can low vitamin d cause positive ana

Functional assay of type I interferon in systemic lupus erythematosus plasma and association with anti-RNA binding protein autoantibodies. 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. **p=0.002 (unpaired t test).

Meier, D.P. 2016 American Association for Cancer Research.

Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). 2016 AACR. Linker-Israeli M, Elstner E, Klinenberg JR, 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). 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. ANA positivity has been associated with vitamin D deficiency in autoimmune disease patients (1517), but little is known about vitamin D and ANA in healthy populations. Decreased T-cell regulation and increased B-cell activity may result in higher production of autoantibodies, including ANA (6). 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). 12).

0000002741 00000 n Karlson EW, Sanchez-Guerrero J, Wright EA, et al. Higher dilutions may be useful to identify individuals with higher levels of ANA in clinical settings; however, research on ANA in this NHANES sample was designed to obtain an estimate of ANA prevalence in the general population, most of whom do not have a diagnosis of autoimmune disease. 0000135920 00000 n 0000146938 00000 n endstream endobj 427 0 obj <>>>/Metadata 424 0 R/Names 428 0 R/Outlines 412 0 R/Pages 423 0 R/Type/Catalog/ViewerPreferences<>>> endobj 428 0 obj <> endobj 429 0 obj <>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/Rotate 0/Tabs/W/Thumb 417 0 R/TrimBox[0.0 0.0 595.276 841.89]/Type/Page>> endobj 430 0 obj [431 0 R] endobj 431 0 obj <>/Border[0 0 0]/H/N/Rect[444.871 793.605 543.251 783.094]/Subtype/Link/Type/Annot>> endobj 432 0 obj <> endobj 433 0 obj <> endobj 434 0 obj <> endobj 435 0 obj <> endobj 436 0 obj <> endobj 437 0 obj [/ICCBased 461 0 R] endobj 438 0 obj <> endobj 439 0 obj <> endobj 440 0 obj [466 0 R] endobj 441 0 obj <>stream 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. 0000003389 00000 n 0000004678 00000 n This observation suggests that vitamin D deficiency could be playing a role in the B cell hyperactivity seen in patients with SLE, thus contributing to an increased production of autoantibodies. ): H.C.S. HHS Vulnerability Disclosure, Help 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. 0000202794 00000 n <]/Prev 1074286>> Methods: A cross-sectional analysis using the National Health and Nutrition Examination Survey (NHANES) 20012004 was conducted. trailer official website and that any information you provide is encrypted 0000185914 00000 n The median (IQR) prednisone dosage for vitamin D-deficient patients was 3 (05) mg/day compared with 0 (05) mg/day for those not deficient in vitamin D (p=0.507, MannWhitney test). 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). 0000135528 00000 n 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. 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. The costs of publication of this article were defrayed in part by the payment of page charges. This relationship did not appear to be driven by differences in vitamin D distributions by race/ethnicity, based on the consistent pattern of higher ANA prevalence for relatively lower vitamin D levels (categorized by a race/ethnic specific median split) across all race/ethnic categories (Fig. In this study, IFN activity values >1 are considered high. sharing sensitive information, make sure youre on a federal

2011 Sep; 70(9): 15691574. Antinuclear antibody (ANA)-positive healthy individuals and patients with systemic lupus erythematosus (SLE) are more likely to be deficient in vitamin D. (A) Median (IQR) 25-hydroxyvitamin D levels were 17.3 (11.921.2) ng/ml in patients with SLE (n=32), 17.4 (14.525.8) ng/ml in ANA-positive controls (n=14) and 29.4 (19.036.3) ng/ml in ANA-negative controls (n=18). 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. 0000137770 00000 n Kirou KA, Lee C, George S, et al. Comorbid conditions or medications could contribute to the association between ANA and vitamin D. Ability to perform moderate/vigorous physical activity is only a crude indication of possibly comorbidity. Individuals of non-Hispanic black race/ethnicity, those having a higher BMI, lower educational attainment, and those not performing or unable to perform moderate or vigorous physical activity had a higher prevalence of vitamin D deficiency than their respective comparison groups (Supplementary Table S1). 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. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. The role of vitamin D in regulating immune responses.

0000021987 00000 n 1,25-Dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells.

Further investigation into ageANA associations specifically among older healthy populations is needed.

europe henry hallam state middle Vitamin D deficiency was not associated with age, sex, or collection season. 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). will also be available for a limited time.

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. 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. Vitamin D involvement in rheumatoid arthritis and systemic lupus erythematosus.

