title: Role of fractalkine in the pathogenesis of primary Sjögren syndrome: increased serum levels of fractalkine, its expression in labial salivary glands, and the association with clinical manifestations.
abstract: OBJECTIVE
  To investigate the expression of fractalkine and identify the clinical effects of fractalkine and its receptor (CX3CR1) in patients with primary Sjögren syndrome (pSS).
  
  
  METHODS
  Serum fractalkine levels were determined by ELISA. Immunohistochemical staining was done to compare the expression of fractalkine and CX3CR1 between salivary glands (SG) of patients with SS and controls. The cells to be merged with fractalkine were evaluated by confocal microscopy. Type of CX3CR1-expressing cells among infiltrating lymphocytes in SG was analyzed by confocal microscopy. Further, associations among fractalkine, proinflammatory cytokines, and clinical profiles were investigated.
  
  
  RESULTS
  Serum fractalkine levels in patients with pSS were higher than those in the control group (p = 0.026). SG expression of fractalkine and its receptor was upregulated in patients with pSS compared to that in the controls by immunohistochemistry. Higher histological grade was associated with more fractalkine-positive cells per total epithelial cells. Epithelial cells were the main fractalkine-expressing cell type in the SG. Serum fractalkine levels were significantly correlated with proinflammatory cytokines levels (interleukin 17: r = 0.685, p = 0.029; tumor necrosis factor-α: r = 0.444, p = 0.003), antinuclear antibody (r = 0.349, p = 0.022), and immunoglobulin G levels (r = 0.325, p = 0.044). Serum fractalkine levels in patients with extraglandular manifestations of pSS were significantly higher than in those without extraglandular manifestations (p = 0.026).
  
  
  CONCLUSIONS
  Fractalkine and CX3CR1 may play a role in the pathogenesis of pSS, including extraglandular manifestations.
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, School of Medicine, and the Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.J.H. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; S-K. Kwok, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S.M. Jung, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J.H. Ju, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S-H. Park, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor; H-Y. Kim, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor, Division of Rheumatology, Department of Internal Medicine, School of Medicine; J-S. Lee, Master's degree, Appointment Researcher; S.Y. Baek, Bachelor's degree, Appointment Researcher; E-K. Kim, Bachelor's degree, Appointment Researcher, Rheumatism Research Center, The Catholic University of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, School of Medicine, and the Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.J.H. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; S-K. Kwok, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S.M. Jung, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J.H. Ju, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S-H. Park, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor; H-Y. Kim, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor, Division of Rheumatology, Department of Internal Medicine, School of Medicine; J-S. Lee, Master's degree, Appointment Researcher; S.Y. Baek, Bachelor's degree, Appointment Researcher; E-K. Kim, Bachelor's degree, Appointment Researcher, Rheumatism Research Center, The Catholic University of Korea. seungki73@catholic.ac.kr.
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kwok
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, School of Medicine, and the Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.J.H. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; S-K. Kwok, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S.M. Jung, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J.H. Ju, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S-H. Park, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor; H-Y. Kim, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor, Division of Rheumatology, Department of Internal Medicine, School of Medicine; J-S. Lee, Master's degree, Appointment Researcher; S.Y. Baek, Bachelor's degree, Appointment Researcher; E-K. Kim, Bachelor's degree, Appointment Researcher, Rheumatism Research Center, The Catholic University of Korea.
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Jung
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, School of Medicine, and the Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.J.H. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; S-K. Kwok, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S.M. Jung, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J.H. Ju, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S-H. Park, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor; H-Y. Kim, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor, Division of Rheumatology, Department of Internal Medicine, School of Medicine; J-S. Lee, Master's degree, Appointment Researcher; S.Y. Baek, Bachelor's degree, Appointment Researcher; E-K. Kim, Bachelor's degree, Appointment Researcher, Rheumatism Research Center, The Catholic University of Korea.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lee
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, School of Medicine, and the Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.J.H. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; S-K. Kwok, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S.M. Jung, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J.H. Ju, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S-H. Park, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor; H-Y. Kim, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor, Division of Rheumatology, Department of Internal Medicine, School of Medicine; J-S. Lee, Master's degree, Appointment Researcher; S.Y. Baek, Bachelor's degree, Appointment Researcher; E-K. Kim, Bachelor's degree, Appointment Researcher, Rheumatism Research Center, The Catholic University of Korea.
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: Lee
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, School of Medicine, and the Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.J.H. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; S-K. Kwok, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S.M. Jung, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J.H. Ju, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S-H. Park, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor; H-Y. Kim, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor, Division of Rheumatology, Department of Internal Medicine, School of Medicine; J-S. Lee, Master's degree, Appointment Researcher; S.Y. Baek, Bachelor's degree, Appointment Researcher; E-K. Kim, Bachelor's degree, Appointment Researcher, Rheumatism Research Center, The Catholic University of Korea.
authors.forename: Seung Ye
authors.initials: SY
authors.lastname: Baek
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, School of Medicine, and the Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.J.H. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; S-K. Kwok, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S.M. Jung, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J.H. Ju, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S-H. Park, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor; H-Y. Kim, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor, Division of Rheumatology, Department of Internal Medicine, School of Medicine; J-S. Lee, Master's degree, Appointment Researcher; S.Y. Baek, Bachelor's degree, Appointment Researcher; E-K. Kim, Bachelor's degree, Appointment Researcher, Rheumatism Research Center, The Catholic University of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, School of Medicine, and the Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.J.H. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; S-K. Kwok, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S.M. Jung, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J.H. Ju, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S-H. Park, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor; H-Y. Kim, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor, Division of Rheumatology, Department of Internal Medicine, School of Medicine; J-S. Lee, Master's degree, Appointment Researcher; S.Y. Baek, Bachelor's degree, Appointment Researcher; E-K. Kim, Bachelor's degree, Appointment Researcher, Rheumatism Research Center, The Catholic University of Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ju
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, School of Medicine, and the Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.J.H. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; S-K. Kwok, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S.M. Jung, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J.H. Ju, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S-H. Park, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor; H-Y. Kim, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor, Division of Rheumatology, Department of Internal Medicine, School of Medicine; J-S. Lee, Master's degree, Appointment Researcher; S.Y. Baek, Bachelor's degree, Appointment Researcher; E-K. Kim, Bachelor's degree, Appointment Researcher, Rheumatism Research Center, The Catholic University of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, School of Medicine, and the Rheumatism Research Center, The Catholic University of Korea, Seoul, South Korea.J.H. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; S-K. Kwok, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S.M. Jung, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J. Lee, MD, Bachelor's degree, Appointment Physician, Rheumatology Specialist, Fellow; J.H. Ju, MD, PhD, Appointment Physician, Rheumatology Specialist, Associate Professor; S-H. Park, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor; H-Y. Kim, MD, PhD, Appointment Physician, Rheumatology Specialist, Professor, Division of Rheumatology, Department of Internal Medicine, School of Medicine; J-S. Lee, Master's degree, Appointment Researcher; S.Y. Baek, Bachelor's degree, Appointment Researcher; E-K. Kim, Bachelor's degree, Appointment Researcher, Rheumatism Research Center, The Catholic University of Korea.
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D016207:Cytokines; D019707:Receptors, Chemokine
keywords: CX3CR1; FRACTALKINE; SJÖGREN SYNDROME