The serum BAFF levels in patients with MG were significantly elevated, although the levels were not correlated with the clinical severity (140). In patients with NMO, the numbers of CD19intCD27highCD38highCD180B cell PBs are selectively elevated in the peripheral blood and further expanded during relapse; these cells are responsible for the generation of AQP4 antibodies in an IL-6-dependent manner (142). the thymus but not the targetmuscle in MG, whereas the infiltration of inflammatory cells, mainly polymorphonuclear leukocytes and macrophages, in NMO, is always observed in the target organthe spinal cord. A review of the common and discrepant characteristics of these two autoimmune channelopathies may expand our understanding of the pathogenic mechanism of both disorders and assist in the development of proper treatments in the future. Keywords:neuromyelitis optica spectrum disorders, myasthenia gravis, channelopathy, humoral immunity, inflammation == Introduction == Myasthenia gravis (MG) is an autoimmune disease in which antibodies target postsynaptic membrane components at the neuromuscular junction (NMJ) and is characterized by fluctuating muscle weakness and fatigue (13). MG involves specific skeletal muscles, frequently including ocular, bulbar, and proximal extremity muscles but also affects respiratory muscles in severe cases (4,5). The disease begins with an acute or subacute onset, improves with spontaneous remission or treatment, and relapses after variable intervals (6,7). As the most important biomarkers FK-506 (Tacrolimus) in diagnosis, antibodies comprise a series of immunoglobulins (Igs) binding to acetylcholine receptors (AChR)an ion channel protein, muscle-specific kinase (MuSK), and lipoprotein receptor-related protein 4 (LRP4) or other postsynaptic proteins (4). Based on the antibody profile, clinical presentation, age of onset, and thymic pathology, patients can be divided into several subtypes: MG with anti-AChR antibodies (AChR-MG) of early-onset, late-onset or with thymoma; MG with anti-MuSK antibodies (MuSK-MG); MG with anti-LRP4 antibodies (LRP4-MG); ocular MG; and seronegative MG (1,4). MG has a prevalence of 1525 cases per 100,000 individuals and an annual incidence of 0.81 cases per 100,000 individuals (1,8), and AChR-MG constitutes approximately 80% of all MG cases (4,5). The age of onset and the female-to-male ratio varies between different subtypes (2,4,5). The disease is usually well controlled by immunosuppressive, symptomatic, supportive, or surgical treatment in most patients; however, only a few patients (22.2% of AChR-MG, 3.6% of MuSK-MG, and 21.9% of others) obtain full remission (1,4,9). Neuromyelitis optica (NMO) is a severe, idiopathic, demyelinating disorder of the central nervous system (CNS) that has recently been recognized to be distinct from the classic demyelinating diseasemultiple sclerosis (MS). NMO preferentially affects the optic nerve and spinal cord, but relatively spares the brain (10). With the discovery of the diagnostic biomarkerNMO-IgG (11), a better understanding of the pathogenesis of the disease was obtained and the clinical entity evolved. In 2015, the diagnostic criteria adopted the term neuromyelitis optica spectrum disorders FK-506 (Tacrolimus) (NMOSD) to incorporate inaugural or limited forms of NMO (idiopathic single or recurrent longitudinally extensive myelitis or recurrent or simultaneous bilateral optic neuritis), the involvement of the brain, coexistence with other autoimmune disorders, and Asian opticospinal MS (12). Most patients are seropositive for Ig G against aquaporin-4 (AQP4-IgG) (1316), which is the most abundant water channel protein in astrocytes throughout the CNS (17,18). Approximately 510% of patients are seropositive for antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) (1921), and a few patients are dual-positive for both antibodies (22,23). The prevalence and incidence of NMO/NMOSD are approximately 3.910 and 0.070.73 per 100,000, respectively, the median age of onset is 3537 years and the Rabbit polyclonal to ZNF280A female-to-male ratio is approximately 89:1 (24). Most patients have a relapsing course, with the interval between attacks ranging from months to years; the subsequent accumulation of disability leads to a poor prognosis despite the use of immunosuppressive treatment (10,16,25). As autoimmune channelopathies in the periphery and CNS, MG and NMO share many similarities: (i) they develop based on a synergy between genetic factors and environmental effects (26,27), (ii) the common female dominance in the prevalence of some major subtypes suggests an influence of gender on both diseases (28,29), (iii) both depend on T cell-mediated, B cell-dependent immunopathology and the effects of antibodies and complements (30,31), (iv) patients with the FK-506 (Tacrolimus) two disorders display similar relapsing courses and require chronic immunomodulatory management (1,7,10), (v) the disorders frequently coexist with other systemic or organ-specific autoimmune disorders (32,33), and (vi) AChR-IgG and AQP4-IgG have been co-detected in patients with MG and NMOSD in.