Targeted depletion of TRBV9⁺ T cells as immunotherapy in a patient with ankylosing spondylitis

BRITANOVA, Olga V, Kseniia R LUPYR, Dmitry B STAROVEROV, Irina A SHAGINA, Alexey A ALEKSANDROV, Yakov Y USTYUGOV, Dmitry V SOMOV, Alesia KLIMENKO, Nadejda A SHOSTAK, Ivan V ZVYAGIN, Alexey V STEPANOV, Ekaterina M MERZLYAK, Alexey Nikolayevich DAVYDOV, Mark IZRAELSON, Evgeniy S EGOROV, Ekaterina A BOGDANOVA, Anna K VLADIMIROVA, Pavel A IAKOVLEV, Denis A FEDORENKO, Roman A IVANOV, Veronika I SKVORTSOVA, Sergey LUKYANOV and Dmitriy CHUDAKOV. Targeted depletion of TRBV9⁺ T cells as immunotherapy in a patient with ankylosing spondylitis. NATURE MEDICINE. BERLIN: NATURE PORTFOLIO, 2023, vol. 2023, No 29, p. 2731-2736, 18 pp. ISSN 1078-8956. Available from: https://dx.doi.org/10.1038/s41591-023-02613-z.

Basic information

• Original name: Targeted depletion of TRBV9⁺ T cells as immunotherapy in a patient with ankylosing spondylitis
• Authors: BRITANOVA, Olga V, Kseniia R LUPYR, Dmitry B STAROVEROV, Irina A SHAGINA, Alexey A ALEKSANDROV, Yakov Y USTYUGOV, Dmitry V SOMOV, Alesia KLIMENKO, Nadejda A SHOSTAK, Ivan V ZVYAGIN, Alexey V STEPANOV, Ekaterina M MERZLYAK, Alexey Nikolayevich DAVYDOV, Mark IZRAELSON, Evgeniy S EGOROV, Ekaterina A BOGDANOVA, Anna K VLADIMIROVA, Pavel A IAKOVLEV, Denis A FEDORENKO, Roman A IVANOV, Veronika I SKVORTSOVA, Sergey LUKYANOV and Dmitriy CHUDAKOV.
• Edition: NATURE MEDICINE, BERLIN, NATURE PORTFOLIO, 2023, 1078-8956.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10608 Biochemistry and molecular biology
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 82.900 in 2022
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1038/s41591-023-02613-z
• UT WoS: 001087110800001
• Keywords in English: ARTHRITIS; ankylosing spondylitis; psoriatic arthritis; T cell receptors (TCRs); cognate antigenic epitopes; TRBV9-containing CD8(+) TCR motif
• Tags: International impact, Reviewed

Abstract

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.