Background/Purpose: In our previous study, we have reported that IL-6 production was robustly increased in BAFF-stimulated peripheral monocytes of patients with primary Sjögren’s syndrome (pSS) and was positively and significantly correlated with the expression level of BAFF-receptor (BR3). We also found that the proportion of BR3-positive monocytes to total monocytes was positively and significantly correlated with the serum IgG level of pSS patients. In vitro analysis showed that IgG production by B cells was enhanced by co-cultured BAFF-stimulated monocytes probably through stimulation of B cells with IL-6 produced by the monocytes. These data collectively suggest that abnormal activation of monocytes is involved in the pathogenesis of pSS. It has been reported that the pathways via voltage-gated sodium channels in monocytic lineage are involved in production of inflammatory cytokines, such as IL-6 in inflammatory pain diseases. In this study, we investigated the localization and the expression level of ion channels, such as Nav1.7, a voltage-gated sodium channel, in peripheral monocytes in patients with pSS in an attempt to discriminate the disease from other autoimmune diseases, such as active RA and active SLE.

Methods: The expression level of Nav1.7 in peripheral monocytes was analyzed by FACS using whole blood samples from patients with pSS (n = 28), active RA (n = 15), active SLE (n = 37) and healthy controls (HC; n = 15). Monocytes were prepared from whole blood samples and stimulated with recombinant human soluble BAFF (sBAFF) in the presence or absence of an inhibitor against Nav1.7. The amount of IL-6 in the culture supernatants and the expression level of Nav1.7 in the cells were analyzed by ELISA and qPCR, respectively.

Results: FACS analysis revealed that the expression level of Nav1.7 in pSS monocytes was significantly higher than those of active RA (p = 0.005), active SLE (p <0.001) and HC (p < 0.001). In addition, the expression level of BR3 in pSS monocytes was significantly higher than those of HC (p = 0.048), RA (p = 0.037) and SLE (p = 0.024). Interestingly, the expression level of Nav 1.7 in pSS monocytes was significantly and positively correlated with that of BR3 in the cells (p = 0.02). Moreover, a specific inhibitor against Nav 1.7 suppressed IL-6 production by sBAFF-stimulated peripheral monocytes in a dose dependent manner. In addition, qPCR analysis indicated that Nav 1.7 expression in pSS monocytes was induced upon stimulation with sBAFF.

Conclusion: Our results strongly suggest that the crosstalk between BAFF signaling and sodium channel is involved in activation of pSS monocytes and can be a therapeutic target for pSS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/localization-of-the-voltage-gated-sodium-channel-1-7-in-peripheral-monocytes-contributes-to-activation-of-baff-signaling-in-monocytes-of-patients-with-primary-sjogrens-syndrome/