title: Impaired endothelial function in patients with undifferentiated connective tissue disease: a follow-up study.
abstract: OBJECTIVE
  In this study the alteration of endothelial function, arterial stiffness and autoantibodies was investigated in patients with UCTD.
  
  
  METHODS
  Thirty-one patients with UCTD were included in this prospective study. All the patients remained in the UCTD stage during the average 3.8 years follow-up period. The onset of UCTD was denoted as UCTD1, while the end of the follow-up period was called UCTD2. Flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT), autoantibodies [such as anti-SSA, anti-SSB, anti-DNA, anti-RNP, anti-CCP, aCL, anti-oxidized low-density lipoprotein (oxLDL) and AECA], von Willebrand factor antigen, thrombomodulin (TM), endothelin 1 (ET-1) and lipid parameters were measured.
  
  
  RESULTS
  In the UCTD1 stage, high-sensitivity CRP (hsCRP) and endothelial cell activation and/or damage markers such as TM, ET-1 and AECA levels were significantly higher compared with controls (controls vs UCTD1: hsCRP, P < 0.0001; TM, P = 0.001; ET-1, P < 0.0001). In the UCTD2 stage, the carotid IMT increased (UCTD1 vs UCTD2, P = 0.01) and FMD further deteriorated (UCTD1 and UCTD2, P = 0.001). In UCTD2 there was a close correlation between the carotid IMT, and duration of the disease (r = 0.612, P < 0.001), the level of TM (r = 0.673, P < 0.001) and anti-oxLDL (r = 0.800, P < 0.001).
  
  
  CONCLUSIONS
  Our data suggest that the presence of inflammation and autoantibodies provoke endothelial cell activation and/or injury in UCTD patients. The persistent endothelial dysfunction may provoke the development of atherosclerosis. FMD was found to be the most sensitive marker for arterial stiffness, and the increase of IMT clearly indicated the existence of preclinical atherosclerosis in UCTD patients.
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Laczik
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
authors.forename: Pal
authors.initials: P
authors.lastname: Soltesz
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Szodoray
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szekanecz
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Kerekes
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Paragh
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavölgyi
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Abel
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
authors.forename: Gyula
authors.initials: G
authors.lastname: Szegedi
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA edit.bodolay@gmail.com.
authors.forename: Edit
authors.initials: E
authors.lastname: Bodolay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001916:Brachial Artery / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging* / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000175:diagnosis / Q000503:physiopathology*; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology*; D055815:Young Adult
keywords: accelerated atherosclerosis; endothelial cell markers; endothelial dysfunction; flow-mediated vasodilation; undifferentiated connective tissue disease