广东汉族SLE患者HLA-DR、DQ、DP基因多态性研究

目的：研究广东汉族SLE患与HJA-DQ、DR、DP的相关性。方法：采用聚合酶链反应-序列特异性引物(PCR-SSP)技术，对48例广东籍汉族SLE患和102例健康对照静脉血样本HJA-DQ、DR、DP等位基因多态性进行研究。结果：SLE患DQA1*0101等位基因频率显升高(RR=8．12，P=0．004)，DQA1*0302明显低于正常组(RR=0．09，P=0．005)。DQB1*0301基因频率明显低于正常组，两比较有显性差异(P＜0．01)。SLE患DR3(DRB1*0301-DRB1*0302)基因频率显高于正常组(x。=14．24，P＜0．01，RR=20．20)；DRw52(DRB3*0101-DRB3*0301)基因频率显高于正常组(x^2=20．346，P＜0．01)；DRWl4：DRBl*1402，DRB1*1403基因频率也显高于正常组(P＜0．05)；DR4(DRB1*0401-DRB1*0411)基因频率明显低于正常组(P＜0．01)，DR9(DRB1*0901)，DRw11(DRB1*1101-DRB1*1104)基因频率也显低于正常组(P＜0．01)，DPA1*0202等位基因频率显高于正常组(x^2=4．124，P＜0．05，RR=3．54)，SLE患DPA1*0201等位基因频率显低于正常组(x^2=4．595，P＜0．05，RR=0．37)。结论：提示HLA-DQA1*0302、DQB1*0301；DR4(DRB1*0401-DRB1*0411)，DR9(DPB1*0901)，DRw11(DRB1*1101-DRB1*1104)对SLE发病可能有一定保护作用。DPA1*0202为广东籍48例SLE患的易感基因，而DPA1*0201可能为其保护基因。     

银屑病易感基因最新研究进展

随着多基因疾病研究方法的不断进步,银屑病易感基因遗传学研究取得了很大进展.但多基因疾病往往涉及到多个基因的作用,虽然不断发现新的易感位点,但在寻找银屑病易感基因上还没有取得突破.就目前国际上银屑病易感基因的最新研究进展作一综述.     

银屑病家系易感基因定位的研究

目的:探讨银屑病易感基因与第4、6、17号染色体上7个微卫星标记的连锁关系,初步对汉族鲁系银屑病易感基因进行定位研究。方法:选择22个银屑病家系中75例患者和正常人51例。选择7个微卫星标记(STR):D6S276、D6S1610、D4S403、D4S424、D4S415、D17S949、D17S784,利用ABI3730测序仪进行电泳测序,并用与之配套的GeneScan、GeneMapper软件进行基因分型。利用GENEHUNTER软件对STR的基因分型数据进行连锁分析。结果:D17S949、D17S784位点的最大两点LOD值,最大两点NPL值均大于1(P<0.05),提示存在连锁关系。结论:染色体17q23~17q25区域内存在寻常型银屑病易感基因。     

链球菌感染诱发银屑病的研究现状

银屑病与链球菌感染的相关研究是近年来银屑病的研究热点之一。银屑病是一类由T淋巴细胞介导的自身免疫性疾病，链球菌抗原是T细胞的活化抗原之一，链球菌抗原可在易感人群中诱发或加重银屑病和使银屑病慢性持续存在。HLA的遗传多态性，如HLA—DR可能与此有关。本文就链球菌感染诱发银屑病的研究现状作一综述。     

北方汉族寻常型银屑病与HLA-DRB1及DQB1等位基因相关性研究

目的:探讨HLA-DRB1及DQB1等位基因与北方汉族寻常型银屑病相关性。方法:利用序列特异性引物-聚合酶链反应(PCR-SSP)分型技术,对63例寻常型银屑病患者和102例健康人的HIA-DRB!及DQB1等位基因进行检测。结果:(1)HLA-DRB1*070x、DRB1*1001及DOB`*020x等位基因与北方汉族寻常型银屑病呈正相关(P分别为0.001,0.005,0.009);HLA-DRB1*120x等位基因与北方汉族寻常型银屑病呈负相关(P=0.007)。(2)HLA-DRB1*070x及DQB1*020x等位基因仅与家族史阳性的早发型(Ⅰ型)银屑病发病相关(P<0.001)。(3)HLA-DRBq*1001等位基因频率在Ⅰ型及无家族史的晚发型(Ⅱ型)银屑病均显著性增高(P<0.05)。结论:(1)HLA-DRB1*070x、DRB1*1001及DQB1*020x等位基因可能是北方汉族寻常型银屑病的易感基因或与易感基因相连锁;HLA-DRB1*120x等位基因可能是阻止北方汉族人发生银屑病的保护基因。(2)Ⅰ型及Ⅱ型银屑病的遗传背景存在差异。     

