| Title: |
Targeted depletion of TRBV9+ T cells as immunotherapy in a patient with ankylosing spondylitis |
| Authors: |
Britanova, Olga V.; Lupyr, Kseniia R.; Staroverov, Dmitry B.; Shagina, Irina A.; Aleksandrov, Alexey A.; Ustyugov, Yakov Y.; Somov, Dmitry V.; Klimenko, Alesia; Shostak, Nadejda A.; Zvyagin, Ivan V.; Stepanov, Alexey V.; Merzlyak, Ekaterina M.; Davydov, Alexey N.; Izraelson, Mark; Egorov, Evgeniy S.; Bogdanova, Ekaterina A.; Vladimirova, Anna K.; Iakovlev, Pavel A.; Fedorenko, Denis A.; Ivanov, Roman A.; Skvortsova, Veronika I.; Lukyanov, Sergey; Chudakov, Dmitry M. |
| Source: |
Nature Medicine ; volume 29, issue 11, page 2731-2736 ; ISSN 1078-8956 1546-170X |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2023 |
| Description: |
Autoimmunity is intrinsically driven by memory T and B cell clones inappropriately targeted at self-antigens. Selective depletion or suppression of self-reactive T cells remains a holy grail of autoimmune therapy, but disease-associated T cell receptors (TCRs) and cognate antigenic epitopes remained elusive. A TRBV9-containing CD8 + TCR motif was recently associated with the pathogenesis of ankylosing spondylitis, psoriatic arthritis and acute anterior uveitis, and cognate HLA-B*27-presented epitopes were identified. Following successful testing in nonhuman primate models, here we report human TRBV9 + T cell elimination in ankylosing spondylitis. The patient achieved remission within 3 months and ceased anti-TNF therapy after 5 years of continuous use. Complete remission has now persisted for 4 years, with three doses of anti-TRBV9 administered per year. We also observed a profound improvement in spinal mobility metrics and the Bath Ankylosing Spondylitis Metrology Index (BASMI). This represents a possibly curative therapy of an autoimmune disease via selective depletion of a TRBV-defined group of T cells. The anti-TRBV9 therapy could potentially be applicable to other HLA-B*27-associated spondyloarthropathies. Such targeted elimination of the underlying cause of the disease without systemic immunosuppression could offer a new generation of safe and efficient therapies for autoimmunity. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41591-023-02613-z |
| Availability: |
https://doi.org/10.1038/s41591-023-02613-z; https://www.nature.com/articles/s41591-023-02613-z.pdf; https://www.nature.com/articles/s41591-023-02613-z |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.2F7DF70B |
| Database: |
BASE |