In Rheumatoid Arthritis, Synovitis at Different Inflammatory Sites Is Dominated by Shared but Patient-Specific T Cell Clones.
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.
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