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Master Thesis

Étude de l’association entre les différentes atteintes cliniques et l’expression d’OX40 sur les lymphocytes T auxiliaires dans le lupus érythémateux systémique

Abstract : OX40+ Tph (CXCR5-, ICOS+, PD-1hi): a novel biomarker of disease activity and renal involvement in lupus? Introduction. Systemic lupus erythematosus is an autoimmune disease that is heterogeneous in presentation and complex in pathophysiology. The OX40/OX40L co-stimulation axis has been described as potentially implicated in pathogenesis by participating in a loop of amplification of autoantibody production through T follicular helpers (CXCR5+, ICOS+, PD-1+) - stimulated B cells. Recently a new subpopulation of T helpers, the T peripheral helpers (Tph) (CXCR5-, ICOS+, PD-1hi), has been described. However, their role in the physiopathology of SLE and how OX40/OX40L axis is involded in their function, is still unknown. Objective. To study the expression of OX40 by the different sub-populations of helper T lymphocytes and to look for an association between OX40 expression on these T cells and a particular clinical profile of the disease. Methods. Blood samples from 61 SLE patients followed in Bordeaux University hospital and 38 controls were studied. The fraction of each subtype of T cells (LTh1, LTh2, LTh17, LTfh and LTph) as well as the percentage of each subtype expressing OX40 were determined by flow cytometry. These data were cross-referenced with clinical data using STATA© 13.1 software. Results. The expression of OX40 by each T cell helper subtype was greater in SLE patients compared to the control subjects. However, only the percentage of OX40+ Tph was correlated with disease activity markers namely the SLEDAI (positive correlation between OX40+Tph% and SEDAI; r=0.33; p=0.008), anti-dsDNA antibody levels (r=0.38; p=0.003), C3 (negative correlation between OX40+Tph% and C3; r=-0.49; p= 0.0002) and C4 levels (r=-0.41; p= 0.017). Activated ICOS+ Tph correlated with activity markers but not ICOS+ Tfh. Finally, the percentage of OX40+ Tph was associated with active renal impairment (mean ± SD of percentage of circulating OX40+ Tph in patients with nephritis 33.1% ± 17.1 % vs 20.8% ± 15.1 in patients without nephritis; p=0.007) and positively correlated with proteinuria (r=0.31; p=0.017). Conclusion. SLE patients have an increased percentage of OX40+ Tph compared to healthy subjects and this number is associated with clinical and biological activity markers as well as renal impairment.
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Itsaso Odriozola. Étude de l’association entre les différentes atteintes cliniques et l’expression d’OX40 sur les lymphocytes T auxiliaires dans le lupus érythémateux systémique. Sciences du Vivant [q-bio]. 2020. ⟨dumas-02945282⟩



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