Peizeng Yang

Chongqing Medical University, Ch’ung-ch’ing-shih, Chongqing Shi, China

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Publications (152)505.65 Total impact

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    ABSTRACT: Complement is involved in many immune-mediated diseases. However, the association of its copy number variations (CNVs) and polymorphisms with Behcet's disease (BD) and Vogt-Koyanagi-Harada syndrome (VKH) is unknown. We examined copy number and mRNA expression by real-time PCR. Cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) in genotyped individuals was measured by ELISA. The frequencies of having more than two copies of C3 were significantly increased in BD and VKH, whereas CNV of C5 was only associated with BD. Increased frequencies of the GG genotype of C3 rs408290 and C5 rs2269067 were found in BD. No association was observed between C3 and C5 SNPs and VKH. mRNA expression in the high CNV group and GG cases of C3 and C5 was significantly higher compared to other genotypes. Increased interleukin-17 and IFN-γ was observed in the high CNV group and GG genotype cases of C3. Interleukin-17 but not IFN-γ was increased in the high CNV group and GG genotype cases of C5. No effect of C3 or C5 genetic variants was seen on the production of TNF-α, IL-10, IL-1β, MCP-1, IL-6 and IL-8. Our study thus provides further evidence for a role of complement in the pathogenesis of uveitis.
    Scientific Reports 08/2015; 5:12989. DOI:10.1038/srep12989 · 5.58 Impact Factor
  • Peizeng Yang
    Current Molecular Medicine 08/2015; · 3.61 Impact Factor
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    ABSTRACT: Previous studies have identified that disturbed apoptosis was involved in the pathogenesis of Behçet disease (BD) and VKH syndrome. This study aims to investigate whether copy number variations (CNVs) of apoptosis-related genes, including FAS, CASPASE8, CASPASE3 and BCL2, are associated with BD and VKH syndrome in Han Chinese. A two-stage association study was performed in 1014 BD patients, 1051 VKH syndrome patients and 2076 healthy controls. TaqMan(®) Copy Number Assays and real-time PCR were performed. The first-stage study showed that increased frequency of high FAS copy number (>2) was found in BD (P = 1.05×10(-3) ) and VKH syndrome (P = 2.56×10(-3) ). Replication and combined study confirmed the association of high copy number (>2) of FAS with BD (P = 3.35×10(-8) ) and VKH syndrome (P = 9.77×10(-8) ). A significant up-regulated mRNA expression of FAS was observed in anti-CD3/CD28 antibodies-stimulated CD4(+) T cells from individuals carrying a high gene copy number (>2) as compared to normal diploid 2 copy number carriers (P = 0.004). Moreover, the mRNA expression of FAS both in active patients with BD and VKH syndrome was significantly higher than that in controls (P = 0.001 and P = 0.007, respectively). Our findings suggest that a high copy number of FAS gene confers risk for BD and VKH syndrome. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Human Mutation 07/2015; DOI:10.1002/humu.22829 · 5.05 Impact Factor
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    ABSTRACT: Purpose: T cells play an important role in the pathogenesis of uveitis. Recent studies have indicated that the TNFSF15 gene that encodes the TL1A protein can regulate the differentiation and activation of T cells. TNFSF15 gene polymorphisms have been found to be associated with several autoimmune disorders. A possible association of TNFSF15 with acute anterior uveitis (AAU) has not yet been reported and was therefore the purpose of our study. Methods: Eight single nucleotide polymorphisms (SNPs) were examined using TaqMan SNP Genotyping Assay or PCR-restriction fragment length polymorphism in 983 AAU patients and 1128 healthy controls. Genotype distributions and allele frequencies were compared using χ2 analysis between AAU patients and healthy controls. Stratified analysis was also performed according to ankylosing spondylitis (AS) status. The TNFSF15 mRNA expression was quantified by real-time PCR. Results: A significantly decreased frequency of the TT genotype in TNFSF15-rs3810936 was found in AAU patients (P = 6.36 × 10−6, corrected P[Pc] = 1.52 × 10−4, OR = 0.6, 95% CI = 0.5–0.8). Stratification according to AS status did not reveal a difference concerning the association with TNFSF15-rs3810936. None of the other TNFSF15 SNPs tested were associated with AAU. Conclusions: This study shows an association between TNFSF15-rs3810936 and AAU and suggests that the TL1A/DR3 pathway may be implicated in the pathogenesis of this disease.
