Dataset Information

TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitis.

ABSTRACT:

Background

Ankylosing spondylitis (AS) is a chronic inflammatory disease with worldwide high prevalence. Although AS is strongly associated with HLA-B27 MHC-I antigen presentation, the role played by αβ T cells in AS remains elusive.

Methods

Utilizing TCRβ repertoire sequencing and bioinformatics tools developed in house, we analyzed overall TCR repertoire structures and antigen-recognizing CDR3 motifs in AS patients with different disease activities.

Findings

We found that disease progression is associated with both CD4+ and CD8+ T cell oligo-clonal expansion, which suggests that αβ T cell activation may mediate AS disease progression. By developing a bioinformatics platform to dissect antigen-specific responses, we discovered a cell population consisting of both CD4+ and CD8+ T cells expressing identical TCRs, herein termed CD4/8 T cells. CD4/8 clonotypes were highly enriched in the spondyloarthritic joint fluid of patients, and their expansion correlated with the activity of disease.

Interpretation

These results provide evidence on the T cell clone side to reveal the potential role of CD4/8 T cells in the etiology of AS development.

SUBMITTER: Zheng M

PROVIDER: S-EPMC6796593 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitis.

Zheng Ming M Zhang Xin X Zhou Yinghui Y Tang Juan J Han Qing Q Zhang Yang Y Ni Qingshan Q Chen Gang G Jia Qingzhu Q Yu Haili H Liu Siqi S Robins Elizabeth E Jiang Ning Jenny NJ Wan Ying Y Li Qi-Jing QJ Chen Zhi-Nan ZN Zhu Ping P

EBioMedicine 20190830

<h4>Background</h4>Ankylosing spondylitis (AS) is a chronic inflammatory disease with worldwide high prevalence. Although AS is strongly associated with HLA-B27 MHC-I antigen presentation, the role played by αβ T cells in AS remains elusive.<h4>Methods</h4>Utilizing TCRβ repertoire sequencing and bioinformatics tools developed in house, we analyzed overall TCR repertoire structures and antigen-recognizing CDR3 motifs in AS patients with different disease activities.<h4>Findings</h4>We found that ...[more]

PMID: 31477563

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Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.

Dataset Information

TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitis.

Background

Methods

Findings

Interpretation

Publications

TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitis.

Similar Datasets

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