scholarly journals Collagen-specific T-cell repertoire in blood and synovial fluid varies with disease activity in early rheumatoid arthritis

2008 ◽  
Vol 10 (6) ◽  
pp. R135 ◽  
Author(s):  
Francesco Ria ◽  
Romina Penitente ◽  
Maria De Santis ◽  
Chiara Nicolò ◽  
Gabriele Di Sante ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
T Cell Repertoire ◽  
Cell Repertoire

scholarly journals Characterization of T-Cell Receptor Repertoire in Patients with Rheumatoid Arthritis Receiving Biologic Therapies

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Che-Mai Chang ◽  
Yu-Wen Hsu ◽  
Henry Sung-Ching Wong ◽  
James Cheng-Chung Wei ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Disease Activity ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Therapeutic Effects ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Tcr Repertoire ◽  
Repertoire Diversity

Rheumatoid arthritis (RA) is a systematic autoimmune disease, predominantly causing chronic polyarticular inflammation and joint injury of patients. For the treatment of RA, biologic disease-modifying antirheumatic drugs (bDMARDs) have been used to reduce inflammation and to interfere with disease progression through targeting and mediating the immune system. Although the therapeutic effects of bDMARDs in RA patients have been widely reported, whether these drugs also play important roles in T-cell repertoire status is still unclear. We therefore designed the study to identify the role of T-cell repertoire profiles in RA patients with different types of bDMARD treatments. A high-throughput sequencing approach was applied to profile the T-cell receptor beta chain (TCRB) repertoire of circulating T lymphocytes in eight patients given adalimumab (anti-TNF-α) with/without the following use of either rituximab (anti-CD20) or tocilizumab (anti-IL6R). We subsequently analyzed discrepancies in the clonal diversity and CDR3 length distribution as well as usages of the V and J genes of TCRB repertoire and interrogated the association between repertoire diversity and disease activities followed by the treatment of bDMARDs in these RA patients. All groups of patients showed well-controlled DAS28 scores (<2.6) after different treatment regimens of drugs and displayed no significant statistical differences in repertoire diversity, distribution of CDR3 lengths, and usage of V and J genes of TCRB. Nonetheless, a trend between overall TCRB repertoire diversity and disease activity scores in all bDMARD-treated RA patients was observed. Additionally, age was found to be associated with repertoire diversity in RA patients treated with bDMARDs. Through the profiling of the TCR repertoire in RA patients receiving different biologic medications, our study indicated an inverse tendency between TCR repertoire diversity and disease activity after biologic treatment in RA patients.

scholarly journals Sex-based differences in association between circulating T cell subsets and disease activity in untreated early rheumatoid arthritis patients

2018 ◽  
Vol 20 (1) ◽  
Author(s):  
Jonathan Aldridge ◽  
Jayesh M. Pandya ◽  
Linda Meurs ◽  
Kerstin Andersson ◽  
Inger Nordström ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
T Cell Subsets

scholarly journals Perturbation of the T cell repertoire in rheumatoid arthritis

1998 ◽  
Vol 95 (24) ◽  
pp. 14447-14452 ◽  
Author(s):  
U. G. Wagner ◽  
K. Koetz ◽  
C. M. Weyand ◽  
J. J. Goronzy
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire

The shared susceptibility epitope of HLA-DR4 binds citrullinated self-antigens and the TCR

2021 ◽  
Vol 6 (58) ◽  
pp. eabe0896
Author(s):  
Jia Jia Lim ◽  
Claerwen M. Jones ◽  
Tiing Jen Loh ◽  
Yi Tian Ting ◽  
Pirooz Zareie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Receptor ◽  
Posttranslational Modification ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Increased Risk ◽  
Β Chain

Individuals expressing HLA-DR4 bearing the shared susceptibility epitope (SE) have an increased risk of developing rheumatoid arthritis (RA). Posttranslational modification of self-proteins via citrullination leads to the formation of neoantigens that can be presented by HLA-DR4 SE allomorphs. However, in T cell–mediated autoimmunity, the interplay between the HLA molecule, posttranslationally modified epitope(s), and the responding T cell repertoire remains unclear. In HLA-DR4 transgenic mice, we show that immunization with a Fibβ-74cit69-81 peptide led to a population of HLA-DR4Fibβ-74cit69-81 tetramer+ T cells that exhibited biased T cell receptor (TCR) β chain usage, which was attributable to selective clonal expansion from the preimmune repertoire. Crystal structures of pre- and postimmune TCRs showed that the SE of HLA-DR4 represented a main TCR contact zone. Immunization with a double citrullinated epitope (Fibβ-72,74cit69-81) altered the responding HLA-DR4 tetramer+ T cell repertoire, which was due to the P2-citrulline residue interacting with the TCR itself. We show that the SE of HLA-DR4 has dual functionality, namely, presentation and a direct TCR recognition determinant. Analogous biased TCR β chain usage toward the Fibβ-74cit69-81 peptide was observed in healthy HLA-DR4+ individuals and patients with HLA-DR4+ RA, thereby suggesting a link to human RA.

scholarly journals Collagen Specific T-Cell Repertoire and HLA-DR Alleles: Biomarkers of Active Refractory Rheumatoid Arthritis

EBioMedicine ◽  
2015 ◽  
Vol 2 (12) ◽  
pp. 2037-2045 ◽  
Author(s):  
Gabriele Di Sante ◽  
Barbara Tolusso ◽  
Anna Laura Fedele ◽  
Elisa Gremese ◽  
Stefano Alivernini ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Hla Dr ◽  
Refractory Rheumatoid Arthritis

scholarly journals POS0004 T-CELL REPERTOIRE OF SYNOVIAL FLUID IN SPONDYLOARTHROPATHIES EXHIBITS HALLMARKS OF HLA-DEPENDENT CLONAL EXPANSIONS AND REMAINS STABLE OVER 1.5 YEARS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 204.2-204
Author(s):  
E. Komech ◽  
A. Koltakova ◽  
E. Shmidt ◽  
A. Barinova ◽  
M. Salnikova ◽  
...  
Keyword(s):  
T Cells ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
T Cell ◽  
Synovial Fluid ◽  
Mononuclear Cells ◽  
Cdna Libraries ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Clonal Composition

Background:Different studies show involvement of T-cells in pathogenesis of spondyloarthropathies (SpAs) - a group of rheumatic diseases strongly associated with presence of several MHC-I alleles (HLA-B*27, -B*38, -B*39, etc). Recently we and others identified a specific T-cell receptor motif in blood and synovial fluid of HLA-B*27+ AS patients that reinforces the “arthritogenic peptide” hypothesis of AS pathogenesis [1-2]. However, common characteristics of clonal T-cell repertoire of synovial fluid in SpAs remain poorly investigated.Objectives:We aimed to investigate synovial fluid T-cell repertoires of SpA patients with different HLA-genotypes and stability of the clonal composition in recurring flares of the disease.Methods:Mononuclear cells were isolated from paired peripheral blood (PB) and synovial fluid (SF) samples of SpA patients (ankylosing spondylitis and psoriatic arthritis, n=27). For 3 patients additional SF samples were collected during relapse of the synovitis (after 9-15 months). CD4 and CD8 T-cells were isolated by immunomagnetic separation. Deep sequencing of UMI-tagged TCR beta cDNA libraries was used to accurately reconstruct clonal T-cell repertoires. HLA class I and II were typed for each donor using an in-house NGS-based system.Results:We observed restricted T-cell clonal composition in synovial fluid: on average only 6% of PB T-cell clonotypes were detected in SF of the same donor. T-cell repertoires of both CD4 and CD8 SF subsets compared to PB were highly oligoclonal (index Gini PB vs SF: CD4 0.36±0.10 vs 0.68±0.08, CD8 0.57±0.17 vs 0.81±0.12) in all patients. Number of identical amino acid CDR3 sequences between two repertoires correlated with the number of identical HLA-alleles for the donors. This trend was exhibited more strikingly in SF compared to PB, suggesting that common antigens may play a role in accumulation of identical T-cell clonotypes in the inflamed joint. Using several bioinformatic approaches we identified groups of highly similar SF clonotypes linked to HLA-B*27 and/or HLA-B*38 genotype.Total SF repertoires of relapsing synovitis of the same donor showed huge clonal overlap, and the most frequent clonotypes remained almost unchanged (Morisita’s overlap index for total SF repertoires 0.69±0.26; for top 1000 clonotypes 0.79±0.19, n=3).Conclusion:We report HLA-dependent sharing of identical and similar T-cell clonotypes in SF of patients with ankylosing spondylitis and psoriatic arthritis and high stability of SF repertoire during several flares that support antigen-driven accumulation of T-cells in the site of inflammation.References:[1]Komech EA et al. Rheumatology (Oxford). 2018;57(6):1097-1104.[2]Faham M et al. Arthritis Rheumatol. 2016;11(10):300-308.Acknowledgements:The work is supported by Russian Science Foundation grant №20-75-00041.Disclosure of Interests:None declared.

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