br Conclusions and future directions Translation

Conclusions and future directions Translation of the therapy to human MG will require a substitute adjuvant for IFA. Most human vaccines use aluminum salts (alum) as adjuvants. Both IFA and alum selectively promote antibody dominated Th 2 immune responses, rather than T killer cell dominated Th 1 responses [119]. It is likely that alum will be as effective as IFA because of the beneficial effects of the Th2 response in the therapy. This basic approach to specific immunosuppressive therapy by immunization with cytoplasmic domains should be effective on antibody-mediated autoimmune responses to any transmembrane protein. In principle, autoimmune responses to Musk and LRP4, both of which are transmembrane proteins with cytoplasmic domain, should be able to be antigen-specifically suppressed by similar approaches. Another candidate for this approach is autoimmune response to glutamate receptors [120].
Conflict of interest
Acknowledgements
Introduction Myasthenia gravis (MG) is an antibody-mediated autoimmune inflammatory disease characterized by impaired neuromuscular transmission. Approximately 85% of patients with MG produce antibodies to the nicotinic line receptor (AChR, AChR-MG). These autoantibodies are implicated in neuromuscular transmission failure in MG (Vincent and Newsom-Davis, 1985), and their production depends on the activation of T-helper cells and B cells (Tackenberg et al., 2007). Interactions among T cells, B cells, and cytokines play significant roles in the pathogenic inflammation of the neuromuscular junction in the disorder, which impairs neuromuscular transmission (Uzawa et al., 2014a). Resistin is a peptide hormone secreted by adipocytes in mice (Steppan et al., 2001), but it is mainly expressed in macrophages and monocytes in humans (Patel et al., 2003). It has been reported that resistin has important roles in the human immune response and inflammation (Fadda et al., 2013, Malyszko et al., 2006). Resistin acts as a pro-inflammatory mediator that induces the expression of various cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (Nagaev et al., 2006). Recent studies have demonstrated relationships between resistin and inflammatory activity in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and idiopathic inflammatory myopathies (Almehed et al., 2008, Filkova et al., 2013, Migita et al., 2006). However, serum resistin levels in patients with MG have not been described. In the present study, we therefore measured serum resistin level in selected AChR-MG patients and investigated their possible relationship with various clinical and treatment parameters.
Methods
Results The presenting demographic and clinical features of the 102 patients with AChR-MG are shown in Table 1. All the participants belonged to the Chinese Han ethnic group. We observed significantly higher serum resistin levels in AChR-MG patients compared to controls (p<0.001, Fig. 1A). When we compared resistin levels among different MG subtypes, patients with GMG had significantly higher resistin levels than patients with OMG (p<0.001) and control subjects (p<0.001, Fig. 1A). In contrast, there was no significant difference between patients with OMG and control subjects (p=0.414, Fig. 1A). We found that patients with MG with thymoma had significantly higher resistin levels than both MG patients without thymoma (p=0.001, Fig. 1B) and control subjects (p<0.001, Fig. 1B). The patients with MG without thymoma also had higher resistin levels than control subjects (p<0.001, Fig. 1B). When we examined the mean resistin level in patients with MG with thymoma, we found that it was significantly higher than in both patients with GMG without thymoma and controls (p=0.009 and p<0.001, respectively; Fig. 1B). There were no differences in resistin levels in patients with OMG without thymoma (p=0.091, Fig. 1B), but levels were higher in OMG patients with thymoma compared to controls (p=0.019, Fig. 1B).