Exploring the X-linked determinant implicated in the female susceptibility to rheumatic diseases

Concept

The incidence of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is markedly increased in women. Both sex hormones and X chromosomes might contribute to this sex bias. The dosage of X-linked genes is equilibrated between men and women due to the inactivation of one X chromosome (XCI) in female cells. However, XCI is incomplete, leading to increased expression of some X-linked genes.

Facts and figures

Project lead
JC Guéry
University of Toulouse
jean-charles.guery@inserm.fr
FOREUM research grant: €600.000
2020–2023

Meet the team

JC Guéry
University of Toulouse
C Chizzolini
University of Geneva
L Frasca
Istituto Superiore di Sanità

Objectives

It will be investigated whether higher levels of TLR7 expression, arising from the escape of X-chromosome inactivation (XCI) are linked to increased risk of developing autoimmunity specifically in women. This will be achieved by exploring the relevance of TLR7 XCl escape to the pathophysiology of SLE and SSc by assessing the functions of key human immune cell subsets implicated in disease development, in relationship to the dose of TLR7 (one copy or two copies) expressed in each cell subset.

Patient voice

Representative of the Swiss SLE (Lupus-Suisse.ch) and SSc (sclerodermie.ch) patient organizations have reviewed the present proposal and have provided a feedback. It is foreseen that the results will be discussed annually with these representative and upon completion, the study results will be presented at meetings of interested patients’ organizations.