寻常性银屑病患者表皮中DNA总体甲基化水平检测

目的通过检测寻常性银屑病患者表皮DNA总体甲基化水平,探讨DNA甲基化在银屑病发生发展过程中的作用。方法采用荧光比色法检测寻常性银屑病患者表皮DNA总体甲基化水平,与同一患者非皮损部位及健康对照者表皮进行对照研究,并分析其与病情严重程度的相关性。以PASI评分评估银屑病病情严重程度。结果在30例银屑病患者皮损、非皮损部位表皮及28名健康对照者表皮中检测到不同程度的DNA甲基化,分别为(4.92±2.12)%、(2.85±1.35)%和(2.32±0.99)%。银屑病患者皮损部位表皮DNA总体甲基化水平显著高于同一患者的非皮损部位(P<0.0001)及健康对照者(P<0.0001),而非皮损部位DNA总体甲基化水平与健康对照者之间差异无统计学意义(P>0.05)。银屑病患者皮损部位表皮中DNA总体甲基化水平与PASI评分之间存在显著相关性(P<0.0001)。结论寻常性银屑病患者表皮中DNA总体甲基化水平明显升高,且与疾病严重程度呈正相关。     

寻常型银屑病患者血清载脂蛋白A—Ⅰ及B—100测定

为了探讨银屑病患者易并发心血管疾病的原因，我们采用免疫定量法、酯法及三唑法分别对３０例寻常型银屑病患者血清载脂蛋白Ａ－Ⅰ、Ｂ－１００及胆固醇、甘油三酯进行了测定。结果表明，与对照组相比，患者组载脂蛋白Ａ－Ⅰ和甘油三酯正常，载脂蛋白Ｂ－１００和胆固醇升高（Ｐ均＜０．０５），且二者呈显著正相关（Ｐ＜０．０５），载脂蛋白Ａ－Ⅰ／Ｂ－１００比值降低（Ｐ＜０．０５），且与胆固醇呈显著负相关（Ｐ＜０．０５）。表明载脂蛋白Ｂ－１００升高及载脂蛋白Ａ－Ⅰ／Ｂ－１００比值降低导致了寻常型银屑病患者血清胆固醇升高和心血管疾病的发生。     

寻常型银屑病患者表皮HLA-C位点mRNA表达的研究

目的:检测寻常型银屑病患者表皮HLA-C位点mRNA的表达.方法:应用qReal-time-PCR技术检测46例寻常型银屑病患者皮损、非皮损表皮中的HLA-C位点mRNA的表达,与28名正常人皮肤表皮进行对照.结果:银屑病患者皮损、非皮损和正常人皮肤表皮中HLA-C 位点mRNA表达分别是0.0063±0.0070,0.0048±0.0037和0.0036±0.014.3组样本比较,银屑病患者皮损mRNA表达明显高于非皮损(P＜0.05),非皮损mRNA表达与正常对照比较无显著性差异.进行期皮损表皮的mRNA表达明显高于稳定期(P＜0.05).结论:寻常型银屑病患者HLA-C位点mRNA表达异常,可能与该病发病机制有关.     

DNA甲基化与银屑病相关基因的研究进展

DNA甲基化作为重要的表观遗传学现象之一,对基因的表达、细胞分化与增殖等发挥重要的调控功能.银屑病是一种由多基因多因素共同作用的具有遗传背景的复杂疾病,其组织病理特征为表皮过度增殖等表现.近年来关于DNA甲基化与银屑病相关基因p14、p16、p21、HLA-C、SHP-1基因的研究成为热点.概述DNA甲基化机制及主要的甲基化检测方法,并阐述银屑病相关基因的甲基化的研究现状.     

