Vitamin D (vit D) is a fat-soluble prohormone that acts by binding to vitamin D receptor (VDR).1 The discovery of VDR in most of the cells of the immune system (lymphocytes and macrophages) suggests that it participates in the regulation of the immune response, beyond its traditional role in bone health and calcium homeostasis. Vitamin D has been related to several chronic diseases such as cardiovascular disease, cancer and autoimmune diseases like type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus (SLE).2,3 The latter is a multisystem autoimmune disease characterized by a diversity of immunological changes. A number of the immunomodulatory activities of vit D deficiency counteract the immunological alterations observed in SLE. This vitamin has been related to inhibition of the production of IgG anti-double-stranded DNA (anti-dsDNA), dendritic cell maturation and interferon alpha (IFN-α) gene expression in patients with SLE.4,5 A recent study also showed that patients with SLE and vit D deficiency had greater IFN-α activity and B-cell activation compared with those who had higher vit D levels. This fact shows that vit D insufficiency can intensify the immunological changes in SLE patients6; this deficiency seems to be multifactorial (lack of sun exposure, use of sunscreens, glucocorticoid therapy and chronic kidney disease).7,8 The epidemiology of vit D insufficiency in SLE patients in tropical countries like Mexico should be analyzed, as we have access to preventive and therapeutic methods. However, the relationship between vit D levels and disease activity is a controversial subject. The objectives of this study are to determine the prevalence of vit D insufficiency and deficiency in Mexican SLE patients and compare the vit D levels in patients with and without disease activity.

In this observational, cross-sectional, prospective study we enrolled Mexican Mestizo women who met the classification criteria for SLE of the American College of Rheumatology (ACR).9,10 The patients were from the research unit for systemic autoimmune diseases of Hospital General Regional N.° 36 of the Mexican Social Security Institute, Puebla, Mexico. All of the participants signed the informed consent form. The local institutional committee approved the study. The sample size was determined in accordance with the difference in vit D in SLE patients with and without disease activity. The calculated minimum sample size was 126patients. The participating women were legally of age (≥18 years), and were excluded if they had chronic kidney disease (creatinine clearance <60mL/min), cancer or hyperparathyroidism, and if they were pregnant or breastfeeding. A structured interview was held to obtain demographic data and the medical history, including age, a history of photosensitivity, the use of sunscreens, disease duration, a diagnosis of diabetes mellitus, glucocorticoid (prednisone) therapy and dose at the time of the study, as well as administration of immunosuppressive agents, chloroquine and vit D supplementation. Physical examination provided weight, height and body mass index.

