Activation of the receptor for advanced glycation end products (RAGE) exacerbates experimental autoimmune myasthenia gravis symptoms

RAGE belongs to immunoglobulin superfamily and serves as a ligand for various immunoregulatory molecules including S100B that has been demonstrated important to T cell mediated autoimmune diseases. In this context, we hypothesized that RAGE could also impact B cell mediated, T cell-dependent autoimmune diseases. This was tested using myasthenia gravis (MG) animal model, EAMG. We show that expression of both RAGE and S100B are increased during EAMG and the interaction between RAGE and S100B affected the Th1/Th2/Th17/Treg cell equilibrium, up-regulate AChR-specific T cell proliferation. Furthermore, addition of S100B in vitro stimulated splenocyte activity linked to COX-2 up-regulation. NS-398, a selective COX-2 inhibitor, effectively diminished S100B mediated activity of AChR-specific antibody secreting splenocytes. These findings suggested that a reciprocal relationship between RAGE and S100B promoted the development of EAMG, highlighting the importance of understanding the mechanisms of EAMG disease as a means of developing new therapies for the treatment of MG.

► The expression of both RAGE and S100B was highly up-regulated in EAMG. ► The interaction between RAGE and S100B could up-regulate AChR-specific T cell proliferation. ► The distribution of CD4+ T cells were effected after stimulated by S100B in the progression of EAMG. ► The interaction of RAGE and S100B increased the number of anti-AChR IgG antibody secreting splenocytes by the pathway of COX-2 in a concentration- and time-dependent manner ► Blocking RAGE pathway could ameliorate EAMG.