Background: Vitamin D deficiency is associated with cancer and autoimmune diseases, but little is known about the association between vitamin D and antinuclear antibodies (ANA), a biomarker of immune dysfunction in healthy populations. 0000185196 00000 n The https:// ensures that you are connecting to the Twenty-three per cent of vitamin D-deficient patients versus 20% of non-deficient patients were receiving treatment with azathioprine (p=1.000), 77% versus 60% were taking hydroxychloroquine (p=0.407), 23% versus 10% were receiving mycophenolate mofetil (p=0.637) and 23% versus 10% were being treated with methotrexate (p=0.637) (Fisher exact test). Competing interests JBH has served as a consultant for BioRad and owns stock in IVAX Diagnostics. CCL-25, American Type Culture Collection, Manassas, Virginia, USA) were cultured with 50% patient serum for 6 h and then lysed. Meier, Dale P. Sandler, Eleanor M. Simonsick, Christine G. Parks; Association between Vitamin D Deficiency and Antinuclear Antibodies in Middle-Aged and Older U.S. ANA fluorescence intensities of 3 or 4 were classified as seropositive for ANA, and intensities of 0 to 2 were classified as seronegative, consistent with previous studies in NHANES (14). Toubi E, Shoenfeld Y. Methods: A cross-sectional analysis using the National Health and Nutrition Examination Survey (NHANES) 20012004 was conducted. 0000069054 00000 n 0000021987 00000 n 2011 Sep; 70(9): 15691574. 25(OH)D levels were measured in 32 European American female patients with SLE and in 32 healthy matched controls. This study has several strengths. ANA was not associated with age, education, race/ethnicity, BMI, or NHANES cycle. The SLE patient group had a median 25(OH)D level of 17.3 (IQR 11.921.2) ng/ml (figure 1A). These results are consistent with growing evidence that vitamin D plays a role in modulating immune function, in addition to regulating cellular processes important in cancer cell growth and differentiation (23), and may contribute to the development of autoimmunity as measured by antinuclear autoantibodies, a potential marker of immune dysfunction. Hormonal, environmental, and infectious risk factors for developing systemic lupus erythematosus. PMC legacy view Ruiz-Irastorza G, Egurbide MV, Olivares N, et al. The reporter cell assay for serum IFN activity has previously been described in detail.31 Briefly, reporter cells were used to measure the ability of patient serum to upregulate IFN-induced gene expression. Cutolo M, Otsa K. Review: vitamin D, immunity and lupus. Those with severe vitamin D deficiency had 2.99 (95% CI, 1.257.15) times the adjusted odds of ANA than those with vitamin D levels in the normal range. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. 0000005447 00000 n Pearson correlation was done to assess the relationship between pERK1/2 and 25(OH)D values. We also showed evidence of a relationship between vitamin D levels in patients with SLE and the magnitude of B lymphocyte activation in PBMCs, as determined by pERK1/2 levels. 0000002741 00000 n 1Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA, 2Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA, 3Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA, 4Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA, 5Division of Rheumatology, Cincinnati Children's Hospital Medical Center and US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA. 0000007249 00000 n endstream endobj 442 0 obj <> endobj 443 0 obj <>stream Potential confounders were selected on the basis of a priori hypotheses or if they were associated with the exposure and outcome. 0000006525 00000 n Search for other works by this author on: National Institute of Environmental Health Sciences. Vitamin D and colorectal, breast, and prostate cancers: a review of the epidemiological evidence, Vitamin D and prevention of colorectal adenoma: a meta-analysis, Circulating 25-hydroxyvitamin D and prostate cancer survival, Circulating 25-hydroxyvitamin D serum concentration and total cancer incidence and mortality: a systematic review and meta-analysis, Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications, Vitamin D, steroid hormones, and autoimmunity, Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus, Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study, Harnessing the immune response for cancer detection, Serologic autoantibodies as diagnostic cancer biomarkersa review, Blood autoantibodies against tumor-associated antigens as biomarkers in early detection of colorectal cancer, Development of autoantibodies before the clinical onset of systemic lupus erythematosus, Natural autoantibodies in the serum of healthy womena five-year follow-up, Prevalence and sociodemographic correlates of antinuclear antibodies in the United States, Vitamin D levels are associated with