Elevated T cell levels in peripheral blood predict poor clinical response following rituximab treatment in new-onset type 1 diabetes

Genes Immun. 2019 Apr;20(4):293-307. doi: 10.1038/s41435-018-0032-1. Epub 2018 Jun 21.


Biologic treatment of type 1 diabetes (T1D) with agents including anti-CD3 (otelixizumab and teplizumab), anti-CD20 (rituximab), LFA3Ig (alafacept), and CTLA4Ig (abatacept) results in transient stabilization of insulin C-peptide, a surrogate for endogenous insulin secretion. With the goal of inducing more robust immune tolerance, we used systems biology approaches to elucidate mechanisms associated with C-peptide stabilization in clinical trial blood samples from new-onset T1D subjects treated with the B cell-depleting drug, rituximab. RNA sequencing (RNA-seq) analysis of whole-blood samples from this trial revealed a transient increase in heterogeneous T cell populations, which were associated with decreased pharmacodynamic activity of rituximab, increased proliferative responses to islet antigens, and more rapid C-peptide loss. Our findings illustrate complexity in hematopoietic remodeling that accompanies B cell depletion by rituximab, which impacts and predicts therapeutic efficacy in T1D. Our data also suggest that a combination of rituximab with therapy targeting CD4 + T cells may be beneficial for T1D subjects.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Female
  • Humans
  • Immunologic Factors / therapeutic use*
  • Lymphocyte Count
  • Male
  • Rituximab / therapeutic use*
  • T-Lymphocytes / cytology*
  • Treatment Outcome


  • Biomarkers
  • Immunologic Factors
  • Rituximab