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。     

大疱及疱疹性皮肤病

20 0 3 0 91 9　HLA DRB1、DQA1、DQB1基因与上海地区类天疱疮的易感性 /金岩 (复旦大学华山医院皮肤科 )…∥复旦学报 . 2 0 0 3 ,3 0 (1 ) . 2 0～ 2 3采用PCR SSOP方法对上海地区汉族 5 6例BP患者和 1 5 0例健康对照者进行了HLA DRB1、DQA1、DQB1位点等位基因分型。结果发现HLA DRB1 1 0 0 1与DQB1 0 5 0 1紧密连锁 ,其基因频率BP组与对照组比较明显增高 ;DRB1 0 4与DQB1 0 3 0 2紧密连锁 ,其基因频率与对照组比较也明显增高 ;DRB1 1 2基因频率BP组与对照组比较明显降低。因此DRB1 1 0 0 1、DRB1 0 4可…     

HLA—DRB1等位基因多态性与白塞病的相关性研究

目的：分析HLA—DRB1等位基因多态性与白塞病（BD）的相关性。方法：应用LABTypeTMSSO法对43例BD患者及120例正常对照组的HLA—DRB1等位基因进行检测。结果：与正常对照组相比,BD患者HLA—DRB1＊14基因频率明显增高（P〈0．05）,而HIA—DRB1＊15基因频率明显降低（P〈0．05）。HLA-DRB1等位基因与BD的临床表现具有一定的相关性。结论：HLA—DRB1＊14可能是BD的易感基因,HLA—DRB1＊15可能是BD的保护性基因。     

中国北方汉族泛发型白癜风与HLA—DRB1等位基因的相关性

目的：探讨HLA—DRBI等位基因与中国北方汉族泛发型白癜风的相关性：方法：采用聚合酶链反应-序列特异引物（PCR—SSP）技术检测34例北方汉族泛发型白癜风患者的HLA—DRBI等位基因。结果：与262例正常对照组相比较，泛发型白癜风患者HLA—DRB1＊0701／02、DRB1＊1201／02基因频率显著增高（Pc〈0．0001），HLA—DRB1＊0901、DRB1＊11基因频率降低（但经校正后Pc〉0．05）；有明确家族史的患者HLA—DRB1＊1201／02基因频率显著增高（Pc〈0．0001）；无家族史者HLA—DRB1＊0701／02基因频率显著升高（Pc〈0．0001），DRB1＊1201／02基因频率显著增高（经校正后Pc〉0．05），DRB1＊0901基因频率降低（经校正后Pc〉0．05）：结论：中国北方汉族人群，HLA—DRB1＊0701／02、DRB1＊1201／02等位基因可能与泛发型白癜风的发病有关，而DRB1＊0901、DRB1＊11等位基因可能是防止其发病的“保护因子”，为进一步揭示泛发型白癜风的易感基因及免疫遗传发病机制提供线索。     

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。     

山东地区汉族大疱性类天疱疮与HLA-DR,DQB1基因的相关性研究

目的探讨HLA-DR,DQB1位点基因在大疱性类天疱疮(BP)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49例BP患者及70例正常对照者进行了HLA-DR,DQB1等位基因的分型,并分析了上述基因在两组中的分布。结果与正常对照组比较,BP患者组DRB1*10基因频率明显增高(校正P值<0.05);DRB1*04-DQB1*0302连锁体频率、DRB1*10-DQB1*0501连锁体频率在BP组均显著高于对照组;DRB1*04在黏膜损害及大剂量皮质类固醇激素用量组显著增高。结论HLA-DR10(DRB1*10)可能是中国汉族BP的易感基因。DRB1*04-DQB1*0302连锁体、DRB1*10-DQB1*0501连锁体可能为汉族BP的易感连锁体。     

梅毒患者与HLA—DRB1等位基因相关性研究

目的：检测山东汉族梅毒患者与HLA-DRB1等位基因的相关性。方法：应用聚合酶链反应一序列特异性引物技术（PCR—ssp）对196例山东汉族梅毒患者与500例山东汉族正常对照的HLA-DRB1等位基因表现频率进行检测。结果：患者组DRB1＊14等位基因的出现频率高于对照组（P〈0．05）;DRB1＊16等位基因的出现频率与对照组无显著差异（P〉0．05）。结论：HLA—DRB1＊14等位基因可能是梅毒的易感基因。     

山东地区汉族关节病型银屑病与HLA—DRB1、DQB1的相关性研究

目的：探讨mA—DRB1、DQB1位点基因与关节病型银屑病的相关性。方法：用序列特异性引物一聚合酶链反应（PCR—SSP）方法，对41例关节病型银屑病患者进行了HLA—DRB1、DQB1等位基因的分型，并分析了上述基因在各组中的分布。结果：关节病型银屑病患者组DRB1＊07、DQB1＊0201频率较正常对照组增高；多关节炎型银屑病患者组DRB1＊07、DQB1＊0201以及DRB1＊04基因频率比正常对照组显著增高。结论：HLA—DRB1＊07、DQB1＊0201可能是山东地区汉族关节病型银屑病的遗传标志；具有银屑病易感基因的个体，携带HLA—DRB1＊04基因时，患多关节炎型银屑病的危险性可能增加。     

大疱及疱疹性皮肤病

20 0 2 30 84　汉族红斑型天疱疮与 HLA- 类基因相关性研究 /周淑华 (中国医科院皮研所 )…∥中国皮肤性病学杂志 .- 2 0 0 2 ,16 (3) .- 14 5对象为汉族红斑型天疱疮 (PE)患者 37例 ,对照组为 5 7例 (DR基因 )和 5 3例 (DQB1基因 )与患者同地区、无血缘关系的健康人。采用 PCR序列特异性引物 (PCR- SSP)法检测 HL A- DR、DQB1等位基因的分型。结果 :与正常对照组比较 ,PE患者组 DR4(DRB1*0 4 0 6 )、DRB1* 14、DQB1* 0 30 2、DQB1* 0 5 0 3基因频率比对照组显著升高。认为 ,HL A- DRB1* 14、DQB1* 0 5 0 3可能是汉族 PE患者易感的单倍型。图 1表 2参 9　 (刘彤 )2 0 0 2 30 85　家族性良性慢性天疱疮合并尖锐湿疣 2例/邢有兰 (天津市长征医院皮肤科 )…∥中国皮肤性病学杂志 .- 2 0 0 2 ,16 (3) .- 190例 1女 ,38岁 ,颈、腋窝、乳房下、腹股沟、外阴部红斑、糜烂 15年。体检见上述部位多处红斑、水疱、糜烂及结痂...     

SLE患者抗U1 RNP抗体与HLA-Ⅱ类基因的相关性分析

目的 探讨云南汉族系统性红斑狼疮（SLE）患者抗U1RNP抗体与HLA－DRB1、DQA1、DQB1等3位基因及单体型的相关性。方法 采用多聚酶链反应－序列特异性引物（PCR－SSP）技术对63例云南汉族SLE患者进行DRB1、DQA1、DQB1基因分型。结果 抗U1RNP抗体阳性的SLE病人中DQA1＊0101及DR15－DQA1＊0102－DQB1＊0601单体型频率亦显著增高（P＝0．040，P＝0．000）。结论 云南汉族SLE抗U1RNP抗体的产生与DQA1＊0101等位基因及DR15－DQA1＊0102－DQB1＊0601单体型相关。     

Human leukocyte antigen genotypes and antibody profiles associated with familial pemphigus in Japanese

Previous population-based, genetic studies have shown that human leukocyte antigen (HLA) class II loci such as HLA-DR4 (DRB1*04) and HLA-DR14 (DRB1*14) alleles are consistently associated with the occurrence of pemphigus vulgaris (PV) in Japanese as well as other ethnic populations. Among PV-related HLA-DRB1 alleles (*0406, *1401, *1405, *1406) in Japan, HLA DRB1*1405 and DRB1*0406 were found to be associated with both PV and pemphigus foliaceus (PF) phenotypes. We report four familial cases of pemphigus in two unrelated families, together with analysis of their HLA-DR and -DQ alleles, and their antibody profiles. One family comprised a woman with PF and her mother with PV: both patients shared a HLA haplotype of A31(19), B54(22), CW1 and DRB1*1405. Another family included two sisters with PF and PV, respectively: both of these patients shared a DRB1*1405-DQA1*0104-DQB1*0503 haplotype. Clinicopathological and serological monitoring revealed that the elder sister with PF presented with a PV phenotype later, and gained anti-desmoglein (Dsg)3 antibodies in addition to having a low titer of anti-Dsg1 antibodies. Conversely, the younger sister with PV developed PF with only anti-Dsg1 antibody detected. These results indicate that an HLA-DRB1*1405 (DQB1*0503) haplotype may confer susceptibility to both PV and PF, and that genetic susceptibility alone is not always responsible for the clinical phenotype and autoantibody profile.     

Genotyping for HLA-A, B and C alleles in Japanese patients with pemphigus: prevalence of Asian alleles of the HLA-B15 family

BACKGROUND: There have been only limited reports on major histocompatibility complex class I antigens in pemphigus. OBJECTIVES: To characterize HLA-A, B and C class I alleles by genotyping in Japanese patients with pemphigus, and to analyse the possible association of class I alleles with disease susceptibility within a relatively homogeneous ethnic population. METHODS: Alleles of HLA-A, B and C, and DRB1 and DQB1 loci were fully determined in 51 Japanese patients with pemphigus. RESULTS: Asian alleles of the HLA-B15 family, including the allele B*1507, which was significantly increased in comparison with normal controls, were prevalent in patients with pemphigus vulgaris (PV). The prevalence of B*15 alleles in patients with PV was not due to linkage disequilibrium with HLA-DR4 or DR14 alleles, which have been shown to confer strong susceptibility to PV across racial barriers. In contrast to the unique distribution of the HLA-B alleles, HLA-A and C alleles were unremarkable in patients with PV when compared with normal control subjects. CONCLUSIONS: These results suggest that there may be differences in the ethnic concentrations of different HLA-B alleles in patients with PV.     

Common human leukocyte antigen alleles in pemphigus vulgaris and pemphigus foliaceus Italian patients.

Pemphigus refers to a group of autoimmune blistering skin diseases, mainly identified as pemphigus vulgaris and pemphigus foliaceus, both characterized by the presence of autoantibodies against keratinocyte adhesion molecules, leading to loss of cell-cell adhesion with consequent blister formation. Pemphigus vulgaris is reported to be associated with human leukocyte antigen DR4 and/or DR6 whereas no data are available on pemphigus foliaceus, except for the endemic Brazilian form (fogo selvagem), which is reported to be associated with DR1 and DR4. We here report human leukocyte antigen molecular typing on a total of 87 patients, 61 with pemphigus vulgaris and 26 with pemphigus foliaceus, versus 128 healthy matched controls. Generic typing showed an increase of DRB1*04 and DRB1*14 and a decrease of DRB1*07 in both pemphigus vulgaris and pemphigus foliaceus patients. Molecular subtyping of DR4+ and DR14+ subjects showed a highly significant association between the DRB1*1401 and both pemphigus vulgaris (p < 0.0001) and pemphigus foliaceus patients (p < 0.0001) together with a significant increase of the linked DQB1*0503 (pemphigus vulgaris p < 0.0001; pemphigus foliaceus p < 0.0001). Moreover, whereas the association between DRB1*0402 and pemphigus vulgaris (p < 0.0001) has been confirmed, no significant association between a specific allele of the DR4 group and pemphigus foliaceus, has been found. Therefore, at least in Italian patients, pemphigus vulgaris and pemphigus foliaceus share DRB1*1401 and DQB1*0503, as susceptible human leukocyte antigen alleles, whereas DRB1*0402 is only found associated with pemphigus vulgaris. The observation that both diseases, pemphigus vulgaris and pemphigus foliaceus, carry the same susceptible human leukocyte antigen alleles has been interpreted as a common genetic background predisposing to pemphigus as, like in other autoimmune disorders, it is not sufficient to explain the onset of the disease on the basis of the sole aforementioned alleles. Other linked genes and/or environmental factors should play a facilitating role in the outbreak of pemphigus, either pemphigus vulgaris or pemphigus foliaceus.     

