can low vitamin d cause positive ana

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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). Vacca A, Cormier C, Piras M, et al. Vitamin D deficiency influences immune responses through several pathways, including regulation of dendritic cells, T cells, and B cells (6). Parks, Writing, review, and/or revision of the manuscript: H.C.S. 0000022090 00000 n official website and that any information you provide is encrypted Crow MK, Kirou KA. 0000006250 00000 n 0000012573 00000 n After adjustment, those with severe vitamin D deficiency (<10 ng/mL) had 2.99 (95% CI, 1.257.15) times the odds of ANA compared with having normal vitamin D levels (30 ng/mL), while deficient and insufficient individuals had twice the odds of ANA. Hormonal, environmental, and infectious risk factors for developing systemic lupus erythematosus. Vitamin D deficiency is probably not sufficient to cause B cell hyperactivation and autoantibody production, but rather is a contributing factor along with other genetic and environmental risks. Pearson correlation was done to assess the relationship between pERK1/2 and 25(OH)D values. 0000015902 00000 n 2016 American Association for Cancer Research. europe henry hallam state middle Cutolo M, Otsa K. Review: vitamin D, immunity and lupus. FOIA 0000271393 00000 n Severe deficiency and deficiency of vitamin D were combined due to small numbers. (B) Patients with SLE with low IFN activity (IFN activity <1 SD above the mean of healthy controls) had fewer mean number of autoantibody specificities than patients with high IFN activity (IFN activity >1 SD above the mean of healthy controls): 0.9 vs 2.1. Increased serum interferon (IFN) activity is associated with vitamin D deficiency and increased number of autoantibody specificities. 0000015491 00000 n 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. 0000135528 00000 n Greater vitamin D deficiency was associated with a higher prevalence of ANA (Ptrend = 0.0002). 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. Before Vitamin D deficiency was associated with an increased presence of autoantibodies in healthy controls. 0000017609 00000 n

IFN activity values reported represent the number of SD above the mean of healthy donors (n=141). 6, 7).

Orbach H, Zandman-Goddard G, Amital H, et al. 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. 0000006525 00000 n Toloza SM, Cole DE, Gladman DD, et al. Isolated peripheral blood mononuclear cells were tested for intracellular phospho-ERK 1/2 as a measure of B cell activation status. 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. **p=0.003, *p=0.011 (Fisher exact test). ELISAs were used to evaluate serum for antibodies to Sm, nuclear ribonucleoprotein (nRNP), Ro, La, ribosomal P (ribo P) and cardiolipin, as previously described.30 Samples were run in duplicate and normalised to a known positive control. Karlson EW, Sanchez-Guerrero J, Wright EA, et al. Pelajo CF, Lopez-Benitez JM, Miller LC. Error bars indicate SEM. American Association for Cancer Research. Wright TB, Shults J, Leonard MB, et al. Hochberg MC. **p<0.01, KruskalWallis test with Dunns multiple comparison. The mean age of the 14 ANA-positive controls was significantly higher than the ANA-negative controls (54.1 vs 42.8 years; p=0.029, unpaired t test). All 32 female patients with SLE met at least four of the American College of Rheumatology (ACR) classification criteria.26,27 Additionally, healthy individuals were recruited to provide control samples and were matched to the patients based on age (5 years), race and sex. The https:// ensures that you are connecting to the 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. Results: Greater vitamin D deficiency was associated with higher ANA prevalence in the unadjusted (Ptrend = 0.0002) logistic regression model and after adjustment for sex, age, education, race/ethnicity, season, and NHANES cycle (Ptrend = 0.04). 2011 Sep; 70(9): 15691574. (A) Increased B cell activation (as measured by phospho-ERK (pERK1/2)) was correlated with decreased 25(OH)D levels in patients with SLE (r=0.40, p=0.03). 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). (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. The Parks, Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc. 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). Of those, 118 participants with missing covariate information were excluded, resulting in a final sample of 1,012. 0000069054 00000 n 2016 AACR. Donna Baird and Quaker Harmon for reviewing an earlier version of this manuscript. Cutolo M, Otsa K, Paolino S, et al.

