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PLoS One. 2012;7(2):e31887. doi: 10.1371/journal.pone.0031887. Epub 2012 Feb 22.

Acute response of peripheral blood cell to autologous hematopoietic stem cell transplantation in type 1 diabetic patient.

Author information

1
Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, School of Medicine, Shanghai Jiaotong University, Ruijin Hospital, Shanghai, People's Republic of China.

Abstract

OBJECTIVE:

Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) was the first therapeutic approach that can improve β 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.

PMID:
22384093
PMCID:
PMC3285188
DOI:
10.1371/journal.pone.0031887
[Indexed for MEDLINE]
Free PMC Article
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