    Investigative Ophthalmology &amp Visual Science 07/2015; 56(8):4605-4610. DOI:10.1167/iovs.15-16896 · 3.66 Impact Factor
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    ABSTRACT: Polymorphisms in the genes encoding C3 and C5 are associated with several immune-mediated diseases. However, the association of C3 and C5 SNPs with acute anterior uveitis (AAU) has not yet been investigated and was the purpose of the study described. Genotyping was performed for six SNPs in C3 and four SNPs in C5 in 395 AAU patients with ankylosing spondylitis (AS), 397 AAU patients without AS, and 597 healthy controls by PCR-restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP assay. The mRNA expression was detected by real-time PCR. Cytokine production and total C5 serum concentrations were measured by ELISA. The frequency of the GG genotype of rs2269067 in C5 was increased in AAU patients with or without AS compared to controls (Pc = 4.0 × 10-5, odds ratio [OR] = 1.94 and Pc = 9.4 × 10-5, OR = 1.89, respectively). The mRNA and serum concentrations of C5 were significantly increased in rs2269067 GG cases as compared to that in CG or CC cases (P = 0.012, P = 0.002; P = 0.021, P = 0.006, respectively). An increased production of interleukin-17 was observed in rs2269067 GG cases compared to CG or CC cases (P = 5.1 × 10-4, P = 1.4 × 10-4, respectively). The C5 rs2269067 GG genotype confers risk for AAU in a Chinese population and is associated with an elevated C5 serum concentration and an increased IL-17 production.
    Investigative ophthalmology & visual science 07/2015; 56(8):4954-4960. DOI:10.1167/iovs.15-16645 · 3.66 Impact Factor
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    ABSTRACT: To determine the genetic lesions and to modify the clinical diagnosis for a Chinese family with significant intrafamilial phenotypic diversities and unusual presentations. Three affected patients and the asymptomatic father were included and received comprehensive systemic examinations. Whole exome sequencing (WES) was performed for mutation detection. Structural modeling test was applied to analyze the potential structural changes caused by the missense substitution. The proband showed a wide spectrum of systemic anomalies, including bilateral ectopia lentis, atrial septal defect, ventricular septal defect, widening of tibial metaphysis with medial bowing, and dolichostenomelia in digits, while her mother and elder brother only demonstrated similar skeletal changes. A recurrent mutation, PHEX p.R291*, was found in all patients, while a de novo mutation, FBN1 p.C792F, was only detected in the proband. The FBN1 substitution was also predicted to cause significant conformational change in fibrillin-1 protein, thus changing its physical and biological properties. Taken together, we finalized the diagnosis for this family as X-linked hypophosphatemia (XLH), and diagnosed this girl as Marfan syndrome combined with XLH, and congenital heart disease. Our study also emphasizes the importance of WES in assisting the clinical diagnosis for complicated cases when the original diagnoses are challenged.
    Journal of Translational Medicine 06/2015; 13(1). DOI:10.1186/s12967-015-0534-9 · 3.99 Impact Factor
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    ABSTRACT: This study aimed to investigate the role of genetic variants including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of TBX21, GATA3, Rorc and Foxp3 genes in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. Genotyping of 25 SNPs was performed by iPLEX system (Sequenom) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). TaqMan real time PCR was used to assess CNVs. The expression of Rorc and Foxp3 were examined by real-time PCR and cytokine production was measured by ELISA. High Rorc CNV was associated with the susceptibility to BD (P = 8.99 × 10(-8), OR = 3.0), and low Foxp3 CNV predisposed to BD in female patients (P = 1.92 × 10(-5), OR = 3.1). CNVs for the investigated genes were not altered in VKH syndrome. Further functional studies demonstrated that the relative mRNA expression levels of Rorc were increased in individuals with high Rorc copy number, but not for Foxp3. Increased production of IL-1β and IL-6 was found in individuals carrying a high CNV of Rorc. Our study showed that high CNVs of Rorc and low CNVs of Foxp3 confer risk for BD but not for VKH syndrome. The tested 25 SNPs in TBX21, GATA3, Rorc and Foxp3 did not associate with BD and VKH syndrome.
    Scientific Reports 04/2015; 5:9511. DOI:10.1038/srep09511 · 5.58 Impact Factor
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    ABSTRACT: Bach2 was reported to play a key role in T lymphocyte development and maturation to mediate immunological homeostasis. Several autoimmune and immune-related diseases were shown to be associated with Bach2 gene polymorphisms. The current study was designed to explore the association between Bach2 gene polymorphism with Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) in a Chinese Han population. -427 patients with BD, 422 patients with VKH and 623 controls were recruited for the first stage from a Chinese Han population. The second stage included another set of 388 patients with BD and 460 healthy subjects. PCR fragment length polymorphism methodology was used for genotyping. Frequencies of genotypes and alleles were measured by direct counting and compared between cases and controls by χ(2) test. No difference could be detected between patients suffering from BD or VKH with healthy controls concerning allele and genotype frequencies of rs11755527, rs3757247, rs12212193 and rs2474619. Although in the first stage the frequencies of genotype CC and AC of rs2474619 showed a weak statistical difference between BD and the control group (Pc=0.02), the difference was lost after the second stage and combined stage experiment. The investigated Bach2 gene polymorphisms (rs11755527, rs3757247, rs12212193 and rs2474619) are not related to the susceptibility to either VKH or BD in our investigated Chinese Han population. This project was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-CCC-12002184). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    The British journal of ophthalmology 04/2015; DOI:10.1136/bjophthalmol-2014-306163 · 2.81 Impact Factor
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    Liping Du · Hui Peng · Quan Wu · Meidong Zhu · Delun Luo · Xiao Ke · Peizeng Yang · Bo Lei
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    ABSTRACT: Conbercept (KH902), a novel recombinant, soluble vascular endothelial growth factor (VEGF) receptor-IgG fusion protein, has been developed as a new drug for ocular neovascularization and macular edema. The present study aims to clarify the changes in conbercept levels, VEGF, and intraocular pressure (IOP) after the intravitreal injection of conbercept into diabetic mouse eyes. Five-week-old C57BL/6 mice were injected with streptozotocin to induce diabetes. Total VEGF and conbercept levels in the eyes were detected using an ELISA kit at -2 h, 1 h, 1 d, 4 d, 8 d, 16 d, 28 d, and 34 d after intravitreal injection of conbercept into diabetic and control mice. IOP was measured with a noninvasive TonoLab tonometer 7 d after intravitreal conbercept injection. The concentration of conbercept in the treated eyes increased immediately after injection and remained at high levels for 4 d (29.77±27.19 ng/ml, 20.28±28.85 ng/ml, and 42.43±36.51 ng/ml for days 1, 2, and 4, respectively). The concentration of conbercept in the untreated fellow eyes increased from day 2 to day 4 after injection with a level of about 1% of that in the injected eyes. Conbercept concentrations in both the treated and fellow eyes decreased from day 7 after intravitreal injection. The concentration of VEGF in the treated eyes increased significantly 1 h after injection when compared with the baseline measured 2 h before injection in both the diabetic and control mice (645.91±86.47 pg/ml versus 296.10±76.11 pg/ml and 860.50±201.47 pg/ml versus 377.69±70.72 pg/ml, respectively). VEGF concentration reached its peak 24 h after injection and then decreased thereafter. At day 7 after intravitreal injection, the difference in IOP between mice that received conbercept and mice that received PBS injections was not significant (p>0.05). Conbercept and total VEGF levels in the mouse eyes were elevated after intravitreal injection of conbercept. Increased VEGF levels likely reflect VEGF sequestered by conbercept. These data could be helpful in understanding the metabolism of anti-VEGF drugs in the eye and for determining the protocol of multiple intravitreal injections of conbercept in patients.