Vitamin D-deficient and insufficient individuals also had elevated odds of ANA (POR: 2.03; 95% CI, 1.163.55 and POR: 2.11; 95% CI, 1.153.88, respectively; Ptrend = 0.04). By continuing to use our website, you are agreeing to, Cancer Epidemiology, Biomarkers & Prevention, Collection: Early-Onset Colorectal Cancer, Collection: US Cancer Disparities Statistics, Collection: Cancer Epidemiology in Hispanic/Latino Populations, Collection: Colorectal Cancer: Screening and Early-Onset CRC, Collection: Informing Public Health Policy, Disclosure of Potential Conflicts of Interest, https://doi.org/10.1158/1055-9965.EPI-16-0339, http://www.cdc.gov/nchs/data/nhanes/nhanes_01_02/VID_B_met_Vitamin_D.pdf, http://www.cdc.gov/nchs/data/nhanes/nhanes_03_04/VID_C_met_Vitamin_D.pdf, http://wwwn.cdc.gov/Nchs/Nhanes/2001-2002/L06VID_B.htm, Cancer Epidemiology, Biomarkers, & Prevention. 0000135265 00000 n 1). One recent study examined this relationship in a small sample of clinical controls (7), but no population-based studies have been conducted. Data were available for 1,012 adults aged 50 years and older. 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. 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). Vitamin D deficiency in undifferentiated connective tissue disease. 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). This study also has limitations. Careers. 0000004104 00000 n Lvgren T, Eloranta ML, Bve U, et al. 0 The reporter cells (Wistar Institute, Susan Hayflick cells, ATCC No. 0000021987 00000 n Vitamin D deficiency in systemic lupus erythematosus. Vitamin D deficiency may contribute to immune dysregulation, resulting in the production of autoantibodies, in particular antinuclear antibodies (ANA; refs. Hua J, Kirou K, Lee C, et al. As the first analysis conducted in a large, U.S. representative sample, this adds to a suggestive literature on vitamin D deficiency and ANA based on clinical studies of lupus patients and one small sample of clinical controls (7, 15). ANAs were detected using an Hep-2 indirect immunofluorescent assay (INOVA Diagnostics, San Diego, California, USA) according to the manufacturers instructions. Errors bars indicate SEM. 0000007249 00000 n Accessibility 1,25-Dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells. 0000007546 00000 n ANA was not associated with age, education, race/ethnicity, BMI, or NHANES cycle. 0000014273 00000 n Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). 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. Detection of ANA at a dilution of 1:120 or greater and anti-dsDNA at a dilution of 1:30 or greater was considered a positive result.

Vitamin D deficiency remained associated with ANA (POR: 1.90; 95% CI, 1.053.42), while the association between vitamin D insufficiency and ANA did not reach statistical significance in this smaller subsample (POR: 1.56; 95% CI, 0.783.11). %PDF-1.7 % 0000146938 00000 n Helen C.S. Numerous studies have confirmed the association between raised IFN levels and increased disease activity in SLE.21 Strong evidence for the pathogenic role of IFN in SLE comes from clinical studies showing treatment with recombinant IFN for malignancies or hepatitis causes de novo SLE, with resolution after discontinuation of treatment.21 Induction of IFN from stimulation of TLRs by nucleic acid-containing immune complexes is thought to be one of the mechanisms by which patients with SLE have increased IFN activity.21 Supporting this hypothesis is evidence that activation of the IFN pathway is associated with the presence of autoantibodies directed against DNA and RNA binding proteins.22,23. Vitamin D deficiency also influences B-cell homeostasis directly, resulting in hyperactive B cells and increased immunoglobulin production (6, 7). Provenance and peer review Not commissioned; externally peer reviewed. 0000003555 00000 n Anti-Ro-positive patients in this small cohort were not more likely to have documented photosensitivity than anti-Ro-negative patients (60% vs 77%; p=0.450, Fisher exact test).

ANA-positive and ANA-negative controls had no significant difference in CSQ scores (median 1.0 (IQR 0.82.5) vs 1.0 (IQR 0.02.0); p=0.41, MannWhitney test). In addition, there was no difference in body mass index (BMI) values between ANA-positive and ANA-negative controls (26.1 vs 28.4 kg/m2; p=0.38, unpaired t test). and transmitted securely. 0000002741 00000 n Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Frozen serum samples (20C) collected at mobile examination centers were shipped to the National Center for Environmental Health (Atlanta, GA) for testing. Vitamin D deficiency is widespread and has been associated with many chronic diseases, including autoimmune disorders. 0000021917 00000 n 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. Niewold TB, Hua J, Lehman TJ, et al. Serum samples were tested for IgG autoantibodies to human cellular antigens using standard immunofluorescence methods described previously (14). We hypothesized that middle-aged and older individuals with vitamin D deficiency would have a higher prevalence of ANA than those with vitamin D levels in the normal range. 0000260906 00000 n 0000159724 00000 n

Vitamin D deficiency has been associated with several autoimmune diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), type 1 diabetes mellitus, inflammatory bowel disease (IBD), mixed connective tissue disease, autoimmune thyroid disease, scleroderma and systemic lupus erythematosus (SLE).19 Vitamin D levels are lower in individuals with undifferentiated connective tissue disease than in controls, and lower in patients who progressed to well-established connective tissue diseases than in those whose did not progress.10, Vitamin D supplementation has been shown to improve disease in murine models of MS, RA, type 1 diabetes mellitus, IBD and SLE.11 Addition of vitamin D and its synthetic analogues to murine models of SLE have resulted in improved dermatological disease, reduced proteinuria and increased survival.1 SLE is a complex heterogeneous autoimmune disorder arising from genetic predisposition and environmental risks.12,13 Vitamin D deficiency has been found in approximately two-thirds of patients with SLE, with approximately one-fifth of patients having severe deficiency (<10 ng/ml).2 Additionally, serum vitamin D levels have been shown to correlate inversely with disease activity.1416, Vitamin D has modulatory effects on B lymphocytes and Ig production.

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can low vitamin d cause positive ana