title: Association of circulating fractalkine (CX3CL1) and CX3CR1(+)CD4(+) T cells with common carotid artery intima-media thickness in patients with chronic kidney disease.
abstract: OBJECTIVE
  Fractalkine (CX3CL1), a chemokine, and its receptor CX3CR1 (expressed on T lymphocytes), have been shown to be abnormal in atherosclerosis. We investigated whether CX3CL1 levels and CX3CR1 expression were altered in patients with chronic kidney disease (CKD) and their association with common carotid artery intima-media thickness (CCA-IMT).
  
  
  METHODS
  CX3CR1 expression on CD4(+) T cells was analyzed by flow cytometry in 62 healthy controls (HC) and 128 Stage III-V CKD subjects. Fractalkine and highly sensitive C-reactive protein (hsCRP) were analyzed by ELISA. CCA-IMT was measured by ultrasound.
  
  
  RESULTS
  Compared to HC, CKD patients exhibited a 2.5-fold increase in the CD4(+)CX3CR1(+) T cell population (14.8±0.6 vs 5.9±0.34%, p < 0.0001). The expression of CX3CR1 was largely restricted to those CD4(+) cells that lacked CD28 co-stimulatory molecule. Fractalkine (pg/mL) and hsCRP (µg/mL) levels were increased in CKD subjects (510.6±61.6 vs. 239.7±9.67, p =0.003, and 93.8± 5.3 vs. 48.4±6.8, p < 0.0001), as was the CCA-IMT (0.71±0.01 vs. 0.56±0.01 mm, p < 0.0001). There was a significant relationship between CD4(+)CX3CR1(+) T cells and fractalkine levels (r = 0.2, p =0.01). CCA-IMT correlated positively with CX3CR1(+) T cells (r =0.34, p < 0.0001), CD4(+) CX3CR1(+) T cells (r =0.39, p < 0.0001), CD4(+)CD28(null)CX3CR1(+) T cells (r =0.23, p =0.02), fractalkine (r =0.3, p =0.001), age (r =0.33, p < 0.0001) and diabetes (p =0.01). On multiple regression, only CD4(+)CX3CR1(+) T cells and the presence of diabetes continued to show an association with IMT (p < 0.0001 and 0.0029 respectively).
  
  
  CONCLUSIONS
  CKD subjects showed an increase in CD4(+)CX3CR1(+) T cell population, plasma fractalkine and IMT; the association of CD4(+)CX3CR1(+) T cells and plasma fractalkine with CCA-IMT indicates that the fractalkine-CX3CR1 pathway may be important in the development and/or progression of atherosclerosis in CKD.
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Yadav
authors.forename: Anupam
authors.initials: A
authors.lastname: Lal
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Jha
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D054428:Chemokine CX3CL1 / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000097:blood*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine