In single-predictor logistic regression models, both 25(OH)D (p=0.033) and number of autoantibody specificities (p=0.023) are significantly associated with IFN activity. The https:// ensures that you are connecting to the Adults. We performed sensitivity analyses after excluding those with self-reported rheumatoid arthritis or thyroid problems, those unable to perform moderate physical activity, and premenopausal females (final analytic N = 747). 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). Functional assay of type I interferon in systemic lupus erythematosus plasma and association with anti-RNA binding protein autoantibodies. Ethics approval This study was conducted with the approval of the Oklahoma Medical Research Foundation (OMRF) and the University of Oklahoma Health Sciences Center. A connective tissue disease screening questionnaire for population studies. Ben-Zvi I, Aranow C, Mackay M, et al. Patients with high B cell activation had lower mean (SD) 25(OH)D levels than patients with low B cell activation (17.2 (5.1) vs 24.2 (3.9) ng/ml; p=0.009). Of those, 118 participants with missing covariate information were excluded, resulting in a final sample of 1,012. While vitamin D deficiency has been reported in many autoimmune diseases, this is the first observation in ANA-positive healthy individuals. 0000249202 00000 n
Parks, Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc. Among individuals in the U.S. population ages 50 and older, vitamin D deficiency was associated with higher prevalence of ANA.
ANAs were detected using an Hep-2 indirect immunofluorescent assay (INOVA Diagnostics, San Diego, California, USA) according to the manufacturers instructions. 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). 
0000185914 00000 n
This increase in autoantibody production, specifically of antibodies directed against self-nucleic acids, could lead to an increase in IFN production by plasmacytoid dendritic cells via Toll-like receptor (TLR) signalling mediated by immune complexes. Vitamin D deficiency was associated with an increased presence of autoantibodies in healthy controls. Cutolo M, Otsa K, Paolino S, et al. Funding This work was supported by the National Institutes of Health (NIAID: HHSN266200500026C, AR058554, RR015577, AI082714, AI24717, AR24260, AI083194, AR052364 and AR053483), Kirkland Foundation Scholar Support, OMRF J Donald Capra Fellowship Support, US Department of Veteran Affairs and the OMRF Lou C Kerr Chair in Biomedical Research. cDNA was then quantified using real-time PCR. Conclusions: Among U.S. residents ages 50 and older, vitamin D deficiency was associated with higher prevalence of ANA. Beyond considering the molecular mechanisms by which vitamin D deficiency would predispose to autoimmunity, the extraordinarily high prevalence of vitamin D deficiency in ANA-positive healthy individuals and patients with SLE strongly suggests that repletion with vitamin D should be considered.
Vitamin D-deficient patients had a mean (SD) serum IFN activity of 3.5 (6.6) compared with 0.34 (0.33) in non-vitamin D-deficient patients. Decreased T-cell regulation and increased B-cell activity may result in higher production of autoantibodies, including ANA (6). 426 0 obj <> endobj
No correlation was seen between B cell activity and 25(OH)D levels in controls (pERK1/2: r=0.05, p=0.79). 0000015491 00000 n Increased serum interferon (IFN) activity is associated with vitamin D deficiency and increased number of autoantibody specificities. 0000005333 00000 n Cancer Epidemiol Biomarkers Prev; 25(12); 155963. Hochberg MC. Conception and design: H.C.S. 0000249947 00000 n
FOIA 0000185196 00000 n %%EOF
Many autoimmune diseases were not assessed in NHANES, but disease-specific autoantibodies were uncommon in prior reports (14), and the onset of most autoimmune disease in older age is rare (26). Ruiz-Irastorza G, Gordo S, Olivares N, et al. Interestingly, this same correlation was not seen in the controls, suggesting a potential geneenvironment interaction between SLE susceptibility genes and vitamin D. In this manner, vitamin D deficiency would contribute to B cell hyperactivation and autoantibody production in genetically susceptible individuals. official website and that any information you provide is encrypted 0000010054 00000 n Serum 25(OH)D was measured with a radioimmunoassay kit (DiaSorin; refs. Weights to account for subsampling in the present sample were applied as described previously (14). 0000012193 00000 n PORs and 95% CIs for unadjusted and adjusted models are listed in Supplementary Table S2. 0000002777 00000 n 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). 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. 0000015902 00000 n The number of lupus-associated autoantibody specificities and 25(OH)D values are the predictor variables. This article is featured in Highlights of This Issue, p. 1535. One recent study examined this relationship in a small sample of clinical controls (7), but no population-based studies have been conducted.
Understanding the role of vitamin D in immune modulation, particularly in aging populations susceptible to vitamin D deficiency, may also help identify preventative or clinical opportunities to improve immune function and delay immunosenescence. The objective of this study was to determine whether vitamin D deficiency is associated with ANA in middle-aged and older U.S. adults.
0000202387 00000 n Vitamin D insufficiency in a large female SLE cohort. 0000005110 00000 n
IFN activity values reported represent the number of SD above the mean of healthy donors (n=141). Demographic information included sex, age and self-reported race. A hallmark of autoimmune disease is the presence of self-reactive autoantibodies, which are also of interest as immunologic biomarkers of cancer (911). An official website of the United States government. 0000227130 00000 n
0000202794 00000 n
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. 0000159970 00000 n
0000015359 00000 n
American Association for Cancer Research. endstream
endobj
442 0 obj
<>
endobj
443 0 obj
<>stream
Bars indicate IQR. 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. Data from NHANES 2003 to 2004 cycle were adjusted for assay drift (21). Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. 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%. Further investigation into ageANA associations specifically among older healthy populations is needed. (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. B, Weighted prevalence (95% CI) of ANA by race/ethnic-specific vitamin D levels in the U.S. population ages 50+, NHANES 20012004 (N = 1,012); low,
6, 7). Karlson EW, Sanchez-Guerrero J, Wright EA, et al. 0000013397 00000 n
502 0 obj <>stream 0000111775 00000 n Interestingly, the 14 controls who were ANA-positive had a median 25(OH)D level of 17.4 (14.525.8) ng/ml, which was not statistically different from the patients with SLE (KruskalWallis test with Dunns post-test). Plasma 25(OH)D levels were determined in duplicate using an enzyme immunoassay kit (Immunodiagnostic Systems, Scottsdale, Arizona, USA) according to the manufacturers instructions. Kamen DL, Cooper GS, Bouali H, et al. Errors bars indicate SEM. Lvgren T, Eloranta ML, Bve U, et al. sharing sensitive information, make sure youre on a federal 1). Sandler, E.M. Simonsick, C.G. Ptrend = 0.04. 0000202132 00000 n Vitamin D deficiency (25(OH)D <20 ng/ml) was significantly more frequent among patients with SLE (n=32, 69%) and antinuclear antibody (ANA)-positive controls (n=14, 71%) compared with ANA-negative controls (n=18, 22%) (OR 7.7, 95% CI 2.0 to 29.4, p=0.003 and OR 8.8, 95% CI 1.8 to 43.6, p=0.011, respectively). 0000135947 00000 n vitamin deficiency pregnant
trailer Elevated ANA is sometimes found in healthy individuals and has been consistently associated with female sex and older age (1214). Potential mechanism for the role of vitamin D in B cell hyperactivity, autoantibody production and interferon (IFN) activity. 0000147351 00000 n 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).
0000019267 00000 n 22). Orbach H, Zandman-Goddard G, Amital H, et al. 0000227385 00000 n 25(OH)D levels were measured in 32 European American female patients with SLE and in 32 healthy matched controls. 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).
Serum samples and plasma were isolated and stored at 20C until further use. 0000006525 00000 n Experiments were performed in accordance with the Helsinki Declaration and approved by the Institutional Review Boards at the Oklahoma Medical Research Foundation and the University of Oklahoma Health Sciences Center. 0000013002 00000 n Meier, D.P. Although increasing evidence supports the role of vitamin D in modulating the immune system, many details remain to be elucidated. 0000136449 00000 n This study also has limitations. 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. 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. HHS Vulnerability Disclosure, Help Furthermore, when categorised into vitamin D-deficient (25(OH)D <20 ng/ml) or non-deficient (25(OH)D >20 ng/ml), patients with SLE and ANA-positive controls were more likely to be vitamin D deficient (69% and 71%, respectively) than ANA-negative controls (22% deficient) (OR 7.7, 95% CI 2.0 to 29.4, p=0.003 and OR 8.8, 95% CI 1.8 to 43.6, p=0.011, respectively, Fisher exact test, figure 1B). ANA was measured using sera at a 1:80 dilution in NHANES. Amital H, Szekanecz Z, Szcs G, et al. 0000227852 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. Vitamin D is inversely associated with cancer incidence, progression, and mortality in many observational studies, although results from randomized clinical trials are less clear (14). The reporter cells (Wistar Institute, Susan Hayflick cells, ATCC No. 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). 0000271393 00000 n Crow MK, Kirou KA. 0000068484 00000 n Interferon-alpha in systemic lupus erythematosus. 0000135528 00000 n Demographic characteristics of ANA-positive and ANA-negative U.S. adults ages 50 years and older, NHANES 20012004, N = 1,012. 0000111871 00000 n Serum samples were tested for IgG autoantibodies to human cellular antigens using standard immunofluorescence methods described previously (14). Chen S, Sims GP, Chen XX, et al. Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. In this sample restricted to middle-aged and older U.S. adults, ANA was not observed to increase with age in contrast to previous reports using NHANES data (14, 25). Provenance and peer review Not commissioned; externally peer reviewed. 0000260225 00000 n
- Peach Slices Snail Rescue Toner Ingredients
- Avery 5260 Template Excel
- Professional Skincare
- Steve Madden Uplift Gold
- Small Gas Powered Water Pump
- Aesop Istros Aromatique Room Spray
- Raised Spot Uv Business Cards
- 3 Phase 4 Wire Energy Meter Reading
- Independent Front Suspension Kits
- Marathon Analog Alarm Clock Manual
- Dinner Party Trivia Games
- Morning Chess Perfume 50ml