CD226 (DNAM-1) is associated with susceptibility to juvenile idiopathic arthritis

Reinards, T H C M; Albers, H M; Brinkman, Dmc; Kamphuis, Sylvia; Rossum, Marion A J van; Girschick, Hermann; Wouters, Carine; Hoppenreijs, Esther P A H; Saurenmann, Rotraud K.; Hinks, Anne; Ellis, Justine A.; Bakker, Egbert; Verduijn, Willem; Slagboom, P. Eline; Huizinga, T.W.J.; Toes, René E. M.; Houwing-Duistermaat, Jeanine J.; Cate, Rebecca ten; Schilham, Marco W.

doi:10.1136/annrheumdis-2013-205138

Cited by 33 publications

(21 citation statements)

References 60 publications

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“…21 A genetic association study was also performed in patients from Northwest European descent and confirmed the association of several genes (PTPN22, VTCN1, the IL2-IL21 region, ANKRD55 and TNFA) with JIA. 19 We confirmed the JIA-U susceptibility locus in rs11074967, which is located near the PRM1 gene. PRM1 is a member of protamines which have been isolated from spermatozoa, playing a role in sperm chromatin condensation.…”

Section: Discussionsupporting

confidence: 68%

“…The r 2 value for linkage disequilibrium had to be less than 0.8 between adjacent loci and the minor allele frequency had to be larger than 0.05 in the CHB. Based on the above criteria, we finally included 84 SNPs in or near 60 loci: ANTXR2, 18 CXCR4, 18 CD226, 19 TNFA, 19 MIF, 19 CD28, 19 KIAA1109, 19 PSMC6, 20 PSMA3, 20 STAT4, 21 24 IL20, 24 CDGAP/ARHGAP31, 25 C3orf1/ TIMMDC1, 25 IL15, 25 NRBF2-EGR2, 25 JMJD1C, 25 REEP3, 25 IGF1R-FAM169B, 25 CHD9-TOX3, 25 IRF5, 26 BLK, 27 C5orf30, 27 CD247, 27 ORMDL3, 27 PTPRC, 27 ERAP1, 28 LPP, 29 TRAF1/C5, 30 IL2RA, 31 Intergenic, 31 32 The selected SNPs were genotyped by MassARRAY platform (Sequenom, San Diego, California, USA) and iPLEX Gold Genotyping Assay, and analysed by TYPER software V.4.0. The PCR was performed with the GeneAmp PCR System 9700 thermocycler (ABI, Foster City, California, USA).…”

Section: Single Nucleotide Polymorphism Choicementioning

confidence: 99%

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Genetic aspects of idiopathic paediatric uveitis and juvenile idiopathic arthritis associated uveitis in Chinese Han

Deng

Tan

et al. 2019

Br J Ophthalmol

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BackgroundIdiopathic paediatric uveitis (IPU) and juvenile idiopathic arthritis associated uveitis (JIA-U) are the two most common entities in paediatric uveitis. This study addressed the possible association of IPU and JIA-U with genes that had been shown earlier to be associated with juvenile idiopathic arthritis.MethodsWe carried out a case-control association study involving 286 IPU, 134 JIA-U patients and 743 healthy individuals. A total of 84 candidate single nucleotide polymorphisms (SNPs) in 60 genes were selected for this study. The MassARRAY platform and iPLEX Gold Genotyping Assay was used to genotype 83 candidate SNPs and the remaining SNP (rs27293) was analysed using the TaqMan SNP Genotyping Assay.ResultsNo evidence was found for an association of the candidate polymorphisms tested with IPU. Six SNPs (PRM1/rs11074967, JAZF1/rs73300638, IRF5/rs2004640, MEFV/rs224217, PSMA3/rs2348071 and PTPN2/rs7234029) showed an association with JIA-U (p<1.0×10−2).ConclusionOur findings showed associations of six SNPs (PRM1/rs11074967, JAZF1/rs73300638, IRF5/rs2004640, MEFV/rs224217, PSMA3/rs2348071 and PTPN2/rs7234029) with JIA-U. No association was detected between the 84 tested SNPs and IPU.

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Section: Discussionsupporting

confidence: 68%

Section: Single Nucleotide Polymorphism Choicementioning

confidence: 99%

Genetic aspects of idiopathic paediatric uveitis and juvenile idiopathic arthritis associated uveitis in Chinese Han

Deng

Tan

et al. 2019

Br J Ophthalmol

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“…It is expressed on T and NK cells and is involved in co-stimulation of these cells. This association was not seen on a follow-up Immunochip study but the association was confirmed in a meta-analysis [59]. Other polymorphisms associated with JIA are located in the IL2-IL21 region, the AFF3 gene and ANKRD55 [45,59,60].…”

Section: Genetics Of Oligoarticular Jia/polyarticular Rf-negative Jiamentioning

confidence: 99%

“…In a 2014 study Reinards et al performed a genetic association study which identified a polymorphism in the CD226 ( DNAM1 ) gene in association with JIA [59]. DNAX accessory molecule-1 is a type 1 membrane protein belonging to the Ig-supergene family.…”

