Résumé :
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Communication n° 507 Myasthenia Gravis (MG) is associated with thymic hyperplasia characterized by germinal center formation in the thymus. The glucocorticoids, widely used in the MG treatment, induce remodeling and cell distribution modifications within the thymus, decreasing especially the number of germinal centers. To understand the glucocorticoid effects, we analyzed the thymic transcriptome of MG patients treated or untreated by corticotherapy. We compared thymuses from baby girls (control) to thymuses from age-matched adult females from healthy donors, MG patients untreated or treated by glucocorticoids. RNAs were hybridized onto the human cDNA arrays from Agilent. The raw data obtained with the GenePix software were corrected by intra and inter normalizations and statistically analyzed. Using the SAM program, we identified 396 genes dysregulated in untreated patients compared to healthy adults and 423 genes in treated compared to untreated patients. Among these genes, only 21 genes dysregulated in MG are normalized by glucocorticoids indicating that corticotherapy acts on many genes not implicated in MG. Indeed, by applying clustering analysis on the 13,572 genes spotted onto the slide, 26% of the genes are not dysregulated in MG but are dysregulated by glucocorticoids. Moreover 23% of the genes are dysregulated in MG and even more in treated patients. This non-specific action of glucocorticoids reflects their side-effects in MG and underlines the necessity to identify specific therapeutic targets. Thus, using a Mann-Whitney's test, we carried on a gene by gene analysis for the 168 up-regulated genes identified by SAM in MG patients : 34 genes are significantly down-regulated by glucocorticoids with 18 implicated in the immune response, and especially related to B cells. Among them, the chemokine CXCL13 which is known to be involved in the formation and maintain of germinal centers could play an important role in MG pathophysiology.
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