Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Linsley PS 

PROVIDER: S-EPMC6477779 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Linsley Peter S PS   Greenbaum Carla J CJ   Rosasco Mario M   Presnell Scott S   Herold Kevan C KC   Dufort Matthew J MJ  

Genes and immunity 20180621 4


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 w  ...[more]

Similar Datasets

2018-12-05 | GSE112594 | GEO
| PRJNA448424 | ENA
| S-EPMC5896673 | biostudies-literature
| S-EPMC10981820 | biostudies-literature
| S-EPMC6889356 | biostudies-literature
| S-EPMC8816751 | biostudies-literature
2012-06-01 | GSE33440 | GEO
2012-05-31 | E-GEOD-33440 | biostudies-arrayexpress
| S-EPMC4175518 | biostudies-literature