Session Type: Abstract Session
Session Time: 3:00PM-3:50PM
Background/Purpose: Fractalkine (FKN) binds its receptor, CX3CR1 and accelerates chemotaxis of immune cells by inducing cell surface molecules and mediating adhesion of the cells to vascular endothelial cells. Several lines of evidence suggest that the FKN/CX3CR1 axis plays a crucial role in local infiltration of inflammatory cells at the sites of injury, which may result in impairments of organs in systemic lupus erythematosus (SLE). Our previous data showed that the expression level of CX3CR1 in peripheral CD14++CD16+ monocytes was remarkably decreased in SLE active patients as compared with SLE inactive patients and healthy controls (HC). In this study, we investigated the possible involvement of FKN/CX3CR1axis in immunological abnormalities and clinical features of SLE.
Methods: Fifty-nine SLE patients (SLEH; high disease activity, SLEDAI: >10, n = 32, SLEM+L; moderate and low disease activity, SLEDAI: < 10, n = 27) and 34 healthy controls (HC) were enrolled in this study. The expression level of CX3CR1 in peripheral CD14++CD16+ monocytes was analyzed by FACS using whole blood samples from patients and HC. The serum level of FKN was measured by a Slow Off-rate Modified DNA Aptamer (SOMAmer)-based capture array. Disease activities of SLE patients were quantified based on the SLEDAI scores. The serological data of the patients was collected by clinical records. Differences between the groups were examined for statistical significance by a t-test for single comparisons. Pearson’s correlation analysis was employed to evaluate the relationship between two continuous variables.
Results: FACS analysis revealed that the proportion of CX3CR1 positive cells among CD14++CD16+ monocytes was significantly lower in SLEH patients than in patients with SLEM+L (p = 0.007) or HC (p = 0.007), whereas the difference was not significant between SLEM+L and HC. Moreover, the CX3CR1+/CD14++CD16+ ratio was negatively and positively correlated with the SLEDAI score (p = 0.031) and serum level of C3 (p = 0.045), respectively, of all SLE patients. In addition, serum level of FKN was significantly higher in SLEH patients than those of SLEM+L patients (p = 0.005) and HC (p = 0.001). Interestingly, the serum FKN level was positively and negatively correlated with SLEDAI score (p = 0.0004) and C3 (p = 0.0043), respectively, of all SLE patients. Notably, the CX3CR1+/CD14++CD16+ ratio was negatively and significantly correlated with serum FKN level of the patients (p = 0.0078).
Conclusion: These results raised the possibility that reduced expression of CX3CR1 in peripheral CD14++CD16+ monocytes and the enhanced serum FKN level lead to acceleration of migration of FKN-stimulated CD14++CD16+ monocytes to organs.
To cite this abstract in AMA style:Yoshimoto K, Suzuki K, Seki N, Saito S, Kikuchi J, Takeuchi T. Possible Involvement of Fractalkine/CX3CR1 Axis in Peripheral CD14++CD16+ Monocytes in Disease Development of Patients with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/possible-involvement-of-fractalkine-cx3cr1-axis-in-peripheral-cd14cd16-monocytes-in-disease-development-of-patients-with-systemic-lupus-erythematosus/. Accessed January 17, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/possible-involvement-of-fractalkine-cx3cr1-axis-in-peripheral-cd14cd16-monocytes-in-disease-development-of-patients-with-systemic-lupus-erythematosus/