Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Inhibition of increased circulating Tfh cell by anti-CD20 monoclonal antibody in patients with type 1 diabetes (#130)

Xinyu Xu 1 , Yun Shi 1 , Yun Cai 1 , Qingqing Zhang 1 , Fan Yang 1 , Heng Chen 1 , Yong Gu 1 , Mei Zhang 1 , Liping Yu 2 , Tao Yang 1
  1. The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
  2. Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA

Objectives: Follicular helper T (Tfh) cells exert an important role in the autoimmune diseases. Whether it might involve 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 conformed. 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 the possible involvement of Tfh cells in the disease progression of T1D and B cells might play a role in the development of Tfh responses. It points to a potential therapeutic strategy in T1D.