Possible Involvement of Toll-Like Receptors in the Pathogenesis of Myasthenia Gravis

Abstract

Toll-like receptors (TLRs), the innate immunity components, have been demonstrated to participate in multiple autoimmune diseases. However, our knowledge of the roles of TLRs in myasthenia gravis (MG) is still scarce. In this study, we detected the mRNA expression of TLR1 to TLR10 in peripheral blood mononuclear cells (PBMCs) of MG patients and the healthy controls by quantitative real-time polymerase transcription chain reaction. Our data demonstrate that aberrant expressions of TLRs exist in the PBMCs of MG patients and of the total, expression level of TLR9 mRNA has significantly positive relation with the clinical severity of MG, which suggests that TLRs may be involved in the pathogenesis of MG.

Gene/environment interactions in the pathogenesis of autoimmunity: New insights on the role of Toll-like receptors

“…mRNA expression of several TLRs was found to be highly altered in PBMCs obtained from MG patients in respect to non-MG patients: TLR2, TLR3, TLR4, TLR5, TLR8 and TLR9 expression was enhanced, whereas TLR1, TLR6 and TLR10 was diminished. Furthermore a correlation between TLR9 mRNA expression and MG clinical severity was observed; this envisages the potential involvement of TLR signaling pathway in MG pathogenesis [85]. Bernasconi et al [86] found that TLR4 was over-expressed in hyperplastic thymus from MG patients.…”

“…Increasing evidence has demonstrated the correlation between the presence of altered [82,83], vitiligo [84] and myasthenia gravis (MG) [85,86] (Table 1).…”

“…MG [85] nr T1D (rs5743612,-626 and rs4833095,-1017 in Chinese Han [64]). Early age at T1D diagnosis and poor glycemic control (rs5743313 and rs117221827) [105];…”

“…MG [85,86] nr RA (rs1927911 in Caucasians [70]); vitiligo (rs4986790, Asp299Gly in Turkish population [84]); IBD (rs4986790, Asp299Gly in Caucasians [79][80][81][189][190][191][192]; rs4986791, Thr399Ile in Caucasians [79][80][81][189][190][191][192]); SLE (D299G in South Indians [152]); CD (rs4986790, Asp299Gly [190]). …”

Cancer and the microbiome: potential applications as new tumor biomarker

“…TLRs can attach many PAMPs/DAMPs and it is thought that they may even attach regular 'self-' molecules including fibrinogen and heat shock proteins, suggesting a relation between the stereotypic inflammatory response mediated through TLRs and autoimmune diseases [106,107]. The signaling of TLRs is transduced in the cytoplasm through the Toll/IL-1 receptor domain (TIR), which is the site for docking to the cytoplasmic adaptor proteins of TIR that are important in coordinating the pathways of signal transduction after TLR as well as IL-1 receptor activation.…”