寻常性银屑病患者表皮p16INK4a基因启动子高甲基化与临床资料的相关性研究

目的：探讨斑块状银屑病患者表皮p16^INK4a基因启动子甲基化状态,并分析与其临床资料的相关性。方法：按银屑病皮损面积和严重度指数（PASI）评分评估患者病情严重程度。采用甲基化特异PCR（MAP）方法检测p16^INK4a甲基化状态。结果：①银屑病患者皮损和非皮损表皮p16^INK4a基因的甲基化率分别为32．14％（9／28）和7．14％（2／28）,皮损处明显高于非皮损处（P〈0．05）,正常对照组中无表皮p16^INK4a基因甲基化（0/38）;②进行期皮损表皮p16^INK4a基因的甲基化率明显高于稳定期皮损（P〈0．05）;③皮损表皮p16^INK4a基因甲基化阳性患者的PASI评分明显高于甲基化阴性患者（P〈0．05）。结论：斑块状银屑病患者皮损表皮p16^INK4a基因启动子甲基化率明显增高,并与皮损严重程度和活动性有关,提示p16^INK4a基因启动子高甲基化在银屑病的发病中可能起作用。     

寻常性银屑病患者表皮中DNA甲基化转移酶2和3a mRNA的表达

目的 检测寻常性银屑病患者表皮中DNA甲基化转移酶（DNMT2和DNMT3a）mRNA表达。方法 利用实时定量PCR技术检测2009年3月至2010年12月来自中国医学科学院皮肤病医院皮肤科及宜兴市人民医院皮肤科门诊的46例寻常性银屑病患者皮损和非皮损表皮以及来自中国医学科学院皮肤病医院皮肤外科的28例健康对照表皮中DNMT2和DNMT3a mRNA的表达。结果 在银屑病患者皮损、非皮损和对照组表皮DNMT2 mRNA表达水平（2-ΔΔCt值）分别是0.62 ± 0.02、0.36 ± 0.05和0.15 ± 0.11,皮损组明显高于非皮损组（t = 6.23,P < 0.01）,非皮损组明显高于对照组（t = 7.33,P < 0.01）;DNMT3a mRNA表达水平（2-ΔΔCt值）分别是0.85 ± 0.03、0.43 ± 0.04和0.18 ± 0.09,皮损组明显高于非皮损组（t = 5.66,P < 0.01）,非皮损组明显高于对照组（t = 8.62,P < 0.01）。结论 寻常性银屑病患者表皮DNMT2和DNMT3a mRNA均异常高表达。     

泛发性脓疱性银屑病与HLA-DQB1等位基因的相关性研究

目的 探讨山东汉族人泛发性脓疱性银屑病(GPP)与HLA-DQB1等位基因的相关性。方法 运用聚合酶链反应-序列特异性引物(PCR-SSP)法,对38例山东汉族人GPP与94例健康对照进行HLA-DQB1等位基因分型。结果 GPP患者组HLA-DQB10201、0603基因频率较对照组显著升高(OR=8.10,Pc=0.005;OR=5.06,Pc=0.013),而HLA-DQB10604基因频率较对照组明显降低(OR=0.08,Pc=0.039)。原有寻常性银屑病病史的GPP与HLA-DQB10201、0603强相关(OR=32.31,Pc=0.005;OR=12.42,Pc=0.005);而原无寻常性银屑病病史的GPP与HLA-DQB10602相关(OR=5.60,Pc=0.039)。结论 山东汉族GPP与HLA-DQB10201、0603等位基因高度关联,原有寻常性银屑病病史的GPP与原无寻常性银屑病病史的GPP具有遗传异质性。     

寻常性银屑病并发大疱性类天疱疮一例

患者女,80岁。因全身鳞屑性红斑10年,皮损加重伴剧痒1个月,脐窝出现水疱2 d,于2011年3月18日至我院皮肤科就诊……     

寻常性银屑病合并大疱性类天疱疮1例

1临床资料 患者男,50岁,躯干、肘、膝红斑鳞屑10余年,3月前在红斑基础上出现水疱,不易破溃,轻度瘙痒,而就诊于我院皮肤科.患者10年前无明显诱因躯干四肢起散在红斑、丘疹、鳞屑,伴瘙痒.     

