Clinical and genetic associations of T-cell receptors repertoire in psoriasis

Abstract

Background. An urgent task for modern researchers is to identify and analyze the mechanisms of immune-dependent diseases at the molecular level. This contributes to the discovery and development of new therapeutic targets, as well as methods of influencing them. A disease of particular interest in this aspect is psoriasis. Psoriasis is a chronic inflammatory skin disease, in the pathogenesis of which an important role is attributed to T cells. Psoriasis is characterized by inflammatory infiltrates in the skin. A number of studies have found an increased content of some clones of T cells carrying certain T-cell receptors in dermal structures of patients with psoriasis. However, most studies of T-cell receptor repertoires in psoriasis have been performed on small patient samples, and little attention has been paid to the relationship of these repertoires with clinical characteristics of the disease.

Aims: To identify specific sequence combinations encoding the T-cell receptors associated with psoriasis as a potential therapeutic target based on the results of a new generation of massive sequencing analysis of the T-cell receptor repertoire.

Methods. The study used a next-generation sequencing (NGS) method. In our study, we examined the repertoire of T-cell receptors in psoriasis patients in affected and unaffected skin in a sufficient sample (n = 20) and compared the repertoire of T-cell receptors in psoriasis with that in the skin of healthy subjects.

Results. It was shown that psoriasis patients had more unique T-cell receptor sequences in the affected skin compared to unaffected skin, as well as compared to the skin of healthy subjects. A number of T-cell receptor sequences unique to psoriasis patients were found, and a number of moderate strength correlations between the number of these sequences in the affected skin and the Psoriasis Area and Severity Index (PASI) were shown.

Conclusion: These results contribute to a better understanding of the pathogenesis of psoriasis and open opportunities for studying potential therapeutic targets in psoriasis.