Publication details

Targeted depletion of TRBV9<sup>+</sup> 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 Nikolayevich 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 Dmitriy
Year of publication	2023
Type	Article in Periodical
Magazine / Source	NATURE MEDICINE
MU Faculty or unit	Central European Institute of Technology
Citation
Web	https://www.nature.com/articles/s41591-023-02613-z
Doi	http://dx.doi.org/10.1038/s41591-023-02613-z
Keywords	ARTHRITIS; ankylosing spondylitis; psoriatic arthritis; T cell receptors (TCRs); cognate antigenic epitopes; TRBV9-containing CD8(+) TCR motif
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-B27-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-B27-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.