Review Vitamin D insufficiency in a large MCTD population Agota Hajas a , Janos Sandor b , Laszlo Csathy c , Istvan Csipo a , Sandor Barath a , Gyorgy Paragh d , Ildiko Seres d , Gyula Szegedi a , Yehuda Shoenfeld e , Edit Bodolay a, ⁎ a 3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary b Department of Preventive Medicine, Faculty of Public Health, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary c Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary d 1st Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary e Sheba Medical Center, Tel-Hashomer, Israel abstract article info Article history: Received 15 November 2010 Accepted 24 November 2010 Available online 13 December 2010 Keywords: Mixed connective tissue disease Vitamin D Autoantibodies Inflammatory cytokines Cardiovascular diseases Objectives: The aim of the present study was to evaluate the vitamin D status in patients with mixed connective tissue disease (MCTD) and to determine which clinical symptoms, laboratory parameters and endothelial cell markers are associated with low vitamin D levels. Methods: 125 female MCTD patients and 48 age- and sex-matched healthy controls were enrolled in the study. The clinical symptoms, autoantibodies (anti-U1-RNP, anti-cardiolipin — anti-CL and anti-endothelial cell antibody — AECA), serum cytokines (IFN-γ, IL-6, IL-12, IL-23, IL-17 and IL-10), soluble endothelial cell markers (endothelin, thrombomodulin — TM, and von Willebrand factor antigen — vWFAg) and serum lipids (total cholesterol, triglyceride, LDL-C, HDL-C, apolipoprotein A1, and apolipoprotein B) were investigated for an association with vitamin D levels by univariate and multivariate statistical analyses. Results: The mean vitamin D levels were significantly lower in MCTD patients, as compared with the control group (26.16 ± 13.50 ng/ml vs. 34.92 ± 9.64 ng/ml; p b 0.001). In laboratory parameters, vitamin D levels were inversely associated with serum IL-6 (p b 0.001), IL-23 (p = 0.011), IL-10 (p = 0.033) cytokine levels, TM (p = 0.001) and endothelin (p = 0.033) levels. Low vitamin D levels were also significantly associated with carotid artery intima media thickness (p b 0.001), fibrinogen (p = 0.010), total cholesterol (p = 0.042) and ApoA1 (p = 0.004) levels. Among the clinical symptoms, the cardiovascular involvement showed an inverse correlation with vitamin D status in MCTD (p b 0.001). Conclusions: The prevalence of vitamin D insufficiency is high in patients with MCTD. We assume that vitamin D insufficiency along with inflammatory parameters and lipid abnormalities may provoke cardiovascular events. © 2010 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318 2. Patients and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318 2.1. Laboratory examinations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318 2.1.1. Determination of vitamin D levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318 2.1.2. Immunoserological assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319 2.1.3. ELISA detection of plasma IFN-γ, IL-12, IL-17, IL-6, IL-23, and IL-10 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319 2.1.4. Carotid duplex ultrasound investigations: measurement of carotid artery intima media thickness (IMT) . . . . . . . . . . . 319 2.2. Statistical methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319 3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319 4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 4.1. Vitamin D and autoantibodies in MCTD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 4.2. Vitamin D level and inflammatory cytokines in MCTD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322 Autoimmunity Reviews 10 (2011) 317–324 ⁎ Corresponding author. Moricz Zs. str. 22, 4032 Debrecen, Hungary. Tel./fax: +36 52 255 218. E-mail address: edit.bodolay@gmail.com (E. Bodolay). 1568-9972/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2010.11.006 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev