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Pediatr Diabetes. 2018 Nov;19(7):1229-1237. doi: 10.1111/pedi.12728. Epub 2018 Aug 29.

Comprehensive assessment of T-cell repertoire following autologous hematopoietic stem cell transplantation for treatment of type 1 diabetes using high-throughput sequencing.

Author information

1
Department of Endocrine and Metabolic diseases, Ruijin Hospital, Shanghai Jiao-Tong University, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Shanghai, China.
2
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia.
3
Beijing Genomics Institute, Shenzhen, Guangdong, China.
4
Laboratory for Endocrine & Metabolic Diseases, Institute of Health Science, Shanghai JiaoTong University, School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Abstract

OBJECTIVE:

We aimed to investigate T-cell receptor (TCR) repertoires in type 1 diabetes (T1D) patients receiving autologous hematopoietic stem cell transplantation (AHSCT) treatment.

METHODS:

High-throughput deep TCR beta (TCRB) chain sequencing was performed to assess millions of individual TCRs in five T1D patients receiving AHSCT treatment and another five patients receiving insulin treatment during 12 months of follow-up.

RESULTS:

No significant changes in TCRB sequence reads, complementarity-determining region 3 (CDR3) sequences, or the usage of TCRB VJ gene-segments were observed at 12 months after AHSCT. Compared with the baseline, the usage of TCRB VJ gene-segments at 12 months decreased in the insulin treatment group (1836.4 ± 437.7 vs 2763.6 ± 390.6, P = 0.015), and the change rates were larger than those undergoing AHSCT (-0.62 ± 0.16 vs 0.06 ± 0.45, P = 0.002). Changes in the TCR repertoire were smaller after AHSCT than those with insulin treatment (P = 2.2*10-32 ). TCRBV 7-7/TCRBJ 2-5 was depleted after AHSCT while expanded with insulin treatment. TCRBV 12-4, TCRBV 10-3, TCRBV 12-3/TCRBJ 1-2 were expanded after AHSCT while ablated with insulin treatment.

CONCLUSIONS:

We found that AHSCT is safe without reduction in the diversity of TCR repertoires and TCR repertoires tend to be more stable after AHSCT. Furthermore, these four candidate TCRBV/TCRBJ gene usages on CDR3 regions may act as therapeutic targets and biomarkers.

KEYWORDS:

AHSCT; TCR repertoire; autoimmunity; type 1 diabetes

PMID:
30022578
DOI:
10.1111/pedi.12728
[Indexed for MEDLINE]

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