title: Behçet's: A Disease or a Syndrome? Answer from an Expression Profiling Study.
abstract: Behçet's disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet's is "a disease or a syndrome". To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection "MB vs C" ∩ "OB vs C" ∩ "VB vs C". Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as "Behçet's syndrome" (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis.
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey.|Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Ali Kemal
authors.initials: AK
authors.lastname: Oğuz
authors.affiliation: Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Seda Taşır
authors.initials: ST
authors.lastname: Yılmaz
authors.affiliation: Department of Internal Medicine, Başkent University School of Medicine, Ankara, Turkey.
authors.forename: Çağdaş Şahap
authors.initials: ÇŞ
authors.lastname: Oygür
authors.affiliation: Department of Biochemistry, Ufuk University School of Medicine, Ankara, Turkey.
authors.forename: Tuba
authors.initials: T
authors.lastname: Çandar
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey.
authors.forename: Irmak
authors.initials: I
authors.lastname: Sayın
authors.affiliation: Department of Histology and Embryology, Ufuk University School of Medicine, Ankara, Turkey.
authors.forename: Sibel Serin
authors.initials: SS
authors.lastname: Kılıçoğlu
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey.
authors.forename: İhsan
authors.initials: İ
authors.lastname: Ergün
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Ankara University School of Medicine, Ankara, Turkey.
authors.forename: Aşkın
authors.initials: A
authors.lastname: Ateş
authors.affiliation: Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Hilal
authors.initials: H
authors.lastname: Özdağ
authors.affiliation: Department of Pediatrics, TOBB University of Economics and Technology Hospital, Ankara, Turkey.
authors.forename: Nejat
authors.initials: N
authors.lastname: Akar
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000175:diagnosis / Q000235:genetics*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D066264:Datasets as Topic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008040:Genetic Linkage; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D015203:Reproducibility of Results; D059467:Transcriptome; D055815:Young Adult