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. 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. Pearson correlation was done to assess the relationship between pERK1/2 and 25(OH)D values. trailer Serum samples from 32 European American female patients with SLE and 32 matched controls were tested for 25-hydroxyvitamin D (25(OH)D) levels, lupus-associated autoantibodies and serum IFN activity. Weights to account for subsampling in the present sample were applied as described previously (14). While in vitro studies have demonstrated a suppressive action of vitamin D on Ig production and the IFN signature,18,24,25 an association between vitamin D status in patients with SLE and these disease features has not been previously reported. The observed association between vitamin D deficiency and ANA was unlikely due to including individuals who receive less vitamin D due to physical impairments or illness, as the association persisted in analyses restricted to those able to perform moderate or vigorous physical activity and free of rheumatoid arthritis or thyroid problems. (B) Patients with SLE with 25(OH)D levels <20 ng/ml had higher B cell activation (as measured by pERK1/2) than patients with 25(OH)D levels >20 ng/ml; *p=0.045 (unpaired t test with Welchs correction of log-transformed data). Vacca A, Cormier C, Piras M, et al. 0000135528 00000 n Vitamin D insufficiency in a large female SLE cohort. Parks, Writing, review, and/or revision of the manuscript: H.C.S. **p=0.003, *p=0.011 (Fisher exact test). 0000013397 00000 n Anti-double stranded DNA (dsDNA) antibodies were detected using a Crithidia luciliae indirect immunofluorescent assay (INOVA Diagnostics) according to the manufacturers instructions. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. 0000068484 00000 n Patients with SLE were evaluated for disease activity by the SELENA-modified SLE disease activity index (SELENA-SLEDAI), physician global assessment (PGA) and systemic lupus activity measure (SLAM). The estimated weighted prevalence of ANA positivity (score 3 or 4) was 17.5% in the U.S. population aged 50 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. ANA was not associated with age, education, race/ethnicity, BMI, or NHANES cycle. 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. 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). 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). **p=0.002 (unpaired t test). ANA intensity scores were confirmed independently by two experienced technicians who had an interrater agreement of greater than 95% (14). Ben-Zvi I, Aranow C, Mackay M, et al. Among individuals in the U.S. population ages 50 and older, vitamin D deficiency was associated with higher prevalence of ANA. Conception and design: H.C.S. We thank Drs. 0000003555 00000 n 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). IFN activity values reported represent the number of SD above the mean of healthy donors (n=141). Categorical data were analysed using the Fisher exact test. 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). PBMCs (1106) isolated by Ficoll-Paque gradients of fresh acid-citrate dextrose-anticoagulated blood were incubated at 37C for 15 min and then washed and permeabilised for 10 min with BD Phosflow Perm/Wash Buffer I (BD Biosciences, San Jose, California, USA).
0000003389 00000 n
Network analysis of associations between serum interferon- activity, autoantibodies, and clinical features in systemic lupus erythematosus. The costs of publication of this article were defrayed in part by the payment of page charges. Hypovitaminosis D is associated with greater body mass index and disease activity in pediatric systemic lupus erythematosus. 0000011074 00000 n
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. 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). Bethesda, MD 20894, Web Policies Kamen D, Aranow C. Vitamin D in systemic lupus erythematosus. Ruiz-Irastorza G, Egurbide MV, Olivares N, et al. 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). Serum samples were tested for IgG autoantibodies to human cellular antigens using standard immunofluorescence methods described previously (14). 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). Covariates included age, sex, education (less than high school, high school, greater than high school), race/ethnicity (non-Hispanic white, non-Hispanic black, or other), season of blood collection (summer or winter), body mass index (BMI; kg/m2), self-report of at least 10 minutes of moderate or vigorous physical activity in the past 30 days (yes, no, unable), and NHANES cycle. Toubi E, Shoenfeld Y. 0000159970 00000 n
Error bars indicate SEM. Of those, 118 participants with missing covariate information were excluded, resulting in a final sample of 1,012. ANA was measured using sera at a 1:80 dilution in NHANES. 0000137770 00000 n 0000002741 00000 n Vitamin D sufficiency may be important for preventing immune dysfunction in older populations. (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. Vitamin D and autoimmune rheumatologic disorders. 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.
This study has several strengths. Log-transformation was done to normalise serum IFN activity measures. 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. ANA was measured in a 1:80 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4+). Figure 2 shows the adjusted weighted POR and 95% CI of ANA by serum vitamin D level. Isolated peripheral blood mononuclear cells were tested for intracellular phospho-ERK 1/2 as a measure of B cell activation status. Methods: A cross-sectional analysis using the National Health and Nutrition Examination Survey (NHANES) 20012004 was conducted.
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