Novel association of the CD226 (DNAM-1) Gly307Ser polymorphism in Wegener's granulomatosis and confirmation for multiple sclerosis in German patients

Wieczorek, Stefan; Hoffjan, Sabine; Chan, Andrew; Rey, Linda K.; Harper, Lorraine; Fricke, Harald; Holle, Julia; Gross, Wolfgang L.; Epplen, Jörg T.; Lamprecht, Peter

doi:10.1038/gene.2009.44

Cited by 76 publications

(40 citation statements)

References 35 publications

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“…Although the role of CD155-DNAM-1 interactions in solid organ transplantation is not known, recent genome-wide association studies have shown that a singlenucleotide polymorphism in DNAM-1 is associated with the development of type 1 diabetes, rheumatoid arthritis, and Wegener's granulomatosis. 30,31 The effect of this polymorphism on DNAM-1 expression or function was not experimentally addressed, but sequence analysis suggests that the susceptibility allele could reduce DNAM-1 expression. 30 Indeed, Lofgren et al 32 recently identified a 3-variant haplotype in DNAM-1 that reduces its expression in lymphocytes and that confers increased susceptibility to systemic lupus erythematosus.…”

Section: Discussionmentioning

confidence: 99%

CD155 on Human Vascular Endothelial Cells Attenuates the Acquisition of Effector Functions in CD8 T Cells

Escalante

Rossum

Lee

et al. 2011

ATVB

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Objective-CD155 is a cell surface protein that has recently been described to exert immune regulatory functions. We have characterized the expression of CD155 on human vascular endothelial cells (ECs) and examined its role in the regulation of T-cell activation. Methods and Results-CD155 was expressed on resting human vascular ECs and was upregulated in an interferon-␥ (IFN␥)-dependent manner. When the function of CD155 in regulating T-cell activation was examined, antibodymediated neutralization of CD155 did not affect CD8 T-cell proliferation in response to stimulation with ECs. However, neutralization of CD155 activity or small interfering RNA-mediated inhibition of CD155 expression in ECs increased expression of IFN␥ and cytotoxic effector function in activated CD8 T cells. Key Words: cytokines Ⅲ endothelium Ⅲ immune system Ⅲ CD155 Ⅲ T cell H uman vascular endothelial cells (ECs) act as semiprofessional antigen-presenting cells and, in this way, regulate immune responses by presenting antigenic peptides and cell surface proteins to T cells in peripheral tissues. 1,2 This immunoregulatory property of the endothelium is established in the control T-cell responses in solid organ transplantation and may regulate immune responses in autoimmunity and some cardiovascular diseases. 1 With regard to the expression of cell surface proteins, human ECs provide positive costimulatory signals to T cells mainly through leukocyte functional antigen-3, intercellular adhesion molecule-1, CD154, 41BB ligand, inducible co-stimulator ligand, and OX40 ligand. 3 These signals are required for the activation of memory CD4 and CD8 T cells by ECs. In contrast, ECs also express cell surface proteins, such as PD-L1, that inhibit T cell responses. 4,5 The expression of immune regulatory proteins on ECs is controlled by cytokines. In particular, interferon-␥ (IFN␥) is especially pertinent to EC immunobiology as it induces the expression of both immune activating and inhibitory proteins. 6,7 The precise effects of IFN␥ on determining the phenotype of ECs may depend on its cooperative signaling with other cytokines or the temporal regulation of target genes. Overall, understanding the role of immune regulatory proteins on the surface of ECs is important for providing insight into the regulation of immune responses. Conclusion-CD155Activation of CD8 T cells by allogeneic human ECs induces proliferation, IFN␥ secretion, and the expression of cytotoxic effector proteins, such as granzyme B. 8 These properties of activated CD8 T cells play a pathological role in allograft rejection. 9 Also, IFN␥ production from activated T cells within arteries drives pathological smooth muscle cell proliferation in the arterial intima and vasomotor dysfunction, thereby contributing to the pathogenesis of some vascular diseases. 10 Interleukin (IL)-10 is also produced by effector T cells that secrete IFN␥, as well as by some induced regulatory T cells. Expression of IL-10 in effector T cells develops late after T-cell activation, correlates with increased i...