Ptrend = 0.04. 0000015359 00000 n Demographic information included sex, age and self-reported race. 0000003555 00000 n

Additional adjustment for BMI and physical activity had little impact on observed associations (severe deficiency POR: 2.64; 95% CI, 1.086.45; deficiency POR: 1.83; 95% CI, 1.013.30 and insufficiency POR: 2.01; 95% CI, 1.093.7; Ptrend = 0.05). Frozen serum samples (20C) collected at mobile examination centers were shipped to the National Center for Environmental Health (Atlanta, GA) for testing. Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. *p=0.02 (unpaired t test with Welchs correction of log-transformed data). europe henry hallam state middle 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. 0000271393 00000 n 0000136449 00000 n hb``d```f @adt`GwYIoj`X\uPGaCW>?~=?7=9*}Yg+R*TJb*Q%gm[~vwXNV!s8*| =nGkM__lsumNU7hS-G2|NPRRZvf..p/w`Py& 0000227130 00000 n 0000015491 00000 n 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.

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. 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). endstream endobj 442 0 obj <> endobj 443 0 obj <>stream 0000005586 00000 n fairfaxtimes 0000013002 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-double stranded DNA (dsDNA) antibodies were detected using a Crithidia luciliae indirect immunofluorescent assay (INOVA Diagnostics) according to the manufacturers instructions. 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. This article is featured in Highlights of This Issue, p. 1535.

These prior analyses that showed ANA increasing with age included a broader age range covering the life course from 12 to 70+ years (14). The SLE patient group had a median 25(OH)D level of 17.3 (IQR 11.921.2) ng/ml (figure 1A).

Error bars indicate SEM. 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. Additional data (Supplementary material) are published online only. Potential mechanism for the role of vitamin D in B cell hyperactivity, autoantibody production and interferon (IFN) activity. Demographic characteristics of ANA-positive and ANA-negative U.S. adults ages 50 years and older, NHANES 20012004, N = 1,012. 0000012193 00000 n jones constantine martin europe arnold hugh conversion bo1 books Continuous variables were analysed using an unpaired t test. Hormonal, environmental, and infectious risk factors for developing systemic lupus erythematosus.

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). CCL-25, American Type Culture Collection, Manassas, Virginia, USA) were cultured with 50% patient serum for 6 h and then lysed.

In a separate sensitivity analysis excluding participants with hypertension, the POR for the association between vitamin D deficiency and ANA was strengthened (POR severe deficiency excluding hypertensives: 3.81; 95% CI, 1.3310.89 versus 3.04; 95% CI, 1.257.40 including hypertensives), although less precise due to reduced sample size (final analytic N = 619).

Before This finding is interesting because patients with autoimmune disease, especially those with SLE, possess many risk factors for vitamin D deficiency whereas healthy controls do not. LCL, lower 95% confidence limit; UCL, upper 95% confidence limit. 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). Ben-Zvi I, Aranow C, Mackay M, et al. Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. 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. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C.

Lower 25-hydroxyvitamin D (25(OH)D) levels are associated with increased B cell activation in patients with systemic lupus erythematosus (SLE). While specific mechanisms have been discovered for the influence of vitamin D on innate immunity, the potential role for vitamin D in the adaptive immune system is still not clear. (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. 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). Niewold TB, Hua J, Lehman TJ, et al. 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). 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. Bivariate relationships between ANA status, vitamin D category, and covariates were assessed using design-based RaoScott 2 and Wald F statistics. 0000260906 00000 n Errors bars indicate SEM. Zold E, Szodoray P, Gaal J, et al. 0000069054 00000 n 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,

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). We thank Drs. Serum samples and plasma were isolated and stored at 20C until further use. HEp-2 cell slides (INOVA Diagnostics) with 1:80 dilution of sera were classified by intensities of immunofluorescence staining on a 0 to 4 scale based on comparison with a standard reference gallery (14). ANA-positive participants were less likely or unable to engage in moderate or vigorous physical activity (P = 0.01). NOTE: Bold text indicates statistical significance at P = 0.05. aRaoScott 2 for categorical variables, Wald F statistic for continuous variables. Vitamin D deficiency also influences B-cell homeostasis directly, resulting in hyperactive B cells and increased immunoglobulin production (6, 7). 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. Learn more