expression of SLE, but not flare frequency, Association of low vitamin D with high disease activity in an Australian systemic lupus erythematosus cohort, Vitamin D deficiency and its association with disease activity in new cases of systemic lupus erythematosus, Vitamin D and breast cancer: inhibition of estrogen synthesis and signaling, 25-Hydroxyvitamin D laboratory procedure manual NHANES 20012002, 25-Hydroxyvitamin D laboratory procedure manual NHANES 20032004, Centers for Disease Control and Prevention, National Health and Nutrition Examination Survey 20012002 Data Documentation, Codebook, and Frequencies - Vitamin D, Demographic differences and trends of vitamin D insufficiency in the US population, 19882004, Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects, The cytokine milieu in the interplay of pathogenic Th1/Th17 cells and regulatory T cells in autoimmune disease, Reproductive and hormonal risk factors for antinuclear antibodies (ANA) in a representative sample of U.S. women, Autoimmunity and geriatrics: clinical significance of autoimmune manifestations in the elderly, Aging decreases the capacity of human skin to produce vitamin D3, This site uses cookies. 0000138417 00000 n The best fitting single-predictor model was compared with a model with both 25(OH)D and number of autoantibody specificities as predictors using the likelihood ratio test, and the fit was significantly improved with the two-predictor model (2 =3.931, p=0.047). 0000015491 00000 n However, in a logistic regression model with vitamin D status as the outcome and ANA positivity and age as the predictors, age did not predict vitamin D status (p=0.331) while ANA positivity remained a significant predictor (p=0.025). Anti-Ro, anti-dsDNA and anti-nRNP have each been shown to be independently associated with high serum IFN activity and, in addition, have been shown to influence serum IFN activity additively.32,33 We therefore analysed the number of lupus-associated autoantibody specificities present in patients with high and low IFN activity. 0000249947 00000 n 44 +!"\A}BZX+kcX{kbV=ZX+kcX{nTSQ"LE }Fg }Fg }Fg }Fg }Fg }Fg)EFTgSx*O3xTg{219`!2/gEH3"}F_}>/gEHQk"k"_>}qDo)|~?iwm}ne:-ig;7e )0\2 about navigating our updated article layout. 0000017609 00000 n The study sample was drawn from data collected by NHANES, a population-based, probability survey of the civilian, noninstitutionalized U.S. population (National Center for Health Statistics, Centers for Disease Control and Prevention). This was accomplished using MDDCs from patients with SLE as well as MDDCs generated from controls which had been incubated with plasma from patients with SLE.24,25. Bethesda, MD 20894, Web Policies Vitamin D modulates innate and adaptive immune responses, and vitamin D deficiency, which is common in older adults, has been associated with a variety of autoimmune diseases (58). Increased serum interferon (IFN) activity is associated with vitamin D deficiency and increased number of autoantibody specificities. Correspondence to: Judith A James, Arthritis and Clinical Immunology, Oklahoma, Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA; The publisher's final edited version of this article is available at. 0000227385 00000 n We thank Drs. Fourteen of the controls were determined to be ANA-positive. Specifically, vitamin D influences the efficiency of regulatory T lymphocytes and activity of T helper lymphocytes (Th17), both thought to be important for mediating and regulating autoimmune responses (6, 24). To determine whether the relationship between 25(OH)D and IFN activity was dependent on the number of autoantibody specificities, various statistical models were compared using logistic regression. Patients with SLE who had high IFN activity (>1 SD above the mean of healthy controls) had an increased number of lupus-associated autoantibody specificities compared with those who had low IFN activity (<1 SD above the mean of healthy controls) (2.6 vs 0.9; p=0.002, unpaired t test; figure 3B). 0000135265 00000 n The impact of vitamin D on dendritic cell function in patients with systemic lupus erythematosus. 0000012193 00000 n Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Kamen DL, Cooper GS, Bouali H, et al. Adults. Sandler, E.M. Simonsick, C.G. The estimated weighted prevalence of ANA positivity (score 3 or 4) was 17.5% in the U.S. population aged 50 and older. sharing sensitive information, make sure youre on a federal Forward and reverse primers for the genes MX1, PKR and IFIT, which are known to be highly and specifically induced by IFN, were used in the reaction.32 Background gene expression was controlled by amplifying glyceraldehyde 3-phosphate dehydrogenase. Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. **p=0.002 (unpaired t test). The hypothesis that vitamin D deficiency contributes to increased B cell activation in patients with SLE and increased production of autoantibodies, in particular those directed against nucleic acids, provides a mechanism for the association of vitamin D deficiency with increased IFN activity (working hypothesis shown in figure 4). Meier, Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): H.C.S. 0000260494 00000 n 2016 American Association for Cancer Research. A recent study sought to examine the effects of oral vitamin D supplementation on disease activity in SLE; however, more than 70% of the patients in the study still had insufficient levels of vitamin D after 2 years of treatment.36 While this study did not report any improvements in SLE disease activity after oral administration of vitamin D, interpretation of the results is limited by the small percentage of patients with SLE who achieved adequate 25(OH)D levels. NOTE: Bold text indicates statistical significance at P = 0.05. aRaoScott 2 for categorical variables, Wald F statistic for continuous variables. Helen C.S. Vacca A, Cormier C, Piras M, et al. National Library of Medicine All statistical analyses were carried out with GraphPad Prism Version 5.01 (GraphPad Software, San Diego, California, USA; http://www.graphpad.com). 426 0 obj <> endobj H\j@ 9& i{&c_>Xg?YZr2 !4rwm3gvipt9UrY]T|1u=^]n>wu:Om=^oxkD:5wg9v8Vt/Hg(@ZB/Z@h9QY@+6fYP !2B Bivariate relationships between ANA status, vitamin D category, and covariates were assessed using design-based RaoScott 2 and Wald F statistics. Serum 25(OH)D was measured with a radioimmunoassay kit (DiaSorin; refs. Serum IFN activity was measured in serum samples from patients with SLE and compared between patients with 25(OH) D levels >20 ng/ml (n=10) and <20 ng/ml (n=22). 0000005559 00000 n Error bars indicate SEM. The weighted prevalence for each ANA immunofluorescence intensity score (range, 04) was as follows: 0 to 1, 19.3%; 2, 63.2%; 3, 16.8%; and 4, 0.7%. Vitamin D deficiency influences immune responses through several pathways, including regulation of dendritic cells, T cells, and B cells (6). The role of vitamin D in regulating immune responses. Prevalence varied by sex (20.7% of females and 13.9% of males were ANA positive) and by race/ethnicity (15.9% of non-Hispanic white, 26.7% of non-Hispanic black and 21.9% of other were ANA positive), but only the sex difference was statistically significant (P = 0.02; Table 1). This work was supported by the Intramural Research Program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES049028; to DP Sandler), and the National Institute on Aging (AG000015-57; to EM Simonsick). When ANA prevalence was compared between non-Hispanic blacks and non-Hispanic whites, a statistically significant difference was observed (P = 0.05). Although no definitive study has been published demonstrating a beneficial effect of vitamin D supplementation on SLE disease severity, current knowledge supports vitamin D replacement for calcium homeostasis, bone health and potential immune system benefits. 0000000016 00000 n Interferon-alpha in systemic lupus erythematosus. Linker-Israeli M, Elstner E, Klinenberg JR, et al. 0000005110 00000 n Meier, D.P. 502 0 obj <>stream Peripheral blood was collected from each participant. 0000013397 00000 n Functional assay of type I interferon in systemic lupus erythematosus plasma and association with anti-RNA binding protein autoantibodies. Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. H\00Q(T/ X/;_\BO#8lm=7|kb{K"uS[]D8z5ynaMxjPshNF{}ov5e{-lqP|3Y:L|C/l. Errors bars indicate SEM. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Several indicators of health status and comorbid conditions, including high blood pressure, high triglycerides, high cholesterol, and smoking status, were investigated as potential confounders, but they were not associated with the exposure or outcome. An official website of the United States government. Hua J, Kirou K, Lee C, et al. Hajas A, Sandor J, Csathy L, et al. Vitamin D deficiency may contribute to immune dysregulation, resulting in the production of autoantibodies, in particular antinuclear antibodies (ANA; refs. 0000138070 00000 n This cross-sectional study of vitamin D deficiency and ANA in a middle-aged and older sample of the U.S. population found vitamin D deficiency to be associated with elevated odds of ANA compared with normal levels. Lvgren T, Eloranta ML, Bve U, et al. Median fluorescent intensity values for the levels of pERK1/2 were used on CD79a-gated B cells to rank and normalise the data. The authors would also like to thank J Anderson, W Klein, G Vidal and J Levin for their technical assistance, as well as S Stewart for his assistance with the statistical analysis. The relationship between vitamin D status and the interrelated pathways involving B cell activation, autoantibody production and IFN activity in SLE and healthy individuals was also evaluated. The 1982 revised criteria for the classification of systemic lupus erythematosus. Serum samples and plasma were isolated and stored at 20C until further use. In contrast, the 18 controls who were ANA-negative had significantly higher 25(OH)D levels than the patients with SLE (p<0.01, figure 1A). 