Inhibition of increased circulating Tfh cell by anti-CD20 monoclonal antibody in patients with type 1 diabetes

PLoS One. 2013 Nov 20;8(11):e79858. doi: 10.1371/journal.pone.0079858. eCollection 2013.

Abstract

Objectives: 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.

Patients and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD20 / immunology*
  • Child
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism*
  • Female
  • Humans
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Interleukin-6 / metabolism
  • Interleukins / metabolism
  • Male
  • Real-Time Polymerase Chain Reaction
  • Receptors, CXCR5 / metabolism
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antigens, CD20
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-6
  • Interleukins
  • Receptors, CXCR5
  • interleukin-21

Grant support

The study was supported by grants from the National Natural Science Foundation of China (number 30971405, 81270897) and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.