关节病型银屑病与强直性脊柱炎易感基因关联研究

目的：对关节病型银屑病与强直性脊柱炎的易感基因进行关联分析,以期发现共同的易感基因。方法：以379例关节病型银屑病（PsA）、595例寻常型银屑病（PsV）及806例健康对照为样本,以Sequenom MassARRAY 系统为平台,对全基因组关联研究发现的强直性脊柱炎的9个易感基因SNP位点进行基因分型和数据分析。结果：ERAP1基因（rs27037,P=6.66×10-5,OR：1.43）、21q22.2（rs2242944,P =1.07×10-3, OR：0.73）及IL23R基因（rs1004819,P=4.58×10-3,OR：1.28）与PsA相关。ERAP1（ rs27037, P=1.56×10-4,OR：1.35）与PsV相关。ERAP1基因对于PsA和PsV的患病风险无差异。IL23R基因(rs1004819)及21q22.2（rs2242944）在PsA和PsV患病风险上存在中等程度的异质性（I2值分别为57.41和71.20）,但P值无明显差异（小于0.05）。 IL23R基因（rs11209032,p=1.57×10-3,OR:1.52）与PsA脊柱炎相关。结论：ERAP1基因、21q22.2区域及IL23R基因是PsA与强直性脊柱炎共有的易感基因。     

银屑病易感基因位点PSORS1的研究进展

银屑病是一种常见的多基因遗传性皮肤病,通过对不同群体的银屑病患者的基因样本进行全基因组扫描,确定了7个银屑病易感基因位点(PSORS1～PSORSS7),其中位于6p21染色体上的易感基因位点PSORS1是当前银屑病易感基因研究的热点,它包括三个银屑病候选基因:HLA-Cw6,CDSN,HCR.分别对这三个易感基因进行综述.     

银屑病相关miRNAs表达及其易感基因的研究进展

银屑病的发病是一种由多因素参与、多基因改变的复杂病变过程,多基因之间相互关系的研究也成为银屑病的一种研究趋势。研究发现,Micro RNA在银屑病的生理生化免疫等过程中发挥了重要的作用,在皮损组织中有表达异常,是银屑病发生、发展过程中的重要调控因素。而在易感基因方面,OMIM中现已收录了12个银屑病易感基因位点,其候选基因HLA、HCR、CDSN等的研究也日趋成熟。本文就银屑病相关Micro RNAs的表达以及银屑病的易感基因研究进展进行综述,为开展银屑病相关Micro RNAs与其易感基因之间关系的研究提供线索,为银屑病的早期诊断和预后提供新的思路,并在治疗方面提供新的药物靶点和治疗靶点。     

点滴型银屑病与链球菌感染关系的实验室研究进展

阐述了银屑病，尤其是点滴型银屑病与链球菌感染的着重，介绍了体内试验，血学、细胞学及治疗学等诸方面最新研究成果。     

染色体4q存在中国汉族人的银屑病易感基因

目的：确定在4号染色体长臂上是否存在中国汉族人寻常性银屑病易感基因。方法：用覆盖4号染色体长臂的12个微卫星标记对64个寻常性银屑病家系共372个个体（包括197例患者和175例非患者）进行基因组扫描研究，并用GENEHUNTER软件（2.0 Version)对基因分型结果进行参数和非参数连锁（NPL）分析。结果：（1）非参数连锁分析：两点连锁分析揭示D4S413和D3S1597的NPL值分别为2．04和2．23，对应的P值分别为0．021和0．014；多点连锁分析在染色体155．1－172．3cM的范围NPL值均大于3，在位点D4S413（157．9cM)处NPL值达最高，为3．44，相应的P值为0．00056。（2）参数连锁分析在显性遗传模式下，外显率10％，基因频率0．0062时在D4S1597位点处得出LOD值＝3．70，异质性LOD（HLOD）值＝4．35和较高的连锁家系比例α=85%。结论：染色体4q存在中国汉族人的寻常性银屑病易感基因。     

