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Serum amyloid A facilitates expansion of CD4+ T cell and CD19+ B cell subsets implicated in the severity of myasthenia gravis patients
Authors:Xiaoyu Huang  Xueting An  Xue Gao  Ningning Wang  Jia Liu  Yong Zhang  Guoyan Qi  Chao Zhang
Affiliation:1. Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China;2. Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China

Contribution: Writing - original draft, Methodology, Data curation;3. Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China

Contribution: Methodology, ​Investigation, Data curation;4. Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China

Contribution: Methodology, Formal analysis;5. Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China

Contribution: Formal analysis, Methodology;6. Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China

Contribution: Formal analysis, Methodology;7. Center of Treatment of Myasthenia Gravis Hebei Province, First Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, China

Contribution: Writing - review & editing, Visualization

Abstract:Serum amyloid A (SAA) is a clinically useful inflammatory marker involved in the pathogenesis of autoimmune diseases. This study aimed to explore the SAA levels in a cohort of patients with myasthenia gravis (MG) in relation to disease-related clinical parameters and myasthenic crisis (MC) and elucidate the effects of SAA on immune response. A total of 82 MG patients including 50 new-onset MG patients and 32 MC patients were enrolled in this study. Baseline data and laboratory parameters of all enrolled MG patients were routinely recorded through electronic medical systems. SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. CD4+ T and CD19+ B cell subsets were analyzed by flow cytometry. In vitro, human recombinant SAA (Apo-SAA) was applied to stimulate peripheral blood mononuclear cells (PBMCs) from MG patients to observe the effect on T and B cell differentiation. Our results indicated that SAA levels in new-onset MG patients were higher than those in controls and were positively correlated with QMG score, MGFA classification, plasmablast cells, IL-6, and IL-17 levels. Subgroup analysis revealed that SAA levels were increased in generalized MG (GMG) patients than in ocular MG (OMG), as well as elevated in late-onset MG (LOMG) than in early-onset MG (EOMG) and higher in MGFA III/IV compared with MGFA I/II. The ROC curve demonstrated that SAA showed good diagnostic value for MC, especially when combined with NLR. In vitro, Apo-SAA promoted the Th1 cells, Th17 cells, plasmablast cells, and plasma cells differentiation in MG PBMCs. The present findings suggested that SAA was increased in MG patients and promoted expansion of CD4+ T cell and CD19+ B cell subsets, which implicated in the severity of MG patients.
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Keywords:B cell subgroups  disease severity  myasthenia gravis  myasthenic crisis  serum amyloid A  T helper cell subgroups
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