    Molecular vision 02/2015; 21:185-93. · 2.25 Impact Factor
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    ABSTRACT: Purpose: To test whether gene copy number variations(CNVs) of TLRs are associated with uveitis. Methods: CNVs of the TLRs were detected by Real-time PCR. The first stage study comprised 400 Behcet's disease(BD) patients, 400 VKH syndrome patients, 400 acute anterior uveitis associated with or without ankylosing spondylitis patients and 600 healthy subjects. The second stage included another set of 578 BD patients and 1000 healthy controls. The frequencies of TLR gene copy number types (TLR1,TLR2,TLR3,TLR5,TLR6,TLR7,TLR9, TLR10), were compared between patients and controls using the χ2 test. Real-Time PCR was used to detect mRNA expression from PBMCs obtained from healthy controls following stimulation with the TLR7 agonist R848. Levels of TNF-α, IL-6 and IL-1β in culture supernatants were measured by ELISA. Results: All TLRs tested except TLR7 had a gene copy number of 2 in more than 98% of individuals tested. In the first stage study, we found a significantly increased frequency of >1 copy of TLR7(located on the X chromosome) in male BD patients and >2 copies in female patients(Pc=0.021; Pc=0.048, respectively). A second stage and combined study confirmed the association (PC=1.14×10-6, PC=9.12×10-5, respectively). TLR7 mRNA expression in PBMCs was increased in male healthy carriers having >1 copy of TLR7 or females having >2 copies following stimulation with R848(P=0.021, P=0.006, respectively). No effect of the various TLR7 copies on the release of TNF-α, IL-6 and IL-1β could be detected. Conclusions: This study provides evidence that a high copy number of TLR7 confers risk for BD in a Chinese Han population. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
    Investigative Ophthalmology &amp Visual Science 02/2015; 56(3). DOI:10.1167/iovs.14-15030 · 3.66 Impact Factor
  • Ke Li · Shengping Hou · Jian Qi · Aize Kijlstra · Peizeng Yang
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    ABSTRACT: Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) are two common form of uveitis in China. The aim of this study was to investigate the association of C-type lectin domain family 16, member A (CLEC16A) gene polymorphisms with Vogt-Koyanagi-Harada syndrome and Behcet's disease in a Chinese Han population. A two-stage association study was carried out in 988 VKH syndrome patients,400 BD patients and 976 healthy controls. Eight single nucleotide polymorphisms of CLEC16A gene were determined with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data were analyzed by χ(2) test or Fisher's exact test and corrected for multiple comparisons by the Bonferroni method. The first stage study showed that the frequency of the A allele of rs6498169 was significantly decreased in VKH syndrome patients (Pc = 1.1 × 10(-2), OR = 0.7, 95%CI = 0.6-0.9). No significant association was observed in the other 7 SNPs between VKH syndrome patients and controls. No association was found with BD for the 8 SNPs tested. We further confirmed the association of single nucleotide polymorphism rs6498169 with VKH syndrome in another cohort. Consistent with the first stage study, the combined study showed significantly lower frequencies of the AA genotype and the A allele of rs6498169 in VKH syndrome patients (Pc = 3.5 × 10(-4), OR = 0.6, 95%CI = 0.5-0.7; Pc = 8.2 × 10(-4), OR = 0.8, 95%CI = 0.7-0.9, respectively). In conclusion, the study suggested that a CLEC16A polymorphism may be protective against VKH syndrome in a Chinese Han population. Copyright © 2015. Published by Elsevier Ltd.
    Experimental Eye Research 01/2015; 132. DOI:10.1016/j.exer.2015.01.004 · 3.02 Impact Factor
  • Shengping Hou · Aize Kijlstra · Peizeng Yang
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    ABSTRACT: Uveitis is usually considered as an intraocular inflammation characterized by variety of clinical features. Behcet's disease (BD), Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis (AAU), and birdshot chorioretinopathy (BCR) are examples of noninfectious forms of uveitis. Although the precise pathogenesis remains unclear, accumulating evidence shows that complex genetic backgrounds coupled with an aberrant immune response may be implicated in the development of uveitis. The complement and pattern recognition systems are both important factors of the innate immune system and are involved in the pathogenesis of uveitis. Copy number variants (CNVs) of complement component 4 have been found to be associated with BD and VKH syndrome, but not with AAU. Several CNVs and gene polymorphisms of toll-like receptors were found to be associated with BD. Leukocytes are an important part of the adaptive immune system and various molecules on these cells play an important role in the development of uveitis. Genes encoding for human leukocyte antigens (HLAs) have been shown to be associated with certain uveitis entities, including BD (HLA-B51), VKH syndrome (HLA-DR4, DRB1/DQA1), AAU (HLA-B27), and BCR (HLA-A29). Genome wide association studies showed that the IL-23R locus was a shared risk factor for multiple uveitis entities including BD, AAU, and VKH syndrome. In addition, various other non-HLA genes are also associated with BD or VKH syndrome, such as IL-10, STAT4, STAT3, and UBAC2. These studies support the hypothesis that genetic factors play a key role in the pathogenesis of uveitis. © 2015 Elsevier Inc. All rights reserved.
