Immunoregulatory Cells in Myasthenia Gravis

Abstract

Myasthenia gravis (MG) is a T cell-dependent, B-cell mediated autoimmune disease caused by antibodies against the nicotinic acetylcholine receptor or other components of the post-synaptic muscle endplate at the neuromuscular junction. These specific antibodies serve as excellent biomarkers for diagnosis, but do not adequately substitute for clinical evaluations to predict disease severity or treatment response. Several immunoregulatory cell populations are implicated in the pathogenesis of MG. The immunophenotype of these populations has been well-characterized in human peripheral blood. CD4+FoxP3+ regulatory T cells (Tregs) are functionally defective in MG, but there is a lack of consensus on whether they show numerical perturbations. Myeloid-derived suppressor cells (MDSCs) have also been explored in the context of MG. Adoptive transfer of CD4+FoxP3+ Tregs or MDSCs suppresses ongoing experimental autoimmune MG (EAMG), a rodent model of MG, suggesting a protective role of both populations in this disease. An imbalance between follicular Tregs and follicular T helper cells is found in untreated MG patients, correlating with disease manifestations. There is an inverse correlation between the frequency of circulating IL-10–producing B cells and clinical status in MG patients. Taken together, both functional and numerical defects in various populations of immunoregulatory cells in EAMG and human MG have been demonstrated, but how they relate to pathogenesis and whether these cells can serve as biomarkers of disease activity in humans deserve further exploration.

Effect of Fufang Huangqi Decoction on the Gut Microbiota in Patients With Class I or II Myasthenia Gravis

“…This regulation is related to some immune cells, and the findings suggest that beneficial gut microbiota can promote immune balance (27,28). Although the pathogenesis of MG is still not clear, many studies have shown that its pathogenesis is associated with cell-mediated immunity (29,30). Studies have proposed that specific changes in microbial compositions have a substantial impact on the number of Foxp3+ CD4+ Tregs and the T cell receptor pool and that an imbalance of Foxp3+ CD4+ Tregs may induce the excessive production of AChR antibodies.…”

Oral Microbiota Profile in a Group of Anti-AChR Antibody–Positive Myasthenia Gravis Patients

“…Streptococcus regulates PPARγ and its ligand 15D-PGJ2 by activating PPARγ and inhibiting certain pathways or immune cell functions. PPARγ is involved in regulating the proliferation and differentiation of immune cells including FoxP3+ CD4+ Treg cells ( 17 ), which maintain self-tolerance and immune homeostasis and play a key role in the occurrence of MG ( 13 , 23 , 24 ). Rothia species are opportunistic pathogens associated with various infections in immunocompromised and immunocompetent individuals.…”

Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells

“…This association is also evident in MG-T patients and is characterized by an increase in CD4+ T cells and Th17 cells and a decrease in Treg cells (92). As the number of Tregs increases in MG-T patients upon immunosuppressive treatment (94) and the number of Th17 cells correlates with the severity of the disease (95), the alteration of XLOC_003810 expression could enhance the imbalance in the Th17/Treg ratio, favoring the pathogenetic mechanism. Moreover, the discrimination between patients with MG with or without thymoma is also determined by the different hypomethylation and hypermethylation levels associated with the aberrant expression of lncRNAs.…”