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

Gabriele Di Sante, Elisa Gremese, Stefano Alivernini, Francesco Ria, Barbara Tolusso, Anna Laura Fedele, Chiara Nicolo', Gianfranco Ferraccioli

Risultato della ricerca: Contributo in rivistaArticolo in rivista

21 Citazioni (Scopus)

Abstract

Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and associates with HLA-DRB1*04. The Collagen IIp261-273-specific T cell repertoire in the peripheral blood of DR4 + patients at the onset of the disease shows a restricted TCR-beta chain usage among which the most frequent is TRBV25. To define whether this group of DR4-restricted collagen-specific shared T cell could represent markers of active-severe disease and response to therapy, 90 subjects affected by early-RA were enrolled in the study; peripheral blood mononuclear cells were cultured with or without the human collagen II peptide p261-273 and were examined by immunoscope analysis for the usage of the previously identified shared TCR-beta chains. We report that the presence of T cells carrying rearrangement TRBV25 associated with HLA-DR haplotype and disease activity. HLA-DRB1* haplotypes 04-04, 04-01 and 04-11 were significantly associated with usage of TRBV25, higher disease activity at the onset of disease and poor response to DMARDs. Finally, the HLA-DRB1* haplotype appeared complementary with current serologic tools to predict good and poor responders in a treat to target strategy. The data reported here offer clues to predict the course of the disease and to foresee personalized treatments in RA patients.
Lingua originaleEnglish
pagine (da-a)2037-2045
Numero di pagine9
RivistaEBioMedicine
Volume2
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • ACPA
  • ACPA, anti-cyclic citrullinated peptide antibodies
  • APCs, antigen presenting cells
  • CDR3, complementarity-determining region 3
  • CRP, C-reactive protein
  • Clonotypes
  • Coll261-273, human collagen derived peptide
  • DAS, disease activity score
  • Disease activity
  • ERA, early rheumatoid arthritis
  • ESR, erythrocyte sedimentation rate
  • GWAS, genome wide association studies
  • HAQ, Health Assessment Questionnaire
  • HLA, histocompatibility leucocyte antigen
  • HLA-DRB1
  • MHC, major histocompatibility complex
  • PBMC, peripheral blood mononuclear cells
  • RF, rheumatoid factor
  • RT-PCR, reverse transcription polymerase chain reaction
  • SJC, swollen joint count
  • SNP, single nucleotide polymorphism
  • TCR, T cell receptor
  • TJC, tender joint count
  • TRBJ, junctional beta chain gene of TCR
  • TRBV 25
  • TRBV, variable beta chain gene of TCR

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