title: Collagen Specific T-Cell Repertoire and HLA-DR Alleles: Biomarkers of Active Refractory Rheumatoid Arthritis.
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.
authors: Institute of General Pathology, Catholic University of the Sacred Heart, Rome, Italy; Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.
authors: Gabriele
authors: G
authors: Di Sante
authors: Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.
authors: Barbara
authors: B
authors: Tolusso
authors: Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.
authors: Anna Laura
authors: AL
authors: Fedele
authors: Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.
authors: Elisa
authors: E
authors: Gremese
authors: Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.
authors: Stefano
authors: S
authors: Alivernini
authors: Institute of General Pathology, Catholic University of the Sacred Heart, Rome, Italy.
authors: Chiara
authors: C
authors: Nicolò
authors: Institute of General Pathology, Catholic University of the Sacred Heart, Rome, Italy.
authors: Francesco
authors: F
authors: Ria
authors: Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.
authors: Gianfranco
authors: G
authors: Ferraccioli
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D015415:Biomarkers; D003094:Collagen / Q000737:chemistry / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000276:immunology; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D003094:Collagen
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