北方汉族白癜风患者HLA－Ⅰ类抗原相关性研究

目的 探讨中国北方汉族人群中白癜风与ＨＬＡ－Ⅰ类抗原的相关性。方法 白癜风患者９５例,采用ＨＬＡ血清学分型技术检测ＨＬＡ－Ａ、Ｂ位点的抗原特异性,并与１００例正常人进行比较。结果 ①白癜风患者ＨＬＡ－Ａ２、Ａ１０、Ａ３０＋３１、Ｂ１３、Ｂ１５抗原频率显著增高（Ｐｃ〈０．０１）;ＨＬＡ－Ａ２８、Ｂ４６抗原频率显著降低（Ｐｃ〈０．０１）。②有明确家族史的白癜风患者ＨＬＡ－Ａ１０、Ｂ１３、Ｂ１５抗原频率     

Association of human leukocyte antigen class I antigens in Iranian patients with pemphigus vulgaris

There are a limited number of reports indicating the role of human leukocyte antigen (HLA) class I alleles in pemphigus vulgaris. This study was designed to highlight the association of HLA class I alleles with pemphigus vulgaris in Iran. Fifty patients with pemphigus vulgaris, diagnosed based on clinical, histological and direct immunofluorescence findings were enrolled into this study. The control group consisted of 50 healthy, age‐ and sex‐matched individuals. HLA typing of class I (A, B and C alleles) was carried out using polymerase chain reaction based on the sequence‐specific primer method. This study showed the higher frequency of HLA‐B*44:02 (P = 0.007), ‐C*04:01 (P < 0.001), ‐C*15:02 (P < 0.001) and ‐C*16:01 (P = 0.027) in the patient group, compared to the controls, while the frequency of HLA‐C*06:02 (P < 0.001) and ‐C*18:01 (P = 0.008) in the patients with pemphigus vulgaris was significantly lower than the controls. Regarding the linkage disequilibrium between HLA class I alleles, the HLA‐A*03:01, ‐B*51:01, ‐C*16:02 haplotype (4% vs 0%, P = 0.04) is suggested to be a predisposing factor, whereas HLA‐A*26:01, ‐B*38, ‐C*12:03 haplotype (0% vs 6%, P = 0.01) is suggested to be a protective factor. In conclusion, it is suggested that HLA‐B*44:02, ‐C*04:01, ‐C*15:02 alleles and HLA‐A*03:01, ‐B*51:01, ‐C*16:02 haplotype are susceptibility factors for development of pemphigus vulgaris in the Iranian population, while HLA‐C*06:02, ‐C*18:01 alleles and HLA‐A*26:01, ‐B*38, ‐C*12:03 haplotype may be considered as protective alleles.     

Telomere length,oxidative and epigenetic changes in blood DNA of patients with exacerbated psoriasis vulgaris

BackgroundThe pathogenesis of psoriasis vulgaris involves changes in DNA molecules, genomic instability, telomere attrition, and epigenetic alterations among them. These changes are also considered important mechanisms of aging in cells and tissues.ObjectiveThis study dealt with oxidation damage, telomere length and methylation status in DNA originating from peripheral blood of 41 psoriatic patients and 30 healthy controls.MethodsOxidative damage of serum DNA/RNA was determined immunochemically. Real-time PCR was used for the analysis of the telomere length. ELISA technique determined levels of 5-methylcytosine in blood cells' DNA.ResultsOxidative damage of serum DNA/RNA was higher in patients than in controls (median, 3758 vs. 2286 pg/mL, p < 0.001). A higher length of telomeres per chromosome was found in patients whole-cell DNA than in controls (3.57 vs. 3.04 kilobases, p = 0.011). A negative correlation of the length of telomeres with an age of the control subjects was revealed (Spearman’s rho = -0.420, p = 0.028). Insignificantly different levels of 5-methylcytosine in patients and controls were observed (33.20 vs. 23.35%, p = 0.234). No influences of sex, smoking, BMI, PASI score, and metabolic syndrome on the methylation status were found.Study limitationsi) A relatively small number of the participants, particularly for reliable subgroup analyses, ii) the Caucasian origin of the participants possibly influencing the results of the parameters determined, and iii) Telomerase activity was not directly measured in serum or blood cells.ConclusionThe study demonstrated increased levels of oxidized DNA/RNA molecules in the serum of patients with exacerbated psoriasis vulgaris. The results were minimally influenced by sex, the presence of metabolic syndrome, or cigarette smoking. In the psoriatic blood cells' DNA, the authors observed longer telomeres compared to healthy controls, particularly in females. Insignificantly higher global DNA methylation in psoriasis cases compared to the controls indicated marginal clinical importance of this epigenetic test performed in the blood cells' DNA.     

