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Master Thesis

Prédiction de réponse aux biomédicaments dans les spondyloarthrites, selon les sous-populations lymphocytaires initialese

Abstract : Introduction: the current management of spondyloarthritis (SpA) increasingly requires biologics, which are inefficient in 30 to 40% of patients. Lymphocyte subsets (LS) in SpA have been poorly studied for prognostic, although some of these are clearly implicated in these pathologies. The objective of this study was to determine if LS, before the initiation of biologic therapy could be associated with clinical response to identify potential predictive biomarkers that could be used routinely. Methods: sixty-eight patients with SpA treated with a biologic were included, as well as 150 control subjects free from chronic inflammatory disease. The clinical features commonly assessed during the management of SpA (BASDAI, ASDAS) were recorded at baseline and then at 3 and 6 monthly. The clinical response was defined as (1) maintenance of treatment; (2) 50% reduction of BASDAI or by 2 points and (3) decrease of ASDAS by 1.1 points. Several LS (naive, memory, regulatory T and B cells, Th17 and NK cells) were studied at baseline by flow cytometry. Mann-Whitney U, Chi2 tests and Spearman correlations were used. Results: fifty-three patients had ankylosing spondylitis (AS) and 15 had psoriatic arthritis (PsA). Significantly different frequencies of certain LS were found between SpA and healthy subjects, including B cells (p <0.0001) and memory CD8 (p <0.0001), consistent with their involvement in pathology. The IL-6 receptor (IL-6R) expression was stronger on these LS, confirming a potential role of this cytokine in SpA. No clinical feature was associated with biologic response. In contrast, an association with a lower frequency of NK cells (p = 0.016) was observed in the whole group. This was even more pronounced when an IL-17 inhibitor was used (p = 0.005), but no longer significant with a TNF inhibitor. Frequencies of other LS were also different depending on the type of biologic (trends for the expression of KIR3DL2 on Th17, balance of naive versus memory CD8 cells, expression of IL-6R on B cells). Conlusion: this work confirmed the deregulation of certain LS in SpA. We also established an association between several LS and the clinical response when an IL-17 inhibitor was used, but not for a TNF inhibitor
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Thibault Rabin. Thèse d'exerc...
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Thibault Rabin. Prédiction de réponse aux biomédicaments dans les spondyloarthrites, selon les sous-populations lymphocytaires initialese. Rhumatologie et système ostéo-articulaire. 2018. ⟨dumas-02080008⟩



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