PMID- 30674904
OWN - NLM
STAT- MEDLINE
DCOM- 20200624
LR  - 20200624
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Jan 23
TI  - Comprehensive Analysis of TCR-beta Repertoire in Patients with Neurological 
      Immune-mediated Disorders.
PG  - 344
LID - 10.1038/s41598-018-36274-7 [doi]
LID - 344
AB  - In this study we characterized the TCR repertoire profiles in patients with 
      chronic progressive inflammatory neurological disorders including HAM/TSP, 
      associated with human T-cell lymphotropic virus type I (HTLV-I) infection, and 
      multiple sclerosis (MS), an inflammatory, demyelinating disease of the CNS of 
      unknown etiology. We hypothesized that a T-cell receptor (TCR) clonal repertoire 
      'signature' could distinguish HAM/TSP patients from healthy controls, as well as 
      from patients with a more heterogeneous CNS-reactive inflammatory disease such as 
      MS. In this study, we applied an unbiased molecular technique - unique molecular 
      identifier (UMI) library-based strategy to investigate with high accuracy the TCR 
      clonal repertoire by high throughput sequencing (HTS) technology. cDNA-TCR 
      beta-chain libraries were sequenced from 2 million peripheral mononuclear cells 
      (PBMCs) in 14 HAM/TSP patients, 34 MS patients and 20 healthy controls (HC). 
      While HAM/TSP patients showed a higher clonal T-cell expansion compared to MS and 
      HC, increase of the TCR clonal expansion was inversely correlated with the 
      diversity of TCR repertoire in all subjects. In addition, longitudinal analysis 
      of TCR repertoires from HAM/TSP patients demonstrated a correlation of the TCR 
      clonal expansion with HTLV-I proviral load. Surprisingly, MS patients showed a 
      higher diversity of TCR repertoires than other groups. Despite higher TCR clonal 
      expansions in HAM/TSP patients, no disease-specific TCRs were shared among 
      patients. Only non-shared or "private" TCR repertoires was observed. While no 
      clones that shared the same CDR3 amino acid sequences were seen in either HC or 
      MS patients, there was a cluster of related CDR3 amino acid sequences observed 
      for 18 out of 34 MS patients when evaluated by phylogenetic tree analysis. This 
      suggests that a TCR-repertoire signature may be identified in a subset of 
      patients with MS.
FAU - Alves Sousa, Alessandra de Paula
AU  - Alves Sousa AP
AD  - Neuroimmunology Branch, Viral Immunology Section, National Institute of 
      Neurological Disorder and Stroke, NIH, Bethesda, Maryland, United States.
FAU - Johnson, Kory R
AU  - Johnson KR
AD  - Bioinformatics Section, National Institute of Neurological Disorder and Stroke, 
      NIH, Bethesda, Maryland, United States.
FAU - Ohayon, Joan
AU  - Ohayon J
AD  - Clinical Neuroimmunology Unit, National Institute of Neurological Disorder and 
      Stroke, NIH, Bethesda, Maryland, United States.
FAU - Zhu, Jun
AU  - Zhu J
AUID- ORCID: 0000-0003-4573-8933
AD  - Systems Biology Center, National Heart Lung and Blood Institute, NIH, Bethesda, 
      Maryland, United States.
FAU - Muraro, Paolo A
AU  - Muraro PA
AUID- ORCID: 0000-0002-3822-1218
AD  - Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, 
      United Kingdom.
FAU - Jacobson, Steven
AU  - Jacobson S
AD  - Neuroimmunology Branch, Viral Immunology Section, National Institute of 
      Neurological Disorder and Stroke, NIH, Bethesda, Maryland, United States. 
      jacobsons@ninds.nih.gov.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190123
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Female
MH  - *Genetic Variation
MH  - HTLV-I Infections/*pathology
MH  - Humans
MH  - Leukocytes, Mononuclear/*pathology
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*pathology
MH  - Receptors, Antigen, T-Cell, alpha-beta/*genetics
MH  - Sequence Analysis, DNA
MH  - Time Factors
MH  - Viral Load
MH  - Young Adult
PMC - PMC6344574
COIS- The authors declare no competing interests.
EDAT- 2019/01/25 06:00
MHDA- 2020/06/25 06:00
PMCR- 2019/01/23
CRDT- 2019/01/25 06:00
PHST- 2018/06/28 00:00 [received]
PHST- 2018/10/30 00:00 [accepted]
PHST- 2019/01/25 06:00 [entrez]
PHST- 2019/01/25 06:00 [pubmed]
PHST- 2020/06/25 06:00 [medline]
PHST- 2019/01/23 00:00 [pmc-release]
AID - 10.1038/s41598-018-36274-7 [pii]
AID - 36274 [pii]
AID - 10.1038/s41598-018-36274-7 [doi]
PST - epublish
SO  - Sci Rep. 2019 Jan 23;9(1):344. doi: 10.1038/s41598-018-36274-7.