Conclusions: Among U.S. residents ages 50 and older, vitamin D deficiency was associated with higher prevalence of ANA. No potential conflicts of interest were disclosed. Vitamin D-deficient patients had a higher mean number of ACR classification criteria (6.4 vs 5.3; p=0.026, unpaired t test). Mean 25(OH)D levels were compared using the KruskalWallis test with the Dunn multiple comparisons post-test. europe david dr pdf prof chemistry books werner Cutolo M, Otsa K, Paolino S, et al. Donna Baird and Quaker Harmon for reviewing an earlier version of this manuscript. Weighted PORs (95% CI) of ANA by serum vitamin D level in the U.S. population age 50+, NHANES 20012004 (N = 1,012) adjusted for gender, age, education, race/ethnicity, season, and NHANES cycle. The 1982 revised criteria for the classification of systemic lupus erythematosus. Vitamin D deficiency could also contribute to an increased IFN signature in myeloid dendritic cells.

All the study participants provided written informed consent prior to enrolment. 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. Vitamin D sufficiency may be important for preventing immune dysfunction in older populations. Ruiz-Irastorza G, Egurbide MV, Olivares N, et al. 0000260225 00000 n 0000159970 00000 n Penna G, Amuchastegui S, Giarratana N, et al. 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).

Wright TB, Shults J, Leonard MB, et al. Cooper GS, Dooley MA, Treadwell EL, et al. 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. 0000068484 00000 n Ethics approval This study was conducted with the approval of the Oklahoma Medical Research Foundation (OMRF) and the University of Oklahoma Health Sciences Center. Welchs correction was used in instances of unequal variance. H\j@ 9& i{&c_>Xg?YZr2 !4rwm3gvipt9UrY]T|1u=^]n>wu:Om=^oxkD:5wg9v8Vt/Hg(@ZB/Z@h9QY@+6fYP !2B

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. Only European American women who are Oklahoma residents were included in the study in order to minimise variations in 25(OH)D levels due to race, sex and latitude. No correlation was seen between B cell activity and 25(OH)D levels in controls (pERK1/2: r=0.05, p=0.79).

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. Bethesda, MD 20894, Web Policies The new PMC design is here! The estimated weighted prevalence of ANA positivity (score 3 or 4) was 17.5% in the U.S. population aged 50 and older. Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Vitamin D insufficiency in a large MCTD population. 0000007249 00000 n

The coefficient of variation for the assay was calculated from blind QC pools and ranged from 6.5% to 11.3% for the 2001 to 2002 cycle and 4.4% to 13.2% for the 2003 to 2004 cycle (19, 20). Hajas A, Sandor J, Csathy L, et al. Figure 2 shows the adjusted weighted POR and 95% CI of ANA by serum vitamin D level.

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. Ann Rheum Dis.

Orbach H, Zandman-Goddard G, Amital H, et al. The 0000002551 00000 n Finally, NHANES does not include the institutionalized elderly, who are particularly prone to vitamin D deficiency; therefore, our findings may underestimate the relationship between vitamin D deficiency and ANA prevalence at older ages (27). Several mechanisms exist by which vitamin D could potentially modulate adaptive immune responses, including modulation of antigen presentation as well as direct actions on T and B lymphocytes. 0000068201 00000 n 0000017609 00000 n Adults. Supplementary Table 1 S1:Weighted Mean or Proportion for Covariates by Levels of Serum Vitamin D in the U.S. population ages 50 years and older in NHANES 2001-2004, N=1012 Supplementary Table 2 S2:Weighted prevalence odds ratios (95% CI) of ANA by serum vitamin D level in the U.S. population aged 50+, NHANES 2001-2004 (N=1,012). Controls completed the Connective Tissue Disease Screening Questionnaire (CSQ).28. 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). When ANA prevalence was compared between non-Hispanic blacks and non-Hispanic whites, a statistically significant difference was observed (P = 0.05). Heinlen LD, McClain MT, Ritterhouse LL, et al. Parks. This study also has limitations. Parks, Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc. Serum 25(OH)D was measured with a radioimmunoassay kit (DiaSorin; refs. diet tips weight thinspiration tricks lose ana pro plan exercise fast loss challenges foods mia low think 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). Vitamin D deficiency may contribute to immune dysregulation, resulting in the production of autoantibodies, in particular antinuclear antibodies (ANA; refs. Parks, Writing, review, and/or revision of the manuscript: H.C.S. Sandler, E.M. Simonsick, C.G. **p=0.003, *p=0.011 (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). Impact: Our findings support the growing evidence that vitamin D is an important immune modulator. We examined the prevalence of vitamin D deficiency in antinuclear antibody (ANA)-positive healthy individuals in comparison with ANA-negative healthy individuals and patients with SLE.

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