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OP0222 (Collagen Specific-)T Cell Related Parameters Provide Information for the Management of Rheumatoid Arthritis Patients
  1. G. Di Sante1,
  2. C. Nicolò1,
  3. A.L. Fedele2,
  4. E. Gremese2,
  5. B. Tolusso2,
  6. A. Carbonella2,
  7. M.R. Gigante2,
  8. S.L. Bosello2,
  9. F. Ria1,
  10. G. Ferraccioli2
  1. 1Institute of General Pathology
  2. 2Division Of Rheumatology, Institute Of Rheumatology And Affine Sciences, Catholic University Of The Sacred Heart, Rome, Italy

Abstract

Background The developmental risk of Rheumatoid Arthritis (RA) is strongly linked to HLA-DRB1*04 (DR4) and *01 (DR1). In RA, activated immune cells, as CD4+T cells, B cells, dendritic cells and macrophages infiltrate the synovial tissue. In a previous work, we found that huCollp261-273-specific T cell repertoire analyzed in peripheral blood of DR4+ RA patients was restricted to a limited number of TCR rearrangements. This collagen-specific repertoire appears modulated by disease activity (1). The two most used TCR-beta chains were TRBV25-TRBJ2.2 and TRBV6-4-TRBJ2-3.

Objectives To examine the frequency and the distribution of huCollp261-273-specific T cells and the role of DR alleles in RA patients in order to find new biomarker for the management of the disease.

Methods HLA genotyping was performed using the Innogenetics® kit, following the manufacturer's protocol. TCR repertoire analysis: Peripheral blood mononuclear cells (PBMCs) were purified from whole blood and TCR BV-JB analysis was performed as previously described. (1) Patients: we analyzed 100 samples from RA patients, 57 with a high disease activity (DAS >3.7) and 43 with a low disease activity (DAS≤2.4).

Results The presence of TRBV25-TRBJ2.2 and TRBV6-4-TRBJ2-3 in T cells was significantly associated with disease activity in the group of DR4+ RA patients. The usage of these two receptors described two non-overlapping groups of RA patients, with subjects using TRBV6-4+ displaying a significantly higher disease activity. The combination of TCR usage in DR4+ subjects and of DR haplotypes in RA patients described four distinct responses to treatment with Disease Modifying Antirheumatic Drugs (DMARDs) and biologic agents. Fifty percent of DR4+ TRBV25- patients responded to DMARDs and the remaining responded well to biologic agents; DR4+ TRBV25+ patients failed to respond to DMARDs but displayed a good response to biologic agents and this latter group might therefore be candidate to treatment with biologic agents. In the group of DR4-, DR1- or DR7-patients, the DR11 allele appeared highly enriched in subjects displaying a high disease activity. Accordingly, within the group of DR4-, DR1- DR7- RA patients, we observed that 50% of all patients achieved a good response after DMARDs treatment; among patients non-responder to DMARDs, however, it appeared that DR11+ subjects responded to a lesser extent than DR11- patients to biologic agents.

Conclusions These findings showed that the analysis of collagen specific T cells repertoire and HLA-DR haplotype can provide useful information to a personalized treatment in RA patients.

References

  1. Ria F., et al. Arthritis Research & Therapy, 2008.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.4311

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