Behet's: A Disease or a Syndrome? Answer from an Expression Profiling Study

abstract: ...Behets 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 Behets 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 Behets 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.

... disease associated pathways. Based on these clear discrepancies, the designation as Behets 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

... TRAPPC13 , SREK1IP1 , CD180 , CENPK VB vs C 5q15 b ELL2 , TTC37 , ERAP1 MB vs C, VB vs C 5q23 c HBEGF VB vs C 6q16 c MANEA , UFL1 MB vs C, VB vs C 6q25-26 c TULP4 , SYTL3 Significant locus c , d , OB vs C 6q25.1 d PPIL4 VB vs C 7p21 c ARL4A , UMAD1 MB vs C, VB vs C 10q24 c - - 12p12-13 c CD69 , CCND2 , PTPRO , SLC2A3 Significant locus c , d , MB vs C, OB vs C, VB vs C 12p12.1 d BCAT1 , ETNK1 OB vs C, VB vs C 12p13.2-p12.3 b CLEC12A , CLEC12B , KLRC4 MB vs C, OB vs C, VB vs C 12q13 c RPAP3 , ATF1

... Symbol Function b BD Subset(s) c Remarks d Negative regulators of inflammation CD69 (-) regulation of inflammation, leukocyte activation marker VB (), MB () Locus: 12p12-13, CLEC CLEC12A (-) regulator of granulocyte and monocyte function MB () Locus: 12p13.2, CLEC CLEC12B Inhibitory receptor of myeloid cells OB () Locus: 12p13.2, CLEC TNFAIP3 Potent inhibitor of NF-B signaling pathway VB (), OB () Loss-of-function mutations resemble BD Neutrophil granule proteins AZU1 Antimicrobial, chemotactic

... loci of the DEGs were specifically taken into consideration, 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 ) were found to be differentially expressed in BS patients with respect to controls (Tables 3

... special consideration. CD69 , CLEC12A , CLEC12B , and TNFAIP3 are among the well-documented inhibitors of inflammation/immune response [ 44 48 ]. Recently, Zhou et al reported a novel autoinflammatory disorder (haploinsufficiency of A20 [HA20]) occurring as a result of loss-of-function mutations in the TNFAIP3 gene [ 48 ]. It is remarkable to note that, phenotypically, HA20 closely resembles BS with the occurrence of recurrent oral ulcers, dermal abscesses, positive pathergy response, and retinal

infinome is an experiment to study aging. Link your 23andMe account for personalized reports.

Gene: CLEC12B - C-type lectin domain family 12, member B - (NCBI)

Images from Open Access Papers

Association Studies

Search Results from Open Access Papers