RESEARCH - Alterations of the synovial T cell repertoire in anti-CCP-positive RA

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Arthritis Rheum. 2009 Jun 29;60(7):1944-1956.

Alterations of the synovial T cell repertoire in anti-citrullinated

protein antibody-positive rheumatoid arthritis.

Cantaert T, Brouard S, Thurlings RM, Pallier A, Salinas GF, Braud C,

Klarenbeek PL, de Vries N, Zhang Y, Soulillou JP, Tak PP, Baeten D.

Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

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 ACPA-seropositive RA.

PMID: 19565497

http://www.ncbi.nlm.nih.gov/pubmed/19565497

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