    Progress in molecular biology and translational science 01/2015; 134:283-98. DOI:10.1016/bs.pmbts.2015.04.009 · 3.11 Impact Factor
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    ABSTRACT: This study aimed to investigate the association of interleukin (IL)-10 gene polymorphisms with Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in the Chinese Han population. A two-stage association study was performed on 718 BD patients, 300 VKH patients, and 1,753 controls. Genotyping of the IL-10 gene was performed for six single nucleotide polymorphisms (SNPs), including rs1800871, rs1800872, rs1800896, rs3021094, rs3790622, and rs1554286 using PCR-restricted fragment length polymorphism or TaqMan SNP assays. Real-time PCR was performed to test the IL-10 mRNA expression of the associated polymorphisms. The first-stage result showed significantly increased frequencies of the rs1800871 T allele, rs1800872 A allele, and rs1554286 T allele in BD patients compared with controls (Pcorrected (Pcorr) = 1.82×10(-5), OR = 1.837; Pcorr = 6.1×10(-5), OR = 1.780; Pcorr = 3.15×10(-5), OR = 1.794, respectively). There was no association of the tested six SNPs with VKH syndrome. A second-stage study was therefore performed in BD patients to validate the result of the first stage, showing a significantly increased frequency of the rs1800871 T allele (Second stage, Pcorr = 5.59×10(-5), OR = 1.493; Combined data, Pcorr = 3.65×10(-11), OR = 1.632). Compared to the controls, an increased frequency of the rs1800871 T allele was observed in BD patients with extraocular findings, including genital ulcers, skin lesions, and a positive pathergy test. No difference was found among the mRNA expressions of IL-10 in the peripheral blood mononuclear cells (PBMCs) of controls with different genotypes of rs1800871 after stimulation of lipopolysaccharide (LPS) or anti-CD3/CD28 antibodies. The findings showed that IL-10 is a risk gene for BD but not for VKH syndrome.
    Molecular vision 01/2015; 21:589-603. · 2.25 Impact Factor
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    ABSTRACT: Purpose: Recent studies have shown that a decrease of regulatory T (Treg) cells may contribute to the activity of acute anterior uveitis (AAU) and ankylosing spondylitis (AS). A number of immunogenetic factors including IL2RA, miR-27a, miR-182 and FoxO1 are associated with Treg cell function. In this study, we investigated the association between polymorphisms of these genes and AAU with or without AS in a Chinese Han population. Methods: Using PCR-RFLP assay, a two-stage association study was performed in 680 AAU patients with or without AS and 1280 controls. Gene expression was quantified by real-time PCR. Results: In the first stage study, an association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 230 AAU patients with AS, 240 AAU patients without AS and 650 controls. The results showed significantly increased frequencies of the FoxO1/rs2297626 AA genotype and A allele in AAU patients with AS (AA genotype: P =6.23×10-5, OR=1.86; A allele: P =2.17×10-4, OR=1.53). No significant association of the other 9 SNPs with AAU with or without AS was observed. In the second stage study, an association analysis of FoxO1/rs2297626 was performed in 210 AAU patients with AS and 630 controls. The second stage and combined studies confirmed the association of FoxO1/rs2297626 with AAU with AS (AA genotype: P =3.45×10-8, OR=1.85; A allele: P =1.55×10-7, OR=1.55). Conclusions:This study suggests that FoxO1, but not miR-27a, miR-182 and IL2RA, contributes to the genetic susceptibility of AAU with AS, but none of the tested polymorphisms confer risk to AAU without AS.
