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.
Highlights
Myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness and fatigue [1, 2]
The study showed a positive correlation between circulating Tfh cell frequency and serum anti-acetylcholine receptors (AChRs) antibody titer in these patients [110]. In line with these clinical studies, experimental autoimmune MG (EAMG) mice have a higher frequency of splenic CD4+CXCR5+programmed death-1 (PD-1)+ Tfh cells than controls, and their Tfh cell frequency is positively correlated with the concentration of antiAChR antibodies in serum [111]. All these findings collectively suggest that the frequency of circulating Tfh cells reflects disease activity in AChR+ MG
- Functional defect is associated with reduced forkhead box P3 (FoxP3) expression and MG pathogenesis; - Decreased FoxP3 expression correlates with attenuated signal transducer and activator of transcription-5 (STAT5) signaling; - Numerical correlation remains controversial; - Adoptive transfer treats EAMG
Summary
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. 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
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