title: Inhibition of increased circulating Tfh cell by anti-CD20 monoclonal antibody in patients with type 1 diabetes.
abstract: OBJECTIVE
  Follicular helper T (Tfh) cells exert an important role in autoimmune diseases. Whether it might be involved in type 1 diabetes (T1D) is unknown. Our aim was to investigate the role of Tfh cells in patients with T1D and the effect of anti-CD20 monoclonal antibody (rituximab) on Tfh cells from T1D patients.
  
  
  METHODS
  Fifty-four patients with T1D and 37 healthy controls were enrolled in the current study. 20 of those patients were treated with rituximab. The frequencies of circulating CD4(+)CXCR5(+)ICOS(+)T cells were analyzed by flow cytometry. The serum autoantibodies were detected by radioligand assay. The levels of IL-21, IL-6 and BCL-6 were assessed using ELISA and/or real-time PCR.
  
  
  RESULTS
  Increased frequencies of circulating Tfh cells together with enhanced expression of IL-21 were detected in patients. The correlation between the frequencies of circulating Tfh cells and the serum autoantibodies or C-peptide level was comfirmed. After rituximab therapy, follow-up analysis demonstrated that the frequencies of circulating Tfh cell and serum IA2A were decreased. The levels of IL-21, IL-6 and Bcl-6 mRNA were decreased after treatment. Furthermore, beta cell function in 10 of 20 patients was improved.
  
  
  CONCLUSIONS
  These data indicate Tfh cells may participate in the T1D-relatede immune responses and B cells might play a role in the development of Tfh responses in the disease progression.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Xu
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Heng
authors.initials: H
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D054380:Receptors, CXCR5 / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D060889:Inducible T-Cell Co-Stimulator Protein; D015850:Interleukin-6; D007378:Interleukins; D054380:Receptors, CXCR5; D000098546:Interleukin-21