    Investigative Ophthalmology &amp Visual Science 11/2014; 55(12):7970-7974. DOI:10.1167/iovs.14-15460 · 3.66 Impact Factor
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    ABSTRACT: To investigate the associations of IL17A, IL17F, IL23A, and IL23R copy number variants (CNVs) with Vogt-Koyanagi-Harada (VKH) syndrome and Behçet's disease (BD) and the possible mechanisms involved. Two-stage case-control and functional studies. A total of 1159 VKH patients, 1036 BD patients, and 2050 controls were enrolled. TaqMan real-time polymerase chain reaction assay was used for genotyping of copy number variant. Cell proliferation was measured by colorimetric assay. Association of CNVs in IL17A, IL17F, IL23A, and IL23R with BD and VKH syndrome and the functional roles of IL17F CNVs. Increased frequencies of more than 2 copies of IL17F and IL23A were found in BD patients as compared with controls (IL17F: P = 4.17 × 10(-8); odds ratio [OR], 2.2; IL23A: P = 2.86 × 10(-11); OR, 2.8, respectively). A similar result was found for VKH syndrome (IL17F: P = 2.84 × 10(-13); OR, 2.7; IL23A: P = 4.46 × 10(-17); OR, 3.4, respectively). Interestingly, the association of IL17F and IL23A with BD was found only in male patients (IL17F: P = 1.06 × 10(-6); OR, 2.3; IL23A, P = 3.81 × 10(-8); OR, 2.8, respectively), but not in female patients. No association of CNVs in IL17A and IL23R was found for BD and VKH syndrome. IL17F protein levels were correlated positively with gene copy numbers (P = 3.43 × 10(-7)). Individuals with high IL17F copies showed enhanced peripheral blood mononuclear cells (PBMC) proliferation (P = 5.67 × 10(-3)). High gene copy numbers of IL17F and IL23A were associated with BD and VKH syndrome. Enhanced IL17F protein production and PBMC proliferation were associated with high IL17F copy numbers. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
    Ophthalmology 11/2014; 122(3). DOI:10.1016/j.ophtha.2014.09.025 · 6.17 Impact Factor
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    ABSTRACT: Interleukin-37 (IL-37) is emerging as an important inhibitor of immune response. This study was set up to investigate the expression of IL-37 in Vogt-Koyanagi-Harada (VKH) disease and to explore its possible regulatory role during inflammation. Twenty-four untreated active VKH patients, 10 VKH patients receiving corticosteroids and cyclosporin A (CsA), and 35 healthy controls were included in this study. IL-37 expression in lipopolysaccharides (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) from these 3 groups was assayed by real-time polymerase chain reaction (RT-PCR) and flow cytometry. Cytokines in the supernatants of stimulated PBMCs and CD4(+) T cells were assayed by enzyme-linked immunosorbent assay (ELISA). Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation were measured by flow cytometry. VKH patients showed a decreased IL-37 and IL-27 expression and increased IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels in PBMC culture supernatants. IL-37 significantly inhibited the production of IL-1β, IL-6, and TNF-α, but induced IL-27 expression. VKH patients treated with corticosteroids combined with CsA showed a regression of the intraocular inflammation, and treatment was associated with an enhanced IL-37 production. IL-37 did not affect the production of IL-17, interferon-gamma (IFN-γ), or IL-10 from CD4(+) T cells. The present study suggests that a decreased IL-37 expression in VKH patients is associated with a reduced control of the inflammatory response. Treatment of VKH patients with corticosteroids and CsA is associated with an increased expression of IL-37, which suggests that corticosteroids and CsA may partly exert their immunosuppressive effect by upregulating IL-37 production.
