AIM: 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.
AIM: 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: Rachana Shah; Gregory J Matthews; Rhia Y Shah; Catherine McLaughlin; Jing Chen; Melanie Wolman; Stephen R Master; Boyang Chai; Dawei Xie; Daniel J Rader; Dominic S Raj; Nehal N Mehta; Matthew Budoff; Michael J Fischer; Alan S Go; Raymond R Townsend; Jiang He; John W Kusek; Harold I Feldman; Andrea S Foulkes; Muredach P Reilly Journal: Am J Kidney Dis Date: 2015-03-17 Impact factor: 8.860
Authors: Lei Dong; Johannes Nordlohne; Shuwang Ge; Barbara Hertel; Anette Melk; Song Rong; Hermann Haller; Sibylle von Vietinghoff Journal: J Am Soc Nephrol Date: 2015-10-08 Impact factor: 10.121
Authors: Marcin Moniuszko; Barbara Glowinska-Olszewska; Malgorzata Rusak; Marta Jeznach; Kamil Grubczak; Danuta Lipinska; Robert Milewski; Anna Justyna Milewska; Milena Dabrowska; Ewa Jablonska; Adam Kretowski; Maria Gorska; Anna Bodzenta-Lukaszyk; Artur Bossowski Journal: Clin Dev Immunol Date: 2013-11-21
Authors: Ligia Maria Claro; Andrea N Moreno-Amaral; Ana Carolina Gadotti; Carla J Dolenga; Lia S Nakao; Marina L V Azevedo; Lucia de Noronha; Marcia Olandoski; Thyago P de Moraes; Andréa E M Stinghen; Roberto Pécoits-Filho Journal: Toxins (Basel) Date: 2018-09-23 Impact factor: 4.546