Association of HLA-A, -B, -C genes and TNF microsatellite polymorphism with psoriasis vulgaris: a study of genetic risk in Brazilian patients

This study investigated the genetic association of HLA class I genes and TNF-alpha microsatellites. HLA-A, -B, -C typing was carried out in 92 psoriasis vulgaris patients and 160 healthy individuals using a PCR-SSP method. 70 patients and 71 controls were typed for five microsatellite polymorphisms, TNFa-e. HLA-B*13 Cw*06, HLA-B*57 Cw*06 and HLA-B*39 Cw*12 haplotypes were found to be increased in patients with psoriasis type I when compared to controls, which could determine the susceptibility to development of psoriasis. TNFa4, TNFb1, TNFe1 and TNFa2 b1 c2 d4 e1 haplotypes showed a decreased frequency (p < 0.05) in psoriasis patients when compared to controls. HLA-B*13 allele and HLA-B*13 Cw*06, TNFa11 b4 c1 d3 e3 haplotypes showed increased frequencies (p < 0.05) in patients with type II psoriasis, which suggests susceptibility to the onset of psoriasis. Our results detected polymorphisms of the HLA class I and microsatellite TNF locus which could be markers of genetic predisposition to the disease.     

Investigation of 20 non‐HLA (human leucocyte antigen) psoriasis susceptibility loci in Chinese patients with psoriatic arthritis and psoriasis vulgaris

Background Recently, a number of non‐HLA (human leucocyte antigen) psoriasis genetic susceptibility loci have been identified through genome‐wide association studies, but data on their association with psoriatic arthritis (PsA) are lacking. Objectives To investigate recently identified psoriasis susceptibility loci in a cohort of Chinese patients with PsA, psoriasis vulgaris (PsV) and healthy controls. Methods Twenty single‐nucleotide polymorphisms (SNPs) from 20 loci were selected for genotyping in 379 patients with PsA, 595 patients with PsV and 1181 healthy controls using the MassARRAY platform (Sequenom, San Diego, CA, U.S.A.). Data handling, quality control and association were performed using PLINK software, v. 1.07. The Cochran–Armitage trend test was used to test the genotype–phenotype association. Results PsA showed a significant association with markers at TNIP1 (rs17728338, P = 2·20 × 10^?8), IL28RA (rs4649203, P = 5·04 × 10^?6), IL12B (rs2082412, P = 3·82 × 10^?5), ERAP1 (rs27524, P = 1·25 × 10^?3), PTTG1 (rs2431697, P = 1·22 × 10^?3) and GJB2 (rs3751385, P = 1·48 × 10^?3) when compared with the control group. In PsV a significant association was found for IL28RA (rs4649203, P = 9·53 × 10^?7), TNIP1 (rs17728338, P = 1·21 × 10^?4) and ERAP1 (rs27524, P = 1·17 × 10^?3). The allele frequencies were not statistically different between PsA and PsV except for SNPs at IL12B and ZNF816A with a nominal P‐value of 0·04 and 0·01, respectively. Conclusions This study provides evidence for the involvement of ERAP1, IL28RA, GJB2 and PTTG1 loci in PsA susceptibility and confirmed the previously reported association with PsA and PsV. These results support the hypothesis that genetic aetiology of psoriasis is the same in both PsA and PsV and also support the higher genetic component of PsA than PsV.     