    Journal of Interferon & Cytokine Research 10/2014; 35(4). DOI:10.1089/jir.2014.0042 · 3.90 Impact Factor
  • Shengping Hou · Jian Qi · Dan Liao · Jing Fang · Lu Chen · Aize Kijlstra · Peizeng Yang
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    ABSTRACT: Aims Considering the phenotypical consequences and association of C4 copy number variation (CNV) with various autoimmune diseases, we aimed to examine C4 CNVs for 1027 patients with Vogt-Koyanagi-Harada (VKH) syndrome and 2083 controls. Methods C4 CNVs were examined by real-time PCR for 1027 patients with VKH and 2083 controls. Peripheral blood mononuclear cells (PBMC) were prepared from venous blood by Ficoll-Hypaque density-gradient centrifugation for cell culture. Cytokine production was examined by ELISA. Results The expression of total C4 in serum was significantly decreased in patients with VKH as compared with controls (p=0.0010). A significant positive association between C4 expression with C4 CNVs was found (p=0.0023, r2=0.92). CNV analysis identified significantly decreased frequencies of more than two copies of C4A or more than four copies of total C4 in patients with VKH (Pc=1.42×10−3 to 3.56×10−4, OR=0.67 to 0.70). Linkage analysis showed the independent association of C4 with VKH syndrome from human leucocyte antigen (HLA)-DR4. No significant association was observed concerning type 1 T helper cell (Th1) cytokines and Th17 cytokine production by stimulated PBMCs and C4A copy number. Conclusions Our findings indicate a decreased expression of serum C4 and a decreased frequency of high C4 gene copy number in patients with VKH. Trial registration number Chinese Clinical Trial Registration Number: ChiCTR-CCC-12002184.
    British Journal of Ophthalmology 09/2014; 98(12). DOI:10.1136/bjophthalmol-2014-305596 · 2.81 Impact Factor
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    ABSTRACT: To identify new genetic risk factors for Vogt-Koyanagi-Harada (VKH) syndrome, we conducted a genome-wide association study of 2,208,258 SNPs in 774 cases and 2,009 controls with follow-up in a collection of 415 cases and 2,006 controls and a further collection of 349 cases and 1,588 controls from a Han Chinese population. We identified three loci associated with VKH syndrome susceptibility (IL23R-C1orf141, rs117633859, Pcombined = 3.42 × 10(-21), odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, Pcombined = 2.97 × 10(-11), OR = 1.37; and HLA-DRB1/DQA1, rs3021304, Pcombined = 1.26 × 10(-118), OR = 2.97). The five non-HLA genes were all expressed in human iris tissue. IL23R was also expressed in the ciliary body, and EGR2 was expressed in the ciliary body and choroid. The risk G allele of rs117633859 in the promoter region of IL23R exhibited low transcriptional activation in a cell-based reporter assay and was associated with diminished IL23R mRNA expression in human peripheral blood mononuclear cells.
    Nature Genetics 08/2014; 46(9):1007-11. DOI:10.1038/ng.3061 · 29.65 Impact Factor
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    Chaokui Wang · Zi Ye · Aize Kijlstra · Yan Zhou · Peizeng Yang
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    ABSTRACT: Recent studies show that the aryl hydrocarbon receptor (AhR) is involved in immune responses. AhR is activated following interaction with its ligands, such as 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). In this study, we investigated the role of AhR activation by its endogenous ligands in the pathogenesis of ocular Behcet's disease (BD). The expression of AhR was significantly decreased in active BD patients as compared to inactive BD patients and normal controls. Both FICZ and ITE inhibited Th1 and Th17 polarization and induced the expression of IL-22 by PBMCs and by CD4(+)T cells in active BD patients and normal controls. Stimulation of purified CD4(+)T cells with FICZ or ITE caused a decreased expression of RORC, IL-17, IL-23R, and CCR6 and an increased phosphorylation of STAT3 and STAT5. The present study suggests that a decreased AhR expression is associated with disease activity in BD patients. The activation of AhR by either FICZ or ITE was able to inhibit Th1 and Th17 cell polarization. Further studies are needed to investigate whether modulation of AhR might be used in the treatment of BD.
    Mediators of Inflammation 06/2014; 2014:195094. DOI:10.1155/2014/195094 · 3.24 Impact Factor

Publication Stats

2k Citations
505.65 Total Impact Points

Institutions

  • 2008–2015
    • Chongqing Medical University
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2005–2010
    • Sun Yat-Sen University
      • State Key Laboratory of Oncology
      Guangzhou, Guangdong Sheng, China
  • 2002
    • Zhongshan University
      中山, Guangdong, China
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2001
    • Sun Yat-Sen University of Medical Sciences
      中山, Guangdong, China