C-type lectin domain family 12, member A: A common denominator in Behçet’s syndrome and acute gouty arthritis

Oguz, Ali Kemal; Yılmaz, Salih; Akar, Nejat; Özdağ, Hilal; Gürler, Aysel; Ateş, Aşkın; Oygür, Çağdaş Şahap; Kılıçoğlu, Sibel Serin; Demırtaş, Selda

doi:10.1016/j.mehy.2015.04.032

Cited by 8 publications

(12 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CLEC12A followed a similar trend with underexpression in the VB subset when compared to both the MB and OB subsets. Recently, this finding was communicated as a preliminary result to support a hypothesis about the role CLEC12A plays in BS [ 49 ]. Taken together, these findings indicate that, in patients with severe forms of BS, negative regulators of inflammation are underexpressed compared to controls and/or patients with milder presentations of the syndrome.…”

Section: Discussionmentioning

confidence: 66%

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 66%

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…[30][31][32] Oguz et al, after noticing the decreased expression of CLEC12A in Turkish BS cases during preliminary analysis of their transcriptome data and by collecting the findings in the literature on CLEC12A , proposed the hypothesis that CLEC12A may be a common denominator in the development of BS and gout. 33 In support of their hypothesis, Oguz et al pointed to the findings of (1) negative correlation ofCLEC12A expression with hyperinflammatory responses, (2) the presence of CLEC12A polymorphisms with functional and clinical effects in certain inflammatory diseases, (3) the dual use of colchicine for the treatment of BS and gout, (4) the exaggerated inflammatory response to uric acid crystals detected in both BS and gout cases, (5) the presence of the genomic locus of the CLEC12A gene (i.e., 12p12-13), among the findings of the GWAS and GWLS of BS, and ( 6) their preliminary finding of decreased CLEC12A expression in Turkish BS cases. 33 At the end of their hypothesis article, Oguz et al stated that, if their hypothesis about CLEC12A is proved with well-designed studies in the future, scientists may be able to go a long way towards the elucidation of the pathogenesis of BS & gout, and also an animal model development for BS.…”

Section: Discussionmentioning

confidence: 99%

“…33 In support of their hypothesis, Oguz et al pointed to the findings of (1) negative correlation ofCLEC12A expression with hyperinflammatory responses, (2) the presence of CLEC12A polymorphisms with functional and clinical effects in certain inflammatory diseases, (3) the dual use of colchicine for the treatment of BS and gout, (4) the exaggerated inflammatory response to uric acid crystals detected in both BS and gout cases, (5) the presence of the genomic locus of the CLEC12A gene (i.e., 12p12-13), among the findings of the GWAS and GWLS of BS, and ( 6) their preliminary finding of decreased CLEC12A expression in Turkish BS cases. 33 At the end of their hypothesis article, Oguz et al stated that, if their hypothesis about CLEC12A is proved with well-designed studies in the future, scientists may be able to go a long way towards the elucidation of the pathogenesis of BS & gout, and also an animal model development for BS. 33 In a more recent review, French researcher Elise Chiffoleau emphasized that, C-type lectin-like receptors, including CLEC12A , could be potential treatment targets by playing important roles in the regulation of sterile inflammation.…”

Section: Discussionmentioning

confidence: 99%

Behçet syndrome: The disturbed balance between anti- (CLEC12A, CLC) and pro-inflammatory (IFI27) gene expressions

Oguz¹,

Oygür²,

Tasır³

et al. 2023

Preprint

View full text Add to dashboard Cite

Behçet syndrome (BS) is a chronic, multisystemic inflammatory condition with unanswered questions regarding its pathogenesis and rational therapeutics. A microarray-based comparative transcriptomic 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 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 expression profiling on peripheral blood samples of the patients and the control subjects. Following 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 was performed using 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

show abstract

“…Downregulation/deficiency of C-type lectin domain family 12, member A (CLEC12A), a C-type lectin-like pattern recognition receptor, is associated with hyperinflammatory responses. Patients with severe forms of Behçet's disease underexpress CLEC12A with respect to patients with mild forms of the disease [15]. Mannose-binding lectin gene-2 polymorphisms and serum mannose-binding lectin levels are associated with the production of high levels of MBL in Behçet's disease.…”

Section: Discussionmentioning

confidence: 99%

The Correlation of CD206, CD209, and Disease Severity in Behçet’s Disease with Arthritis

Choi

Suh

Kim

et al. 2017

Mediators of Inflammation

View full text Add to dashboard Cite

The purpose of this study was to clarify the role of pattern recognition receptors in Behçet's disease (BD). The frequencies of several pattern recognition receptors (CD11b, CD11c, CD32, CD206, CD209, and dectin-1) were analyzed in patients with BD by flow cytometry, and cytokine levels, interleukin- (IL-) 18, IL-23, and IL-17A, were compared in plasma. The analysis was performed in active (n = 13) and inactive (n = 13) stages of BD patients. Rheumatoid arthritis patients (n = 19), as a disease control, and healthy control (HC) (n = 19) were enrolled. The frequencies of CD11b+ and CD32+ cells were significantly increased in active BD patients compared to HC. Disease severity score was correlated to CD11c+, CD206+, and CD209+ in whole leukocytes and CD11b+, CD11c+, CD206+, CD209+, and Dectin-1+ in granulocytes. The plasma levels of IL-17A were significantly different between HC and active BD. IL-18 showed significant difference between active and inactive BD patients. From this study, we concluded the expressions of several pattern recognition receptors were correlated to the joint symptoms of BD.

show abstract

C-type lectin domain family 12, member A: A common denominator in Behçet’s syndrome and acute gouty arthritis

Cited by 8 publications

References 47 publications

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

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

Behçet syndrome: The disturbed balance between anti- (CLEC12A, CLC) and pro-inflammatory (IFI27) gene expressions

The Correlation of CD206, CD209, and Disease Severity in Behçet’s Disease with Arthritis

Contact Info

Product

Resources

About