胎盘型钙黏蛋白在寻常性银屑病患者血清和皮损中的表达及意义

目的探讨胎盘型钙黏蛋白（P-cadherin,P-cad）在寻常性银屑病发病中的作用和意义。方法选择寻常性银屑病患者40例,分别采用酶联免疫吸附法和免疫组化法检测患者血清和皮损中P-cad的表达,另40名正常人作为对照。结果寻常性银肩病患者血清中P-cad表达水平明显高于正常对照者（P〈0.01）,表达水平与病情严重程度呈正相关;寻常性银屑病患者皮损中P-cad在角质形成细胞（keratinocyte,KC）各层均有表达,而正常对照组仅在表皮基底层表达,表达水平差异有统计学意义,且与银屑病皮损严重程度指数（PASI）呈正相关。结论P-cad在寻常性银屑病呈高表达,且与疾病严重程度呈正相关。     

寻常性银屑病患者血清趋化因子CCL27的检测及临床意义

目的 检测寻常性银屑病患者血清CCL27水平并探讨其临床意义。方法 采用酶联免疫吸附法检测61例寻常性银屑病患者治疗前后和45例健康人血清CCL27水平。结果 61例寻常性银屑病患者血清CCL27水平为（670.02 ± 262.15） ng/L,健康人对照组为（373.10 ± 92.84） ng/L,两组差异有统计学意义（t ＝ 8.18,P ＜ 0.01）。进行期患者血清CCL27水平为（799.94 ± 214.54） ng/L,静止期为（422.57 ± 135.53） ng/L,两组差异有统计学意义（t ＝ 8.39,P ＜ 0.01）。经药物治疗8周后,银屑病患者PASI评分下降70％以上者36例,其CCL27水平明显下降,与治疗前比较,差异有统计学意义（t ＝ 9.95,P ＜ 0.01）;PASI评分下降不足70％者25例,CCL27水平与治疗前比较差异无统计学意义（t ＝ 1.84,P ＞ 0.05）。61例银屑病患者血清CCL27水平与PASI评分呈正相关（r ＝ 0.58,P ＜ 0.01）。结论 寻常性银屑病患者血清CCL27水平明显增高,并与疾病活动性相关。     

银屑病患者血清TNFα,HA,LN浓度变化与细胞粘附分子关系的研究

采用放射免疫分析法及流式细胞术检测了３５例银屑病和３０例健康人血清ＴＮＦα、ＨＡ、ＬＮ含量及外周血单一核细胞ＣＤ４４阳性细胞数。结果显示：银屑病患者血清ＴＮＦ、ＨＡＬＮＩ浓度均明显高于对照组,差异显著,ＣＤ４４一率亦显著增高,与对照组比较差异十分显著,银屑病患者ＣＤ４表达 上调与ＨＡ浓度增高呈正相关,ＨＡ与ＴＮＦ亦呈正相关。提示ＣＤ４４作为透明质本以体与ＴＮＦ、ＬＮ共同参与了银屑病发的病理过程。     

寻常性银屑病患者外周血单核细胞TLR4的表达及意义

目的：探讨寻常性银屑病患者外周血单核细胞Toll样受体4（Toll—likereceptor4，TLR4）的表达及其临床意义。方法：采用流式细胞术检测40例寻常性银屑病患者及30例正常人对照组外周血单核细胞TLR4的表达。结果：寻常性银屑病患者外周血中单核细胞TLR4的表达较正常人对照组明显增高（P〈0．01），而进展期的寻常性银屑病患者外周血中单核细胞TLR4的表达高于稳定期的患者的表达（P〈0．05）。结论：TLR4及其介导的天然免疫应答在银屑病发病机制中起重要作用，而寻常性银屑病患者外周血单核细胞TLR4表达与银屑病PASI评分无关，但与银屑病分期有关。