复发性生殖器疱疹患者外周血T细胞CD69和HLA-DR的表达

目的:探讨复发性生殖器疱疹(RGH)患者外周血CD69和HLA-DR分子在T细胞的表达。方法:采用免疫荧光三标记流式细胞术检测18例RGH患者在疾病发作期和静止期外周血T细胞上CD69和HLA-DR抗原的表达。结果:RGH患者外周血CD3+T细胞CD69的表达,较正常对照组明显升高(P<0.01);CD4+T细胞CD69的表达,在发作期为5.63±1.74,静止期为7.12±2.27,均比正常对照组明显升高,发作期与静止期相比差异有高度显著性(P<0.01);RGH患者外周血CD3+T细胞HLA-DR+的表达,亦显著高于对照组(P<0.01)。结论:单纯疱疹病毒感染诱导体内CD4+和CD8+T细胞活化、增殖,前者分泌多种抗病毒细胞因子,后者则分化为病毒特异性CD8+细胞毒T细胞,它们共同发挥着抗病毒作用。     

江苏、安徽籍汉族天疱疮患者HLA-DR基因的相关性研究

目的 探讨HLA-DR位点基因在天疱疮易感性中的作用。方法 用序列特异性引物-聚合酶链反应(PCR-SSP)方法,对61例寻常型天疱疮(PV)、37例红斑型天疱疮(PE)患者及57例正常对照者进行了HLA-DR等位基因的分型,并分析了DR基因在两组中的分布。结果 与正常对照组比较,PV患者组DR4、DRB1*14(*1401、*1404、*1405)基因频率明显增高,校正P值分别为<0.05及<0.01;PE患者组DR4、DRB1*14基因频率比对照组也显着增高,校正P值<0.05.对DR4阳性标本的组内基因亚型分型结果发现,PV组中DRB1*0403、DRB1*0406频率显着增高,校正P值<0.05;PE中DRB1*0406频率显着增高,校正P值<0.05.结论 本研究结果提示,DR4、DRB1*14基因可能是PV和PE的易感基因;HLA-DR基因在PV和PE的易感性方面所起的作用可能相似。     

HLA—DR抗原在斑秃皮损中的表达

目的：探讨斑秃的发病机理。方法：应用免疫组化的方法（SP法）观察了HLA－DR抗原在15例斑秃皮损中及8例正常头皮组织中的表达情况。结果：HLA－DR抗原在斑秃皮损毛囊角度形成细胞中明显表达，占60％（9／15）（P＜0．05）；HLA－DR抗原在正常头皮中未见表示。结论：HLA－DR抗原参与了斑秃发病，免疫功能紊乱可能是斑秃的发病因素。     

A case of baboon syndrome associated with group a streptococcal infection

We described a 21-year-old Japanese patient with sore throat, fever, and diffuse erythema on the neck, trunk, and limbs. Erythema markedly appeared on the neck, axillary, antecubital, and popliteal fossae. However, other skin signs of scarlet fever such as red strawberry tongue and linear petechial eruption did not appear. Before his visit to our clinic, he had been diagnosed as pharyngitis and treated with cefaclor 750 mg daily for six days. However, the symptoms did not improve. Oral prednisolone of 20 mg daily rapidly improved all the symptoms. Pharyngeal culture grew Streptococcus pyogenes that was sensitive to cefaclor. Laboratory findings showed elevated serum levels of antibody against streptolysin O. Together with the distribution of erythema, culture of Streptococcal pyogenes, and elevated anti-streptolysin O titer, the diagnosis of baboon syndrome associated with streptococcal infection was made. This seems to be the first report of baboon syndrome due to streptococcal infection.     

Management of long‐term therapy with biological drugs in psoriatic patients with latent tuberculosis infection in real life setting

Psoriatic patients with latent tuberculosis infection (LTBI) need a prophylaxis before starting a treatment with biological drugs. The aim of this study is to investigate the safety and efficacy of prophylaxis of LTBI in psoriatic patients receiving long‐term biological drugs. The study included 56 patients (42 male and 14 female) affected by moderate‐to‐severe psoriasis (mean PASI: 12.8 ± 6.9 SD) treated with anti‐TNF‐α and/or anti IL 12, 23 and/or anti‐CD11 drugs with a diagnosis of LTBI. LTBI diagnosis was based on tuberculin skin test and/or QuantiFERON TB Gold test positivity and chest X‐ray suggestive, without clinical, or microbiological evidence of active disease. All patients received prophylactic therapy for 9 months with isoniazid (INH) 300 mg/day, starting 3 weeks before the beginning of biological treatment. Fifty‐four patients completed prophylaxis with INH without any adverse events or intolerance; they continue the biological treatment without appearance of active tuberculosis. One patient developed tuberculosis pleurisy in course of treatment with etanercept. The infection has been treated and after a stable remission, treatment was restarted without tuberculosis reactivation. In this retrospective analysis, the prophylaxis of LTBI whit INH was effective and safe in longer follow‐up period.     

