Project description:Behçet syndrome (BS) is a chronic, multisystemic inflammatory condition with unanswered questions regarding its pathogenesis, classification, and rational therapeutics. A microarray-based comparative genome-wide expression analysis was performed to elucidate the molecular mechanisms of BS and identify any potential therapeutic targets. Twenty-nine BS patients (B) and 15 age and sex-matched control subjects (C) were recruited. Patients with BS were grouped as mucocutaneous (M), ocular (O), and vascular (V) according to their clinical phenotypes. GeneChip Human Genome U133 Plus 2.0 arrays were used for gene expression profiling on peripheral blood samples of the patients and the control subjects. Following the documentation of the differentially expressed gene (DEG) sets, the data were further evaluated with bioinformatics analysis/visualization and enrichment tools. Validation of the microarray data were performed using real-time qRT-PCR. When p<0.05 and fold change >2.0 were chosen, the following numbers of DEGs were obtained; B vs. C: 28, M vs. C: 20, O vs. C: 8, V vs. C: 555, M vs. O: 6, M vs. V: 324, O vs. V: 142. Venn diagram analysis indicated only two genes, CLEC12A and IFI27, in the intersection of M vs. C ∩ O vs. C ∩ V vs. C. Another noteworthy gene appeared as CLC in the DEG sets. Cluster analyses successfully clustered distinct clinical phenotypes of BS. While innate immunity-related biological processes were enriched in the M group, adaptive immunity-specific biological processes were significantly enriched in the O and V groups. Distinct clinical phenotypes of BS patients displayed distinct expression profiles. In Turkish patients with BS, expression differences regarding the genes CLEC12A, IFI27, and CLC seemed to be operative in BS pathogenesis. Based on these findings, future research should consider the immunogenetic heterogeneity of BS clinical phenotypes. Two anti-inflammatory genes, namely CLEC12A and CLC, may be valuable as therapeutic targets and may also help design an experimental model in BS.
Project description:Multicellular spheroid from 10 Ehlers-Danlos SYndrome (EDS) patients were used to perform transcritomic experiment. These were compared to 4 control healty samples with the aim to identify dysregulated genes and pathways and to use this information to propose potential drugs that could be repurposed for the treatment, based on computational approaches to drug repositioning.In summary, this comprehensive study expands our understanding of the molecular basis of Ehlers-Danlos syndrome, particularly relating to COL3A1 mutations. The integration of transcriptomic analysis, pathway studies, and drug repurposing strategies provides a robust framework for identifying potential therapeutic strategies for EDS.
Project description:Biallelic mutations in SLC29A3 cause histiocytosis-lymphadenopathy plus syndrome, also known as H syndrome (HS). HS is a complex disorder, with ~25% of patients developing autoinflammatory complications consisting of unexplained fevers, persistently elevated inflammatory markers and unusual lymphadenopathies, with infiltrating CD68+, S100+ and CD1a– histiocytes, resembling the immunophenotype found in Rosai-Dorfman disease (RDD). We investigated the transcriptomic profiles of monocytes, non-activated (M0), classically-activated (M1) and alternatively-activated macrophages (M2) in two patients with HS, one without autoinflammatory (HS1) and one with autoinflammatory complications (HS2). RNA sequencing revealed a dysregulated transcriptomic profile in both HS patients compared to healthy controls (HC). HS2, when compared to HS1, had several differentially expressed genes, including genes associated with lymphocytic-histiocytic predominance (e.g. NINL) and immunodeficiencies (e.g. B2M). The transcriptomic and cytokine profiles of HS patients were comparable to patients with SAID with high levels of TNF. SERPINA1 gene expression was found to be upregulated in all patients. Moreover, higher levels of IFNg were found in the serum of both HS patients when compared to HC. Gene-ontology (GO) enrichment analysis of the DEGs in HS patients revealed the terms "type I IFN", "IFNg signalling pathway" and "immune responses" as the top 3 most significant terms for monocytes. Finally, the transcriptomic profiles of M0 and M1 macrophages, from patient HS2, were similar to the transcriptomic profile of tissue biopsies taken from patients with RDD-like lymphadenopathies. Monocytes and macrophages from both HS patients showed transcriptomic profiles similar to SAIDs and with a unique dysregulated IFNgsignalling. These findings may help to find better therapeutic options for this rare disorder.
Project description:This SuperSeries is composed of the following subset Series: GSE12997: Comparative transcriptomic analysis of BA- or BL- associated murine colonic epithelium GSE12998: Comparative transcriptomic analysis of BA- or BL- associated murine colonic epithelium after O157 infection Refer to individual Series