Immunopathogenesis in Myasthenia Gravis and Neuromyelitis Optica

Abstract

Myasthenia gravis (MG) and neuromyelitis optica (NMO) are autoimmune channelopathies of the peripheral neuromuscular junction (NMJ) and central nervous system (CNS) that are mainly mediated by humoral immunity against the acetylcholine receptor (AChR) and aquaporin-4 (AQP4), respectively. The diseases share some common features, including genetic predispositions, environmental factors, the breakdown of tolerance, the collaboration of T cells and B cells, imbalances in T helper 1 (Th1)/Th2/Th17/regulatory T cells, aberrant cytokine and antibody secretion, and complement system activation. However, some aspects of the immune mechanisms are unique. Both targets (AChR and AQP4) are expressed in the periphery and CNS, but MG mainly affects the NMJ in the periphery outside of CNS, whereas NMO preferentially involves the CNS. Inflammatory cells, including B cells and macrophages, often infiltrate the thymus but not the target—muscle in MG, whereas the infiltration of inflammatory cells, mainly polymorphonuclear leukocytes and macrophages, in NMO, is always observed in the target organ—the 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.

Autoimmune diseases associated with Neuromyelitis Optica Spectrum Disorders: A literature review

“…Some common genetic and environmental risk factors such as HLA subtypes and non-HLA genes predisposing autoimmunity, Vitamin D deficiency, and evidence of EBV infection may lead to co-existence of both diseases. Furthermore, AQP4 presence in neuromuscular junction and destruction of postsynaptic membrane by AChR antibodies cause the AQP4 channels to be exposed to immune system for producing antibodies [82].…”

Myasthenia gravis and specific immunotherapy: monoclonal antibodies

“…The AChR–immune complex interacts with antigen‐presenting cells, CD4 + T cells, and B cells to produce a large number of AChR Abs, which can directly attack AChRs on the postsynaptic membrane of the NMJ through circulating blood, accelerating their degradation and leading to a decrease in their number in the postsynaptic membrane, ultimately affecting NMJ function and promoting MG (Fig. ) …”

Myasthenia gravis: aktuelle Antikörperdiagnostik und Aspekte zum therapierefraktären Verlauf

“…Antikörper gegen den intrazellulären Ryanodin-Rezeptor sind ebenso wie Titin-Ak hochverdächtig auf eine thymomassoziierte Myasthenie [29]. Sie können aber auch seltener bei der LOMG ohne Thymome vorkommen [32]. Sie richten sich gegen den Kalziumkanal des sarkoplasmatischen Retikulums.…”