尖锐湿疣皮损角质形成细胞ICAM-1及HLA-DR表达的研究

目的:研究细胞间黏附分子-1(ICAM-1)及人白细胞分化抗原DR区(HLA-DR抗原)在尖锐湿疣(CA)发病中的作用。方法:采用免疫组织化学技术一链酶亲和素一生物素复合物法(SABC法)对比研究CA初发组、CA复发组及正常人角质形成细胞(KC)表面ICAM-1及HLA-DR抗原的表达。结果:CA初发组与复发组间ICAM-1及HLA-DR抗原表达无显著性差异(P>0.05)。病例组中KC表面ICAM-1及HLA-DR抗原表达有一定相关性(r=0.4316,P<0.05)。结论:CA患者病损处KC表面表达ICAM-1及HLA-DR抗原使局部细胞免疫状态发生变化,诱导T细胞在病损处聚集、活化,是有效地启动并参与局部免疫应答、促进CA病损消退的关键。     

Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis

The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case–control study involving 400 psoriasis patients who attended the Psoriasis and Photo‐medicine clinic in the National Skin Center of Singapore over a 1‐year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self‐administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49–169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33–4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.     

内蒙古汉族寻常型银屑病REL基因多态位点检测

目的：检测内蒙古汉族人寻常型银屑病（PsV）患者禽网状内皮组织增殖病毒癌基因V-Rel同源基因（REL）的多态性。方法：提取301例PsV患者及292例正常对照外周血DNA,利用连接酶检测反应检测REL基因区域的4个单核苷酸多态性（SNP）（rs702873、rs842636、rs13031237 和 rs13017599）。结果：PsV患者rs702873和rs842636的等位基因频率分别为0.126和0.128,对照组中分别为0.182和0.181,差异有统计学意义(P<0.05)且rs702873和rs842636间存在强连锁不平衡（D’=0.993,r2=0.980）。rs13031237和rs13017599等位基因频率在PsV患者和对照组中差异无统计学意义(P>0.05)。结论：REL基因位点（rs702873和rs842636）多态性可能与内蒙古汉族人PsV的易感性相关。     

Vitamin D receptor gene polymorphisms are associated with psoriasis susceptibility and the clinical response to calcipotriol in psoriatic patients

Psoriasis is a common genetic disease characterized by hyperproliferation and disordered maturation of keratinocytes. To date, many association studies between psoriasis and VDR gene have been conducted, but the results are controversial. Furthermore, vitamin D₃ analogue has anti-psoriatic activity; however, the clinical response is variable. This study was conducted to explore whether VDR gene polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients. A total of 110 patients and 183 controls were genotyped for VDR gene polymorphisms rs2228570, rs731236, rs1544410 and rs7975232 by LDR method. SNP-based and haplotype-based association analyses were subsequently performed. Patients with PASI < 3 were treated with calcipotriol ointment monotherapy. After 6 weeks of therapy, the correlations between efficacy and the genotypes of each polymorphism were evaluated. The results showed that for rs7975232, allele A was significantly over-represented in psoriasis patients relative to controls (39.09% vs. 27.05%, OR (95% CI) = 1.731 (1.213-2.471)), and compared with the reference CC genotype, the following ORs were observed: AA genotype OR = 2.404 (95% CI: 1.085-5.328; P = .034) and GA genotype OR = 2.143 (95% CI: 1.283-3.579; P = .005). Haplotype analyses showed that the rs2228570/rs731236/rs1544410/rs7975232 CTGA was significantly over-represented in psoriasis patients compared with controls (OR (95% CI)=1.907 (1.132-3.214); P = .020). Among the patients with PASI < 3, the response rates to calcipotriol were significantly higher in patients with rs7975232 CC genotypes than in those with other genotypes (x² = 9.172, P = .010). These data suggest that VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients.