Inflamed target tissue provides a specific niche for highly expanded T-cell clones in early human autoimmune disease

Klarenbeek, P L; Hair, Maria J. H. de; Doorenspleet, Marieke E.; Schaik, Barbera D.C. van; Esveldt, Rebecca E. E.; Sande, Marleen G H van de; Cantaert, Tineke; Gerlag, Daniëlle M.; Baeten, Dominique; Kampen, Antoine H. C. van; Baas, Frank; Tak, Paul‐Peter; Vries, Niek de

doi:10.1136/annrheumdis-2011-200612

Cited by 130 publications

(133 citation statements)

References 42 publications

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“…23,96 Recently, a highly expanded, specific T-cell clone has been identified in early RA, which underlines the importance of T-cells in early stage disease. 97 Epigenetic changes in FLS over time may define the different stages of RA after clinical onset of the disease.…”

Section: Early Arthritis and Early Diagnosismentioning

confidence: 99%

Synovial tissue research: a state-of-the-art review

et al. 2017

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The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis (RA). The study of synovial tissue has advanced significantly over a number of decades from arthroplasty, blind needle biopsy and more recently facilitated by arthroscopic and ultrasonographic technology that allows easier visualisation and improves the reliability of obtaining synovial biopsies. The potential for study of pathogenesis, patient stratification, discovery of biomarkers and novel targets, as well as validation of therapy, have all been progressed rapidly in the last decade, facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this review we describe clinical and translational developments in the field of synovial tissue research, outlining current and novel investigative technologies, and highlight their application to advance our understanding of the aforegoing imperatives.3

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Section: Early Arthritis and Early Diagnosismentioning

confidence: 99%

Synovial tissue research: a state-of-the-art review

et al. 2017

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“…These data obtained from CDR3 spectratyping and clone sequencing are considerably limited, and features such as the biased usage of certain TRBVs in T cell repertoire, the highly expressed of certain CDR3 sequences, and base insertion in the CDR3 region need to be further characterized and analyzed with respect to the role they may play in the development of SLE. With the successful application of high-throughput sequencing in analyzing TCR CDR3 repertoire, (Klarenbeek et al 2012;Meier et al 2013;Wu et al 2012) it is now possible to study the relationship between the complete TCR CDR3 repertoire and SLE. This study used Roche 454 highthroughput sequencing to analyze and compare the T cell (mRNA) TCR β-chain CDR3 repertoire from the thymuses and spleens of 1-, 3-, and 5-month-old MRL/lpr mice.…”

Section: Introductionmentioning

confidence: 99%

Composition and variation analysis of TCR β-chain CDR3 repertoire in the thymus and spleen of MRL/lpr mouse at different ages

Zhou

Liu

et al. 2014

Immunogenetics

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T cells play an important role in the onset and progression of systemic lupus erythematosus (SLE), and the biases in T cell receptor beta variable (TRBV) region families and complementarity determining region three (CDR3) composition in SLE patients and mouse models have been widely reported. However, the relationship between the composition and variation in the TCR β-chain CDR3 repertoire and SLE has not been established. Here, we compared and analyzed the thymic and splenic TCR β-chain CDR3 mRNA sequences by Roche 454 high-throughput sequencing from MRL/lpr mice at different ages. Our results indicate that diversity in the TCR CDR3 repertoire from the thymus and spleen from MRL/lpr mouse was significantly decreased with increased age (disease progression) and showed a bias in usage of common TRBV and TRBJ families. The N1 region insertions in the highly expressed CDR3s significantly increased with disease progression. This study provides a new perspective for studying SLE with progression of disease in clonal level of TCR, which may provide a basis for studying the mechanism of the MRL/lpr autoreactive T cells response and tailor an individualized treatment targeting these T cells.

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“…Complementary DNA was synthesized using SuperScript II reverse transcriptase (Invitrogen). Primers were purchased from Biolegio and used in a linear amplification protocol as described previously (30,31). Briefly, a set of 6 V H family primers for all possible BCR V H genes was designed for the first amplification step (details on the primers available upon request from the corresponding author).…”

Section: Methodsmentioning

confidence: 99%

“…Samples were separated using a unique 5-base-long Multiplex Identifier sequence for every sample. After sequencing, data are recovered using a customized BLAT algorithm (30,31).…”

Section: Methodsmentioning

confidence: 99%