Methods for diagnosis and monitoring of toxic epidermal necrolysis

In the present invention, inventors investigate the representation of T cell subsets in Toxic epidermal necrolysis (TEN) a life-threatening cutaneous adverse drug reaction (cADR), characterized by massive epidermal necrosis. To better understand why skin symptoms are so severe in TEN disease, inventors conducted a prospective immunophenotyping study on skin samples and blood from 18 TEN patients, using mass cytometry and next generation TCR sequencing. Deep sequencing of the T cell receptor CDR3 repertoire revealed massive expansion of unique CDR3 clonotypes in blister cells. Over-represented clonotypes were mainly effector memory CD8+CD45RA-CCR7- T cells, and expressed high levels of cytotoxic (Granulysin and Granzymes A & B) and activation (CD38) markers. Thus present invention relates to non-invasive, specific and rapid methods for diagnostic and monitoring Toxic Epidermal Necrolysis. More specifically present invention relates to methods for diagnosis and/or monitoring of Toxic Epidermal Necrolysis through detection of a specific population of T ymphocytes in a subject. The present invention also relates to a method of preventing or treating a Toxic Epidermal Necrolysis in a subject in need thereof.

Keywords: Toxic epiderm necrolysis (TEN), cutaneous adverse drug reaction (cADR), T cell subsets
Patent Application number: EP20 306 460.5 on 27/11/2020
PCT/EP2021/083093 on 26/11/2021
Publications:
Sci Adv 2021 Mar 19 Villani et al Massive clonal expansion of polycytotoxic skin and blood CD8 + T cells in patients with toxic epidermal necrolysis doi: 10.1126/sciadv.abe0013. Print 2021 Mar.

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