A study of the repertoire of activated T-cell clones obtained from a patient with ankylosing spondylitis

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Pirogov Russian National Research Medical University, Moscow, Russia

Correspondence should be addressed: Ivan V. Zvyagin
ul. Ostrovityanova, d. 1, Moscow, Russia, 117997; moc.liamg@nigayvzi

About paper

Funding: this work was supported by the Ministry of Education and Science of the Russian Federation, Project ID RFMEFI60716X0158.

Acknowledgements: we are grateful to the patient who has kindly given his consent to participate in the study; to Denis Fedorenko, a hematologist and Professor of Maximov Hematology and Cell Therapy Department (Pirogov National Medical Surgical Center) for his consultations; Elena Kovalenko, a senior researcher at Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, for her assistance in conducting a flow cytometry analysis.

Received: 2017-12-15 Accepted: 2017-12-25 Published online: 2018-02-16

Recent studies of T-cell clonal repertoires of patients with ankylosing spondylitis (AS) have led to the discovery of AS-associated T-cell clones with a highly homologous T-cell receptor structure. The role of T-lymphocytes in the disease progression cannot be elucidated without analyzing the diversity and abundance of functionally different T-cell clones found in patients with AS. Using a state-of-the-art technique for T-cell repertoire profiling based on massively parallel sequencing, we, for the first time, studied the T-cell receptor repertoire of activated T-cells from the peripheral blood of a patient with AS. We have demonstrated that a subpopulation of CD38+HLA-DR+ T-lymphocytes is highly diverse both in terms of clonal diversity and abundance of the identified clonotypes, suggesting diverse antigen specificity of the activated peripheral blood T-cells. Most of the activated T-cell clonotypes had low abundance in total population of peripheral blood T-cells. In the repertoire of activated T-cells we have found the clonotype TRBV9_CASSVGVYSTDTQYF_TRBJ2-3, previously discovered in AS and reactive arthritis, and a few other clonotypes of cytotoxic and helper T-cells that may have a role in promoting inflammation in AS patients. Presence of the AS-associated clonotype in activated T-cell subset suggests that the T-cells might play an active role in ongoing inflammation during the disease progression. This provides rationale for further research of their antigen specificity and role in triggering or maintaining AS.

Keywords: T-cell repertoire, ankylosing spondylitis, activated T-lymphocytes, Bekhterev's disease, T-cell subpopulation, clonal repertoire