The measurement of serum 25(OH)D levels is considered to be the most accurate method of evaluating an individual's vit D status.14 The results of the present study show that low vit D levels are common among patients with SLE (91.9% with levels <30ng/mL), despite the fact that the population studied lives in Mexico, a country with sunny weather most of the year. To our knowledge, this is the first Mexican study designed to identify the prevalence of vit D insufficiency and deficiency in a population with SLE. A number of studies in other populations have reported these prevalences in SLE, although the 25(OH)D levels considered for the analysis differ from one study to another (Table 3). In a recent report, Mok et al.15 studied 290 SLE patients, finding a prevalence similar to the 96% observed by us, one of the highest, together with that of a Spanish study authored by Cutillas-Marco et al.16 in which, in a population of 55 patients—most of whom (80%) had skin involvement—the authors found a prevalence of insufficiency of 95% and of deficiency of 11%. A Mexican report evaluated the vit D insufficiency in the general population, including 31 women, with a mean age of 34.1±9.7years. The prevalence of vit D insufficiency (<30ng/mL) in this group was 83.9%.17 Clark et al.18 measured serum vit D levels in 585 healthy Mexicans, 54% of whom were women; of the total population, 9.6% had adequate levels (≥30ng/mL), with prevalences of 46.8% and 43.6% for levels of 20–29ng/mL and <20ng/mL respectively. Both studies show a high prevalence of vit D insufficiency in the general population of Mexico. However, our study suggests that the frequency of vit D insufficiency is greater in SLE patients. On the other hand, in the present study, we analyzed the possible risk factors associated with vit D insufficiency in women with SLE, finding no association with age, disease duration, photosensitivity, photoprotection, vit D supplementation or glucocorticoid therapy. The absence of these associations may be due to a sample size that was insufficient for this purpose. With respect to these findings, it is important to point out that vit D plays two important physiological functions in SLE patients: first, it helps to preserve bone homeostasis, maintaining the amount of calcium-phosphate product within a normal range19 and, second, it also modulates the immune system and has immunoregulatory effects. In vitro studies have shown that 1,25-hydroxyvitamin D3 modulates the immune response, both innate and adaptive.20 Vitamin D increases the production of interleukin 10 and the chemokine, CCL22, derived from dendritic cells that promote the development and chemotaxis of T regulatory cells.21,22 It also decreases T lymphocyte activation mediated by dendritic cells through the downregulation of the expression of major histocompatibility complex class II molecules and costimulators.5 Moreover, vit D exerts modulatory effects on the B cells, inhibiting their proliferation, their differentiation into plasma cells and the production of immunoglobulin (Ig) G and IgM.23 Several of the immunoregulatory actions of vit D counteract the immunological changes observed in SLE patients. Studies have demonstrated that 1,25-hydroxyvitamin D and its analogs inhibit the production of IgG anti-dsDNA.24 Likewise, vit D has been found to inhibit dendritic cell maturation and the expression of IFN-α genes in patients with SLE.4 In a more recent study, it was also seen that SLE patients with vit D deficiency had a greater serum IFN-α activity and B cell activation compared with those patients who had higher levels of vit D.6

Considering the effects of vit D on immunological tolerance, there is growing interest in the influence of vit D deficiency on disease activity in SLE. It is evident that vit D could physiologically contribute to the regulation of the innate and adaptive immune responses. This concept is compatible with the results of research that takes into account the association between vit D insufficiency and a more marked activity in SLE; however the results are controversial. Ruiz-Irastorza et al.,25 analyzing 92 SLE patients in Spain, concluded that vit D insufficiency was not associated with activity measured with the SLEDAI score, as occurred in the study of Toloza et al.,26 who, in 124 SLE patients, observed no correlation between disease activity and the vit D levels. Souto et al.27 recently studied 159 Brazilian patients with a diagnosis of SLE, and found no association between the score for lupus activity evaluated by SLEDAI-2K and vit D insufficiency. In our study, we failed to find an association between vit D insufficiency and lupus activity measured using the MEX-SLEDAI tool; however, it is important that we consider that most of our patients had mild-to-moderate activity, meaning that these results could not be extrapolated to populations with SLE in whom the disease activity was severe. On the other hand, Amital et al.28 analyzed several cohorts of 378 SLE patients from Israel and Europe, and concluded that the serum vit D concentrations were inversely related to disease activity; however, this correlation was weak (r=−0.12). In a study in Hungary, in which 90 SLE patients were analyzed, the serum 25(OH)D levels correlated inversely with the SLEDAI score, and with the concentrations of anti-dsDNA, of anti-Smith and of immunoglobulins.29 The present study has certain limitations. In the first place, the cross-sectional nature of the study design, with the possible presentation of susceptibility bias. In the second place, the absence of healthy controls with whom to compare prevalences of vit D insufficiency and deficiency. Moreover, in our study, it was not possible to determine anti-dsDNA, C3, C4 or other serum markers in all of the patients. Finally, as we mentioned above, most of the participants in our study had a lupus activity that had been classified as mild-to-moderate, a situation that limits the extrapolation of our results to other SLE populations.

In conclusion, women in whom SLE has been diagnosed have an elevated prevalence of vit D insufficiency, even in a tropical country like Mexico. The prevalence of vit D insufficiency shown by our findings was higher than that of most of the studies conducted in a population with SLE. In this report, it was not possible to identify factors associated with vit D insufficiency, and the 25(OH)D levels were not related to the disease activity. The consequences of vitamin insufficiency can interfere with bone metabolism, but may have no relationship to the lupus activity.

The authors declare they have no conflicts of interest.