HLA-DRB1等位基因与四川汉族人寻常型天疱疮的相关性研究

目的 探讨HLA-DRB1等位基因与四川汉族人寻常型天疱疮的相关性.方法 采用聚合酶连反应-序列特异性引物(PCR-SSP)对19例四川汉族寻常型天疱疮患者和25例健康对照组进行低分辨和高分辨HLA-DRB1等位基因分型,计算各等位基因频率.采用x2检验比较两组等位基因频率.结果 在寻常型天疱疮患者和健康对照者中共检出9种低分辨DRB1等位基因和19种高分辨DRB1等位基因.与健康对照组相比,寻常型天疱疮患者DRB1*14等位基因频率(39.47％,15/38)及DRB 1*1405等位基因频率(15.79％,6/38)均显著高于健康对照组[8.00％(4/50),2.00％(1/50)],差异均有统计学意义(x2=17.43、4.25,均P＜0.05).结论 DRB1*14可能是四川汉族寻常型天疱疮患者的常见易感基因,其中DRB1*1405与寻常型天疱疮最具有相关性.     

特应性皮炎与HLA-DRB1 DQB1基因的相关性研究

目的探讨HLA-DRB1和DQB1位点基因与汉族特应性皮炎的相关性。方法用序列特异性引物-聚合酶链反应(PCR-SSP)方法,对59例特应性皮炎患者(来自27个家系)和60例正常对照者进行了HLA-DRB1和DQB1等位基因的分型,并分析了DRB1和DQB1基因在各组中的分布。结果特应性皮炎患者组DRB1*15,DR7,DQB1*0601等位基因频率较正常对照组增高(P<0.05);特应性皮炎患者组DQB1*0302频率较正常对照组降低(P<0.05)。特应性皮炎家系成员中对屋尘螨抗原皮试阳性者HLA-DR7等位基因频率较皮试阴性者均显著增高(P<0.05)。结论特应性皮炎的发病可能与DRB1*15,DR7,DQB1*0601相关;DQB1*0302对特应性皮炎的发病可能起保护作用。HLA-DR7在限定对屋尘螨抗原特异性IgE反应过程中起重要作用。     

汉族红斑型天疱疮与HLA-Ⅱ类基因的相关性研究

目的 探讨HLA-DR、DQB1位点基因在红斑型天疱疮（PE）易感性中的作用。方法 用聚合酶链反应-序列特异性引物（PCR-SSP）方法，对37例红斑型天疱疮患者进行了HLA-DR、DQB1等位基因的分型，并分别与57例和53例作了对照。结果 与正常对照组比较，PE患者组DR4（DRB1*0406）、DRB1*14、DQB1*0302、DQB1*0503基因频率比对照组显著增高。结论 HLA-DRB1*14、DQB1*0503可能是汉族PE患者易感的单倍型。     

The association between HLA DR, DQ antigens, and vulval lichen sclerosus in the UK: HLA DRB112 and its associated DRB112/DQB10301/04/09/010 haplotype confers susceptibility to vulval lichen sclerosus, and HLA DRB10301/04 and its associated DRB10301/04/DQB10201/02/03 haplotype protects from vulval lichen sclerosus

