We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Discovery of T Cell Receptor β Motifs Specific to HLA-B27-Positive Ankylosing Spondylitis by Deep Repertoire Sequence Analysis.
- Authors
Faham, Malek; Carlton, Victoria; Moorhead, Martin; Zheng, Jianbiao; Klinger, Mark; Pepin, Francois; Asbury, Thomas; Vignali, Marissa; Emerson, Ryan O.; Robins, Harlan S.; Ireland, James; Baechler‐Gillespie, Emily; Inman, Robert D.
- Abstract
Objective Ankylosing spondylitis (AS), a chronic inflammatory disorder, has a notable association with HLA-B27. One hypothesis suggests that a common antigen that binds to HLA-B27 is important for AS disease pathogenesis. This study was undertaken to determine sequences and motifs that are shared among HLA-B27-positive AS patients, using T cell repertoire next-generation sequencing. Methods To identify motifs enriched among B27-positive AS patients, we performed T cell receptor β (TCRβ) repertoire sequencing on samples from 191 B27-positive AS patients, 43 B27-negative AS patients, and 227 controls, and we obtained >77 million TCRβ clonotype sequences. First, we assessed whether any of 50 previously published sequences were enriched in B27-positive AS patients. We then used training and test cohorts to identify discovered motifs that were enriched in B27-positive AS patients versus controls. Results Six previously published and 11 discovered motifs were enriched in the B27-positive AS samples as compared to controls. After combining motifs related by sequence, we identified a total of 15 independent motifs. Both the full set of 15 motifs and a set of 6 published motifs were enriched in the B27-positive AS patients as compared to B27-positive healthy individuals ( P = 0.049 and P = 0.001, respectively). Using an independent cohort, we validated that at least some of these motifs were associated with AS, and not simply with B27-positive status. Conclusion We identified TCRβ motifs that are enriched in B27-positive AS patients as compared to B27-positive healthy controls. This suggests that a common antigen, presented by HLA-B27 and detected by CD8+ T cells, may be associated with AS disease pathogenesis.
- Subjects
ANKYLOSING spondylitis; COMPARATIVE studies; EXPERIMENTAL design; PROBABILITY theory; T cells; HLA-B27 antigen; SEQUENCE analysis
- Publication
Arthritis & Rheumatology, 2017, Vol 69, Issue 4, p774
- ISSN
2326-5191
- Publication type
Article
- DOI
10.1002/art.40028