Section: Genetics Of Oligoarticular Jia/polyarticular Rf-negative Jiamentioning

confidence: 99%

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Hersh

Prahalad

2015

Journal of Autoimmunity

118

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Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthropathy of childhood. Juvenile idiopathic arthritis is believed to be a complex genetic trait influenced by both genetic and environmental factors. Twin and family studies suggest a substantial role for genetic factors in the predisposition to JIA. Describing the genetics is complicated by the heterogeneity of JIA; the International League of Associations for Rheumatology (ILAR) has defined seven categories of JIA based on distinct clinical and laboratory features. Utilizing a variety of techniques including candidate gene studies, the use of genotyping arrays such as Immunochip, and genome wide association studies (GWAS), both human leukocyte antigen (HLA) and non-HLA susceptibility loci associated with JIA have been described. Several of these polymorphisms (e.g. HLA class II, PTPN22, STAT4) are shared with other common autoimmune conditions; other novel polymorphisms that have been identified may be unique to JIA. Associations with oligoarticular and RF-negative polyarticular JIA are the best characterized. A strong association between HLA DRB1:11:03/04 and DRB1:08:01, and a protective effect of DRB1:15:01 have been described. HLA DPB1:02:01 has also been associated with oligoarticular and RF-negative polyarticular JIA. Besides PTPN22, STAT4 and PTPN2 variants, IL2, IL2RA, IL2RB, as well as IL6 and IL6R loci also harbor variants associated with oligoarticular and RF-negative polyarticular JIA. RF-positive polyarticular JIA is associated with many of the shared epitope encoding HLA DRB1 alleles, as well as PTPN22, STAT4 and TNFAIP3 variants. ERA is associated with HLA B27. Most other associations between JIA categories and HLA or non-HLA variants need confirmation. The formation of International Consortia to ascertain and analyze large cohorts of JIA categories, validation of reported findings in independent cohorts, and functional studies will enhance our understanding of the genetic underpinnings of JIA.

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“…TIGIT competes with the costimulatory molecule CD226 for binding to the poliovirus receptor (PVR)/Nectin-like-5/CD155 prominently expressed on APCs (17). CD226 has been identified as an autoimmune susceptibility gene, with a SNP (Gly307Ser; rs763361) linked to type 1 diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) Wegners granulomatosis, celiac disease (CD), and juvenile idiopathic arthritis (JIA)(18, 19). This recently described axis shares many parallel functions with the CD28:CTLA-4 pathway in terms of promoting or inhibiting T cell activation, respectively (20–22).…”

Section: Introductionmentioning

confidence: 99%

Divergent Phenotypes of Human Regulatory T Cells Expressing the Receptors TIGIT and CD226

Fuhrman

Yeh

Seay

et al. 2015

The Journal of Immunology

222

182

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Regulatory T cells (Treg) play a central role in counteracting inflammation and autoimmunity. A more complete understanding of cellular heterogeneity and the potential for lineage plasticity in human Treg subsets may identify markers of disease pathogenesis and facilitate the development of optimized cellular therapeutics. To better elucidate human Treg subsets, we conducted direct transcriptional profiling of CD4+FOXP3+Helios+ thymic-derived Treg (tTreg) and CD4+FOXP3+Helios− T cells, followed by comparison to CD4+FOXP3−Helios− T conventional (Tconv) cells. These analyses revealed that the coinhibitory receptor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) was highly expressed on tTreg. TIGIT and the costimulatory factor CD226 bind the common ligand CD155. Thus, we analyzed the cellular distribution and suppressive activity of isolated subsets of CD4+CD25+CD127lo/− T cells expressing CD226 and/or TIGIT. We observed TIGIT is highly expressed and upregulated on Treg following activation and in vitro expansion and is associated with lineage stability and suppressive capacity. Conversely, the CD226+TIGIT− population was associated with reduced Treg purity and suppressive capacity following expansion, along with a marked increase in IL-10 and effector cytokine production. These studies provide additional markers to delineate functionally distinct Treg subsets that may help direct cellular therapies and provide important phenotypic markers for assessing the role of Treg in health and disease.

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CD226 (DNAM-1) is associated with susceptibility to juvenile idiopathic arthritis

Abstract: The CD226 gene has been identified as novel association with JIA, and a SNP near CD28 as a suggestive association. Both genes are probable candidate risk factors, since they are involved in costimulation of T cells.

Cited by 33 publications

References 60 publications

Genetic aspects of idiopathic paediatric uveitis and juvenile idiopathic arthritis associated uveitis in Chinese Han

Genetic aspects of idiopathic paediatric uveitis and juvenile idiopathic arthritis associated uveitis in Chinese Han

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Divergent Phenotypes of Human Regulatory T Cells Expressing the Receptors TIGIT and CD226

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