Lichen sclerosus (LS) is considered to have an immunogenetic background. Several small studies, using serological typing, have reported that HLA-DR11, DR12, and DQ7 were increased in LS, with DR17 less frequent. This study aimed to validate and detect new HLA-DR and DQ associations with LS in females and its characteristic clinical parameters. The cases, 187 female LS patients, and 354 healthy controls were all UK North Europeans. PCR-sequence specific primers method was applied to genotype the HLA-DR, DQ polymorphisms that correspond to 17 serologically defined DR and seven DQ antigens. Statistical analysis was performed with two-tailed Fisher's exact test with Bonferroni adjustment (p value after Bonferrroni adjustment, Pc). We found increased frequency of DRB1*12 (DR12) (11.2%vs 2.5%, pc < 0.01) and the haplotype DRB1*12/DQB1*0301/04/09/010 (11.2%vs 2.5%, p < 0.001, pc < 0.05), and a lower frequency of DRB1*0301/04 (DR17) (11.8%vs 25.8%, pc < 0.01) and the haplotype DRB1*03/DQB1*02DRB1*0301/DQB1*0201/02/03 (11.2%vs 24.6%, pc < 0.0001) in patients compared with controls. HLA DR and DQ antigens were not associated with time of onset of disease, site of involvement, structural changes of genitals, and response to treatment with potent topical steroids. In conclusion, HLA-DR and DQ antigens or their haplotypes appear to be involved in both susceptibility to and protection from LS.     

HLA-DR and DQ polymorphisms in bullous pemphigoid from northern China

Bullous pemphigoid (BP) is an autoimmune disease mediated by autoantibodies against hemidesmosome components. This study used PCR-sequence-specific primers to genotype polymorphisms in HLA-DR and DQ in 25 BP patients and 57 normal controls from northern China. We found lower frequencies of DRB1*08 (DR8) and DRB1*08/DQB1*06 (DR8/DQ6) haplotypes in BP patients than in controls (4.08% vs. 15.19% and 1.54% vs. 13.82%, respectively; P < 0.05), suggesting a protective role for DR8 and DR8/DQ6 haplotypes in BP patients from northern China; there were no statistical differences among other alleles tested. This result is strikingly different from previous reports that DQB1*0301 is associated with BP in Caucasian patients and DRB1*1101, DQB1*0302, DRB1*04/DQA1*0301/DQB1*0302 and DRB1*1101/ DQA1*0505/DQB1*0302 with Japanese BP patients. Ethnic differences in the polymorphic composition of the HLA-DR and DQ genes may influence genetic susceptibility to BP.     

Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles

Background  Pemphigus foliaceus is an autoimmune blistering skin disease that partly results from genetic factors, especially human leucocyte antigen (HLA) class II genes.
Objectives  The aim of the study was to determine the HLA DR/DQ markers of susceptibility and protection in the Tunisian endemic form.
Methods  Genomic DNA from 90 patients with pemphigus foliaceus recruited from all parts of the country and matched by age, sex and geographical origin with 270 healthy individuals, was genotyped.
Results  Firstly, when the whole patient population was studied, DRB1*03 , DQB1*0302 and DRB1*04 alleles were significantly associated with the disease while a significant decrease of, in particular, DRB1*11 and DQB1*0301 was observed in patients compared with controls. DRB1*0301 was the dominant allele in DR3-positive patients and controls, while DRB1*0402 was found in 42% of DR4-positive patients. Secondly, when the HLA DR/DQ allele distribution was studied after dividing patients according to their geographical origin, the southern group, which consisted exclusively of patients with the endemic form of the disease, showed the same associations as the whole pemphigus foliaceus population, particularly with DRB1*03 . In the northern group, only the DRB1*04 and DQB1*0301 alleles were found to be associated. Interestingly, anti-desmoglein 1 antibody-positive healthy controls did not carry susceptibility alleles but, in contrast, most carried negatively associated alleles.
Conclusions  These observations indicate that a particular genetic background characterizes the Tunisian endemic form of pemphigus foliaceus and that HLA class II genes control the pathogenic properties of the autoimmune response rather than the initial breakage of B-cell tolerance.