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Section: Discussionmentioning

confidence: 99%

CD155 on Human Vascular Endothelial Cells Attenuates the Acquisition of Effector Functions in CD8 T Cells

Escalante

Rossum

Lee

et al. 2011

ATVB

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“…39 A weaker association was found between MPO-AAV and HLA-DQ. Polymorphisms in the genes IL-10, CTLA-4, CD226, ITGB2, PTPN22, IL2RA, and PRTN3, [40][41][42] previously reported to play a role in AAV, were included. 39 However, none of these had an odds ratio that was significant genome-wide (P value ,5310 2 8 In the North American genome-wide studies, a link between SEMA6A and GPA was found, 38 but this was not confirmed in an independent cohort of European patients.…”

Section: Genetic Featuresmentioning

confidence: 99%

Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA Vasculitis

Hilhorst

Paassen

Tervaert

2015

Journal of the American Society of Nephrology

171

137

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In patients with GN or vasculitis, ANCAs are directed against proteinase 3 (PR3) or myeloperoxidase (MPO). The differences between PR3-ANCA-associated vasculitis (AAV) and MPO-AAV described in the past have been supplemented during the last decade. In this review, we discuss the differences between these two small-vessel vasculitides, focusing especially on possible etiologic and pathophysiologic differences. PR3-AAV is more common in northern parts of the world, whereas MPO-AAV is more common in southern regions of Europe, Asia, and the Pacific, with the exception of New Zealand and Australia. A genetic contribution has been extensively studied, and there is a high prevalence of the HLA-DPB1*04:01 allele in patients with PR3-AAV as opposed to patients with MPO-AAV and/or healthy controls. Histologically, MPO-AAV and PR3-AAV are similar but show qualitative differences when analyzed carefully. Clinically, both serotypes are difficult to distinguish, but quantitative differences are present. More organs are affected in PR3-AAV, whereas renal limited vasculitis occurs more often in patients with MPO-AAV. For future clinical trials, we advocate classifying patients by ANCA serotype as opposed to the traditional disease type classification.

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“…In Chinese Han population, rs763361 was also associated with systemic lupus erythematosus (SLE) 15 . Rs763361 was also found to be associated with MS in Western and Asian countries 12,13,16 . However, no studies have investigated the role of rs763361 in the pathogenesis NMo and MS in Chinese Han population.…”

Section: Original Articlementioning

confidence: 99%

CD226 Gly307Ser Association With Neuromyelitis Optica in Southern Han Chinese

Liu

Wang

Liu

et al. 2012

Can. J. Neurol. Sci.

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Background:Neuromyelitis optica (NMO) and multiple sclerosis (MS) are autoimmune diseases of the central nervous system with complex pathogeneses. NMO was once considered to be a severe variant of MS. There has been more evidence that a non-synonymous exchange (rs763361/Gly307Ser) in the gene for CD226 is linked to several autoimmune diseases including multiple sclerosis (MS). However, no studies have investigated the role of rs763361 in the pathogenesis of NMO.Objectives:The goal of our study is to evaluate the role of CD226 Gly307Ser in neuromyelitis optica (NMO) in Southern Han Chinese.Methods:Eight-nine NMO patients, 93 relapsing-remitting multiple sclerosis (RRMS) patients, and 122 controls (CTLs) were enrolled. The rs763361 alleles of the subjects were determined by sequencing-based typing.Results:The results strongly support that the TT genotypes are associated with NMO but are not significantly correlated with susceptibility for MS.Conclusions:CD226 Gly307Ser may correlate with risk of NMO in Southern Han Chinese.

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Novel association of the CD226 (DNAM-1) Gly307Ser polymorphism in Wegener's granulomatosis and confirmation for multiple sclerosis in German patients

Cited by 76 publications

References 35 publications

CD155 on Human Vascular Endothelial Cells Attenuates the Acquisition of Effector Functions in CD8 T Cells

CD155 on Human Vascular Endothelial Cells Attenuates the Acquisition of Effector Functions in CD8 T Cells

Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA Vasculitis

CD226 Gly307Ser Association With Neuromyelitis Optica in Southern Han Chinese

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