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In Rheumatoid Arthritis, Synovitis at Different Inflammatory Sites Is Dominated by Shared but Patient-Specific T Cell Clones.
Musters, Anne; Klarenbeek, Paul L; Doorenspleet, Marieke E; Balzaretti, Giulia; Esveldt, Rebecca E E; van Schaik, Barbera D C; Jongejan, Aldo; Tas, Sander W; van Kampen, Antoine H C; Baas, Frank; de Vries, Niek.
Afiliação
  • Musters A; Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Klarenbeek PL; Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Doorenspleet ME; Laboratory of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Balzaretti G; Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Esveldt REE; Laboratory of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • van Schaik BDC; Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Jongejan A; Laboratory of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Tas SW; Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • van Kampen AHC; Laboratory of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
  • Baas F; Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; and.
  • de Vries N; Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; and.
J Immunol ; 201(2): 417-422, 2018 07 15.
Article em En | MEDLINE | ID: mdl-29891556
ABSTRACT
Genetic and immunological evidence clearly points to a role for T cells in the pathogenesis of rheumatoid arthritis (RA). Selective targeting of such disease-associated T cell clones might be highly effective while having few side effects. However, such selective targeting may only be feasible if the same T cell clones dominate the immune response at different sites of inflammation. We leveraged high-throughput technology to quantitatively assess whether different T cell clones dominate the inflammatory infiltrate at various sites of inflammation in this prototypic autoimmune disease. In 13 RA patients, we performed quantitative next-generation sequencing-based human TCRß repertoire analysis in simultaneously obtained samples from inflamed synovial tissue (ST) from distinct locations within one joint, from multiple joints, and from synovial fluid (SF) and peripheral blood (PB). Identical TCRß clones dominate inflammatory responses in ST samples taken from different locations within a single joint and when sampled in different joints. Although overall ST-SF overlap was comparable to higher ST-ST values, the overlap in dominant TCRß clones in ST-SF comparisons was much lower than ST-ST and comparable to the low ST-PB overlap. In individual RA patients, a limited number of TCRß clones dominate the immune response in the inflamed ST regardless of the location within a joint and which joint undergoes biopsy; in contrast, there is limited overlap of ST with SF or PB TCR repertoires. This limited breadth of the T cell response in ST of the individual RA patient indicates that development of immunotherapies that selectively modulate dominant T cell responses might be feasible.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Sinovite / Linfócitos T / Células Clonais / Inflamação Limite: Female / Humans / Male / Middle aged Idioma: En Revista: J Immunol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Sinovite / Linfócitos T / Células Clonais / Inflamação Limite: Female / Humans / Male / Middle aged Idioma: En Revista: J Immunol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Holanda