an association between SLE and vitamin D intake or 25OHD levels in blood.

Infectious Diseases

Tuberculosis Pulmonary tuberculosis (TB) is a granulomatous infection in which hypercalcemia occurs in a subset of patients (Sharma et al., 1972; Abbasi et al., 1979; Need and Phillips, 1979). The increased production of immune and inflammatory cells in patients with TB correlates with increased serum levels of calcitriol (Adams et al., 1989) and with calcitriol in pleural fluid (Cadranel et al., 1994). Treatment of alveolar macrophages with IFN-γ appears to stimulate synthesis of calcitriol (Koeffler et al., 1985; Reichel et al., 1987). Although vitamin D has been used as a therapeutic agent in the management of TB (Martineau et al., 2007a), treatment of individuals with active TB with supplemental vitamin D exacerbates or reveals hypercalcemia (Sharma, 1981).

Biological plausibility Vitamin D may be an important factor in innate immunity in the upper respiratory tract (reviewed in Bartley, 2010). Although calcitriol does not have direct anti-bacterial activity, it induces anti-tubercular actions in cultured monocytes and macrophages (Chan et al., 1994). Recent evidence, stemming from the molecular cloning of 1α-hydroxylase (Monkawa et al., 2000), supports macrophages as the source



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