1. Academic Validation
  2. Diabetes mellitus aggravates humoral immune response in myasthenia gravis by promoting differentiation and activation of circulating Tfh cells

Diabetes mellitus aggravates humoral immune response in myasthenia gravis by promoting differentiation and activation of circulating Tfh cells

  • Clin Immunol. 2022 Oct 18;109141. doi: 10.1016/j.clim.2022.109141.
Tao Li 1 Chun-Lin Yang 2 Tong Du 2 Peng Zhang 2 Yang Zhou 3 Xiao-Li Li 2 Cong-Cong Wang 2 Ying Liu 2 Heng Li 2 Min Zhang 2 Rui-Sheng Duan 4
Affiliations

Affiliations

  • 1 Department of Neurology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250014, China.
  • 2 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, China; Shandong Institute of Neuroimmunology, Jinan, Shandong 250014, China; Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, Shandong 250014, China.
  • 3 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, China.
  • 4 Department of Neurology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250014, China; Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, China; Shandong Institute of Neuroimmunology, Jinan, Shandong 250014, China; Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, Shandong 250014, China. Electronic address: ruisheng_duan@163.com.
Abstract

Myasthenia gravis (MG) is a T-cell-dependent, antibody-mediated autoimmune disease. Diabetes mellitus (DM) is a chronic Metabolic Disease characterized by hyperglycemia and emerging evidence indicates its profound impacts on the immune homeostasis. Previous studies and our data showed DM might serve as an independent risk factor of MG, yet the underlying immune and molecular mechanisms remain to be addressed. Our study observed that circulating Tfh (cTfh) cells were increased in MG patients with DM and expressed a high level of ICOS. Besides, positive correlations between activated cTfh cells and plasmablasts were documented. Further studies demonstrated hyperglycemia promoted the differentiation and activation of Tfh cells which, in turn, caused abnormal plasmablasts differentiation and antibody secretion through the mTOR signaling pathway. These results indicated DM might aggravate the aberrant humoral immunity in MG patients by augmenting Tfh cells differentiation and function and tight glycemic control might be beneficial for MG patients with DM.

Keywords

Circulating follicular helper T (Tfh) cells; Diabetes mellitus; Hyperglycemia; Mechanistic target of rapamycin (mTOR) signaling; Myasthenia gravis.

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