T cell receptor V beta gene bias in rheumatoid arthritis.

Jenkins, R N; Nikaein, Afzal; Zimmermann, Adriana Fontes; Meek, Katheryn; Lipsky, Peter E.

doi:10.1172/jci116886

Cited by 115 publications

(60 citation statements)

References 53 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, in this study, we did not detect skewed BV17 and other BV genes that were described in Caucasian RA patients. [19][20][21][22][23] The observations have raised the possibility that in this study, overexpression of BV16 and lack of skewed BV17 and some other BV genes described in other reports may be characteristically associated with Chinese RA patients, while BV14 skewing is common to both Caucasian and Chinese patients with RA. Such discrepancies in BV gene skewing may be attributable to both genetic background (eg HLA genes) and environmental factors of geographic significance.…”

Section: Discussionsupporting

confidence: 49%

“…[19][20][21][22][23] Analysis of CDR3 of overexpressed BV genes has revealed some clonotypes that only exist in rheumatoid synovium but not peripheral T cells, suggesting T-cell clonal expansion in the affected joints in RA. [24][25][26] However, clonality and TCR BV gene usage of infiltrating T cells in RA SF or membranes are relatively heterogeneous, which complicates BV gene analysis using regular or semiquantitative PCR.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Sun

Nie²,

et al. 2005

Genes Immun

View full text Add to dashboard Cite

T-lymphocytes play an important role in rheumatoid arthritis (RA). In this study, we evaluated the hypothesis that common T-cell receptor (TCR) structural features may exist among infiltrating T cells of different RA patients, if the TCR repertoire is shaped by interaction with common self or microbial antigens in the context of susceptible HLA genes in RA. Synovial lesion tissue (ST), synovial fluid (SF) and blood specimens from RA patients and controls were analyzed for TCR V gene repertoire by real-time PCR. There was highly skewed BV14 and BV16 usage in synovial T cells of RA as opposed to those of controls, which was accompanied with a trend for correlation between skewed BV16 and DRB1*0405. Immunoscope analysis of the V-D-J region of ST-derived T cells demonstrated oligoclonal and polyclonal expansion of BV14 þ and BV16 þ T cells. Detailed characterization using specific BV and BJ primers further revealed common clonotypes combining the same BV14/BV16, BJ and CDR3 length. DNA cloning and sequence analysis of the clonotypes confirmed identical CDR3 sequences and common CDR3 sequence motifs among different RA patients. The findings are important in the understanding of BV gene skewing and CDR3 structural characteristics among synovial infiltrating T cells of RA.

show abstract

Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Sun

Nie²,

et al. 2005

Genes Immun

View full text Add to dashboard Cite

show abstract

“…Second, this skewing is a primary event, rather than merely a consequence of inflamma- tion, since the unaffected siblings of RA patients also display expanded T cell clonotypes (46,47). Third, although alterations have been noted in the peripheral compartment (48), they are more pronounced in the joint, are similar in different joints in the same patient, and are stable over time (49,50). Finally, the ability to transfer disease to SCID mice by injection of RA synovial T lymphocytes suggests a pathogenic role for these cells (51).…”

Section: Discussionmentioning

confidence: 99%

Alterations of the synovial T cell repertoire in anti–citrullinated protein antibody–positive rheumatoid arthritis

Cantaert¹,

Brouard²,

Thurlings³

et al. 2009

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. The association of HLA-DRB1 alleles with anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) suggests the potential involvement of T lymphocytes in ACPA-seropositive disease. The purpose of this study was to investigate this hypothesis by systematic histologic and molecular analyses of synovial T cells in ACPA؉ versus ACPA-RA patients.Methods. Synovial biopsy samples were obtained from 158 RA patients. Inflammation was determined histologically and immunohistochemically. RNA was extracted from peripheral blood mononuclear cells and synovial tissues obtained from 11 ACPA؉ RA patients, 7 ACPA-RA patients, and 10 spondylarthritis (SpA) patients (arthritis controls). T lymphocyte clonality was studied by combined quantitative and qualitative T cell receptor CDR3 length distribution (LD) analysis and direct sequencing analysis.Results. ACPA؉ and ACPA-RA patients were similar at both the clinical and histologic levels. At the molecular level, however, patients with ACPA؉ synovitis displayed a marked elevation of qualitative CDR3 LD alterations as compared with those with ACPA-synovitis and with the SpA controls. These differences in CDR3 LD were not observed in the peripheral blood, indicating a selective recruitment and/or local expansion of T cells in the synovial compartment. The CDR3 LD alterations reflected true monoclonal or oligoclonal expansions, as confirmed by direct sequencing of the T cell receptor. The CDR3 LD alterations in RA synovium did not correlate with B cell clonal expansions but were inversely associated with synovial lymphoid neogenesis.Conclusion. The T cell repertoire is specifically restricted in RA patients with ACPA؉ synovitis. Whereas the origin and role of these clonal alterations remain to be determined, our data suggest the preferential involvement of T lymphocytes in ACPAseropositive RA.

show abstract

“…It is important that family studies not be confused with analyses of V, expression in RA (5). Family studies deal with germline genes in or near the TCR complex, while expression studies analyze the somatically rearranged T cell receptor repertoire.…”

Section: Discussionmentioning

confidence: 99%

The role of t cell receptor β chain genes in susceptibility to rheumatoid arthritis

McDermott

Kastner

Holloman

et al. 1995

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To evaluate the role of the T cell receptor /3 chain locus (TCRB) in genetic susceptibility to rheumatoid arthritis (RA).Methods. Twenty-eight multiplex RA families were recruited from 3 rheumatology outpatient departments. All members were genotyped for a highly informative microsatellite (Vpd.7), a V d 2 . 2 SSCP marker, and a biallelic C , restriction fragment length polymorphism. Data were analyzed by the SIBPAL program to assess identity-by-descent in affected sib-pairs.Results. Using the Vp12.2 marker, there was suggestive evidence of increased sib-pair sharing (P = 0.005) in affected offspring (a P value of 0.001 is generally

show abstract

T cell receptor V beta gene bias in rheumatoid arthritis.

Cited by 115 publications

References 53 publications

Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Alterations of the synovial T cell repertoire in anti–citrullinated protein antibody–positive rheumatoid arthritis

The role of t cell receptor β chain genes in susceptibility to rheumatoid arthritis

Contact Info

Product

Resources

About