0000007546 00000 n Kirou KA, Lee C, George S, et al. **p<0.01, KruskalWallis test with Dunns multiple comparison. Crow MK, Kirou KA. Toloza SM, Cole DE, Gladman DD, et al. (A) Patients with systemic lupus erythematosus (SLE) with 25-hydroxyvitamin D (25(OH)D) <20 ng/ml had mean (SD) serum IFN activity of 3.53 (6.56) compared with 0.34 (0.33) in patients with 25(OH)D >20 ng/ml. Orbach H, Zandman-Goddard G, Amital H, et al. 0000002551 00000 n Hochberg MC. 22). Frozen serum samples (20C) collected at mobile examination centers were shipped to the National Center for Environmental Health (Atlanta, GA) for testing. We used multivariate logistic regression to estimate prevalence ORs (POR) and 95% confidence intervals (CI), modeling the association between vitamin D deficiency and ANA adjusted for age, sex, race/ethnicity, education, season, and NHANES cycle, and in a second model, additionally adjusting for BMI and physical activity. Continuous serum 25(OH)D values were categorized as severe deficiency (<10 ng/mL), deficiency (1019.9 ng/mL), insufficiency (2029.9 ng/mL), and normal (30 ng/mL; ref. 0000185445 00000 n Copyright 2022 by the American Association for Cancer Research. ANA-positive participants were less likely or unable to engage in moderate or vigorous physical activity (P = 0.01). The fact that both ANA-positive healthy individuals and patients with SLE have decreased vitamin D suggests that the mechanism operates early in the steps to SLE development, before the appearance of clinical findings. 0000159970 00000 n The number of lupus-associated autoantibody specificities and 25(OH)D values are the predictor variables. Vitamin D insufficiency in a large female SLE cohort. A study was undertaken to explore the impact of low vitamin D levels on autoantibody production in healthy individuals, as well as B cell hyperactivity and interferon (IFN) activity in patients with systemic lupus erythematosus (SLE). Lower 25-hydroxyvitamin D (25(OH)D) levels are associated with increased B cell activation in patients with systemic lupus erythematosus (SLE). Pelajo CF, Lopez-Benitez JM, Miller LC. HHS Vulnerability Disclosure, Help Vitamin D deficiency could also contribute to an increased IFN signature in myeloid dendritic cells. 0000135528 00000 n Additional data (Supplementary material) are published online only. Analyses were performed using SAS version 9.3 (SAS Institute, Inc.), with PROC SURVEY procedures and Taylor series variance estimation to weight and adjust for strata and clustering of the complex survey design. 0000185914 00000 n This suggests that, although the number of autoantibody specificities and 25(OH)D levels are correlated (r2=0.138, p=0.037), both are good independent predictors of IFN activity. 0000022090 00000 n Weights to account for subsampling in the present sample were applied as described previously (14). Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). NHANES is a cross-sectional study, which limits the ability to determine causality of the association as temporality of exposure and outcome is not established. The sample was limited to adults aged 50 years old and older (n = 1,130) to focus on an age range where age-associated elevations in ANA become apparent and to avoid complex interactions between vitamin D and hormones in premenopausal women (14, 18). mRNA was purified from cell lysates and cDNA was made from total cellular mRNA. hb``d```f @adt`GwYIoj`X\uPGaCW>?~=?7=9*}Yg+R*TJb*Q%gm[~vwXNV!s8*| =nGkM__lsumNU7hS-G2|NPRRZvf..p/w`Py& Nucleic acids contained within autoantibody immune complexes can activate TLRs, thus promoting IFN production from plasmacytoid dendritic cells (pDCs) in patients with SLE.34 Vitamin D may bind vitamin D receptors present in pDCs and influence their IFN production, although it has been shown that 1,25(OH)2D did not modulate IFN production by pDCs in vitro at the concentrations used.35 Additionally, it has been shown that vitamin D suppresses the expression of the IFN signature in myeloid-derived dendritic cells (MDDCs). An increase in B cell activation as measured by pERK1/2 was correlated with decreased levels of 25(OH)D in patients with SLE (r=0.40, p=0.03; figure 2A). Before 0000202794 00000 n
Outdoor Sling Chair Fabric, Ocean Spa Hotel Cancun Restaurants, Tableau Server Cluster, Mexican Jewelry Store Near Me, Traveling Correctional Officer, Pressure Washer Repair Sarasota, Local Handmade Soaps Near Me, How Much Does It Cost To Make Toilet Paper,