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2016 ; 68
(7
): 1758-68
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Next-Generation Sequencing Reveals Restriction and Clonotypic Expansion of Treg
Cells in Juvenile Idiopathic Arthritis
#MMPMID26815131
Henderson LA
; Volpi S
; Frugoni F
; Janssen E
; Kim S
; Sundel RP
; Dedeoglu F
; Lo MS
; Hazen MM
; Beth Son M
; Mathieu R
; Zurakowski D
; Yu N
; Lebedeva T
; Fuhlbrigge RC
; Walter JE
; Nee Lee Y
; Nigrovic PA
; Notarangelo LD
Arthritis Rheumatol
2016[Jul]; 68
(7
): 1758-68
PMID26815131
show ga
OBJECTIVE: Treg cell-mediated suppression of Teff cells is impaired in juvenile
idiopathic arthritis (JIA); however, the basis for this dysfunction is
incompletely understood. Animal models of autoimmunity and immunodeficiency
demonstrate that a diverse Treg cell repertoire is essential to maintain Treg
cell function. The present study was undertaken to investigate the Treg and Teff
cell repertoires in JIA. METHODS: Treg cells (CD4+CD25+CD127(low) ) and Teff
cells (CD4+CD25-) were isolated from peripheral blood and synovial fluid obtained
from JIA patients, healthy controls, and children with Lyme arthritis. Treg cell
function was measured in suppressive assays. The T cell receptor ? chain (TRB)
was amplified by multiplex polymerase chain reaction and next-generation
sequencing was performed, with amplicons sequenced using an Illumina HiSeq
platform. Data were analyzed using ImmunoSEQ, International ImMunoGeneTics
system, and the Immunoglobulin Analysis Tools. RESULTS: Compared to findings in
controls, the JIA peripheral blood Treg cell repertoire was restricted, and
clonotypic expansions were found in both blood and synovial fluid Treg cells.
Skewed usage and pairing of TRB variable and joining genes, including overuse of
gene segments that have been associated with other autoimmune conditions, was
observed. JIA patients shared a substantial portion of synovial fluid Treg cell
clonotypes that were private to JIA and not identified in Lyme arthritis.
CONCLUSION: We identified restriction and clonotypic expansions in the JIA Treg
cell repertoire with sharing of Treg cell clonotypes across patients. These
findings suggest that abnormalities in the Treg cell repertoire, possibly
engendered by shared antigenic triggers, may contribute to disease pathogenesis
in JIA.