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Blood genomic expression profile for Behçet’s disease.

ABSTRACT: Behçet’s disease (BD) is a multisystemic immuno-inflammatory disorder characterized by a generalized vasculitis, particularly at the orogenital mucosa and eye. It is a complex disease with unclear pathogenesis. To better understand BD´s etiology, we performed genomic expression profiling of patients and controls.

ORGANISM(S): Homo sapiens

PROVIDER: GSE17114 | GEO | 2011/07/01

SECONDARY ACCESSION(S): PRJNA119733

REPOSITORIES: GEO

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Blood genomic expression profile for Behçet’s disease.

Project description:Behçet’s disease (BD) is a multisystemic immuno-inflammatory disorder characterized by a generalized vasculitis, particularly at the orogenital mucosa and eye. It is a complex disease with unclear pathogenesis. To better understand BD´s etiology, we performed genomic expression profiling of patients and controls. Gene expression profiling was performed in peripheral blood mononuclear cells (PBMCs) of 15 patients and 14 sex- and age-matched controls using Affymetrix microarrays. The ages of the patients and controls do not match on a one-to-one basis, but they match very well on average. The average age at examination of cases and controls is 37y.

2011-07-01 | E-GEOD-17114 | biostudies-arrayexpress

transcriptional profiling of neutrophils in Behcet's Disease (BD).

Project description:Behçet’s Disease (BD) is a chronic and systemic vasculitis with unknown etiology. Although BD is considered a condition linking both autoimmunity and autoinflammation, aberrant innate immunity has emerged in its significant pathogenetic role, among which neutrophils directly drive inflammation in BD. To investigate neutrophil aberrance in BD, we performed bulk RNA-sequencing on isolated peripheral neutrophils from 10 pairs of BD and sex- and age-matched healthy control (HCs).

2022-11-01 | GSE205867 | GEO

mRNA expression profiling of PBMCs from Behcet’s disease

Project description:Behçet’s disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. However, a comprehensive understanding of the immune disturbances in BD and how they contribute to BD pathogenesis is lacking. Here, we performed single-cell and bulk RNA sequencing to profile peripheral blood mononuclear cells (PBMCs) and isolated monocytes from BD patients and healthy controls. This dataset is the bulk RNA sequencing part (next generation sequencing-based genome-wide transcriptional profiling), which contains the transcriptional profilings of freshly isolated PBMCs from19 samples (10 healthy controls and 9 BD patients).

2022-03-18 | GSE198533 | GEO

Single-cell transcriptomics highlights the proinflammatory contribution of C1q-high monocytes to Behçet’s disease

Project description:Behçet’s disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. Here, we performed single-cell sequencing to profile peripheral blood mononuclear cells (PBMCs) and isolated monocytes from BD patients and healthy donors. We observed prominent expansion and transcriptional changes in monocytes in PBMCs from BD patients. Deciphering the monocyte heterogeneity revealed the accumulation of C1q-high (C1qhi) monocytes in BD. Pseudotime inference indicated that BD monocytes markedly shifted their differentiation toward inflammation-accompanied and C1qhi monocyte-ended trajectory. Further experiments showed that C1qhi monocytes enhanced phagocytosis and proinflammatory cytokine secretion, and multi-platform analyses revealed the significant clinical relevance of this subtype. Mechanistically, C1qhi monocytes were induced by activated IFN-γ signaling in BD patients, and were decreased by tofacitinib treatment. Our study illustrates BD immune landscape and the unrecognized contribution of C1qhi monocytes to BD hyperinflammation, showing their potential as therapeutic targets and clinical assessment indexes.

2022-03-15 | GSE198616 | GEO

DNA microarray analysis of PBMCs from Behçet’s disease (BD) patients

Project description:To examine if gene expression profiles of many Behçet’s disease (BD) patients are commonly abnormal compared to those of healthy volunteers, we performed a genome-wide complementary DNA microarray analysis using an Agilent Hu44K array; RNA samples were isolated from the PBMCs of 41 individual BD patients (32 females and 9 males) and 17 normal volunteers.

