PLoS By Category | Recent PLoS Articles

Diabetes and Endocrinology - Hematology - Immunology


Acute Response of Peripheral Blood Cell to Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetic Patient
Published: Wednesday, February 22, 2012
Author: Xiaofang Zhang et al.

by Xiaofang Zhang, Lei Ye, Jiong Hu, Wei Tang, Ruixin Liu, Minglan Yang, Jie Hong, Weiqing Wang, Guang Ning, Weiqiong Gu

Objective

Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) was the first therapeutic approach that can improve ß cell function in type 1 diabetic (T1D) patients. This study was designed to investigate the potential mechanisms involved.

Design and methods

We applied AHST to nine T1D patients diagnosed within six months and analyzed the acute responses in peripheral blood for lymphocyte subpopulation as well as for genomic expression profiling at the six-month follow-up.

Results

We found six patients obtained insulin free (IF group) and three remained insulin dependent (ID group); C-peptide production was significantly higher in IF group compared to ID group. The acute responses in lymphocytes at six-month follow-up include declined CD3+CD4+, CD3+CD8+ T cell population and recovered B cell, NK cell population in both groups but with no significant differences between the two groups; most immune-related genes and pathways were up-regulated in peripheral blood mononuclear cell (PBMC) of both groups while none of transcription factors for immune regulatory component were significantly changed; the IF group demonstrated more AHST-modified genetic events than the ID group and distinct pattern of top pathways, co-expression network as well as ‘hub’ genes (eg, TCF7 and GZMA) were associated with each group.

Conclusions

AHST could improve the islet function in newly diagnosed T1D patients and elimination of the islet specific autoreactive T cells might be one of the mechanisms involved; T1D patients responded differently to AHST possibly due to the distinct transcriptional events occurring in PBMC.

Trial Registration

ClinicalTrials.gov NCT00807651

  More...

 
//-->