2016-01-21 | GSE70403 | GEO

Distinct transcriptional profile of blood mononuclear cells in Behcet’s disease: insights into the central role of neutrophil chemotaxis

Project description:Both innate and adaptive immune responses are reportedly increased in Behcet’s disease (BD), a chronic-relapsing systemic vasculitis lying at the intersection between autoinflammation and autoimmunity. To further study pathophysiologic molecular mechanisms operating in BD we searched for transcriptome-wide changes in blood mononuclear cells from these patients. We performed 3’ mRNA next generation sequencing-based genome-wide transcriptional profiling followed by analysis of differential expression signatures, KEGG pathways, GO biological processes and transcription factor signatures al 25 samples (11 healthy controls and 14 BD).

2021-05-25 | GSE165254 | GEO

The Behçet’s Disease associated Hap10 variant of ERAP1 generates a low affinity HLA-B*51 peptidome through differential processing of two subpeptidomes

Project description:HLA-B*51, the main risk factor for Behçet’s disease (BD), binds two main subpeptidomes consisting of low affinity peptides with Ala as their second amino acid and higher affinity peptides with Pro at this position. A low activity variant of ERAP1, Hap10, is uniquely associated with BD susceptibility in epistasis with HLA-B*51. The peptidome presented by HLA-B*51:08 in a cell line expressing Hap10 was compared with the HLA-B*51:01 peptidome from a cell line expressing higher activity variants of ERAP1. The differences due to ERAP1 could be clearly distinguished from those due to subtype polymorphism. The latter should not affect disease susceptibility, since both HLA-B*51 subtypes are associated with BD. In the lower activity, BD-associated, ERAP1 context longer peptides were generated, the Pro2 subpeptidome was significantly reduced, and the Ala2 subpeptidome was correspondingly increased and showed a higher frequency of ERAP1-susceptible P1 residues. These effects are readily explained by the low activity of the disease-associated Hap10 variant, and together resulted in a significantly altered HLA-B*51 peptidome of lower affinity. The differences between both B*51 subtypes affected residue usage at various internal positions of the peptide ligands, including P3, where B*51:01 showed preference for aromatic residues whereas B*51:08 preferred smaller and polar ones. The profound effects of the BD-associated Hap10 haplotype on the nature and affinity of HLA-B*51/peptide complexes could significantly alter T-cell and NK cell recognition, providing a basis for the joint association of ERAP1 and HLA-B*51 to BD.

2018-10-24 | PXD006215 | Pride

Blood transcriptome indicates different disease etiology in pediatric ANCA-associated vasculitis subtypes.

Project description:Blood transcriptome indicates different disease etiology in pediatric ANCA-associated vasculitis subtypes.

| PRJNA532630 | ENA

Reduction of Neutrophil Activation by Phosphodiesterase 4 Blockade in Behçet's Disease

Project description:Objective: Behçet's disease (BD) is a systemic vasculitis with inflammatory lesions mediated by cytotoxic T cells and neutrophils. Apremilast, an orally available small-molecule that selectively inhibits phosphodiesterase 4 (PDE4), has been recently approved for the treatment of BD. We aimed to investigate the effect of PDE4 inhibition on neutrophil activation in BD. Methods: We studied surface markers and reactive oxygen species (ROS) by flow cytometry, neutrophils extra cellular traps (NETs) and molecular signature of neutrophils by transcriptomic before and after PDE4 inhibition. Results: Activation surface markers (CD64, CD66b, CD11b and CD11c), ROS production and NETosis were up-regulated in BD as compared to Healthy Donors (HD) neutrophils. Transcriptome analysis showed 1021 significantly dysregulated neutrophils genes between BD and HD. Among dysregulated genes, we highlighted a great enrichment for pathways linked to innate immunity, intracellular signaling and chemotaxis in BD. Skin lesions of BD showed increased infiltration of neutrophils that co-localized with PDE4. Inhibition of PDE4 by apremilast strongly inhibited neutrophil surface activation markers as well as ROS production, NETosis, and genes and pathways related to innate immunity, intracellular signaling and chemotaxis. Conclusion: We pointed out key biological effects of apremilast on neutrophils in BD.

2023-04-01 | GSE225904 | GEO

Transcriptome analysis of Myotonic Dystrophy type 2 (DM2) patients.

Project description:Myotonic Dystrophy Type-2 (DM2) is an autosomal dominant disease caused by the expansion of a CCTG tetraplet repeat. It is a multisystemic disorder, affecting skeletal muscles, the heart, the eye, the central nervous system and the endocrine system. Whole mRNAs expression was measured in the muscle of DM2 patients and compared it to controls.We identified distinct genes modulated in DM2 patients compared to controls.

2015-04-05 | GSE37084 | GEO

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