Polymorphisms of HLA-DR and -DQ genes in Japanese patients with bullous pemphigoid

Bullous pemphigoid (BP), an autoimmune skin disease of the elderly, is mediated by autoantibodies that bind to hemidesmosomes of epidermal basal cells. This study investigated BP-associated HLA-DR and -DQ genes among Japanese patients. We analyzed HLA-DR and -DQ genes among 23 Japanese BP patients based on the polymerase chain reaction-restriction fragment length polymorphism. Eighteen of these 23 patients (78%) carried at least one allele of HLA-DRB1*04 or DRB1*1101, with significant increases in HLA-DRB1*04 (*0403, *0406)/DQA1*0301/DQB1*0302 and DRB1*1101/DQA1*0505/DQB1*0302 haplotypes as well as the individual alleles DRB1*1101 and DQB1*0302 (corrected p < 0.05 for each comparison), when compared to control subjects. These data differ from the accepted DQB1*0301 (DQ7) association with the same disease among Caucasians. These findings indicate that different HLA class II haplotypes genetically influence susceptibility to BP among different ethnic groups. Our findings, together with previous reports on Caucasian patients with the pemphigoid group of bullous diseases, suggest that HLA-DRB1 molecules might participate in the regulation of autoimmune responses to BP antigens.     

Class II major histocompatibility complex typing across the ethnic barrier in pemphigoid gestationis. A study in Mexicans

BACKGROUND: Pemphigoid gestationis (PG), also called herpes gestationis, is a rare autoimmune disease of pregnancy or puerperium (estimated 1 out of 50,000 pregnancies among Caucasians). A previous series has demonstrated an association of PG with human leukocyte antigen (HLA)-DR3 or HLA-DR4 haplotypes. While these haplotypes are most commonly found in individuals of European ancestry, they have also been found in African-American patients affected with PG. PG has rarely been reported in other ethnic groups, and the HLA association in non-Europeans has not been examined. METHODS: We have characterized eight patients of Mexican ancestry who have PG by clinical, histologic, and immunofluorescence criteria. Class I and class II major histocompatibility complex (MHC) antigens were studied by standard microlymphocytotoxicity assays. Class II MHC antigens were further studied by polymerase chain reaction (PCR) amplification of HLA-DRB1, DQA, and DQB genes and allele-specific oligonucleotide hybridization. For comparison purposes, we used results obtained from a group of 100 ethnically matched healthy individuals. RESULTS: We found that all eight patients had the HLA-DR3/DR4 phenotype; all HLA-DR3 haplotypes were HLA-DRB1*0301, DQA1*0501, and DQB1*0201, whereas half of the HLA-DR4 haplotypes were from the DRB1*0401 subtype and the other half were DRB1 *0407. CONCLUSIONS: These results suggest that, in Mexicans, the genetic susceptibility for the development of PG is strongly influenced by the genetic admixture of Caucasian origin, and the role of class II MHC antigens in the pathophysiology of this disease is confirmed.     

Pemphigus vulgaris in distant relatives of two families: association with major histocompatibility complex class II genes

We describe major histocompatibility complex (MHC) class II gene haplotypes in two extended families, each of which has two members with pemphigus vulgaris (PV). One family is of Ashkenazi Jewish descent and the other family of English–Scottish descent. In one family the patients arc distant relatives; in the other, both share the same mother but have different lathers. The affected relatives in the two families have never shared a common environment and live in distant states. All four PV patients, regardless of whether they were of Ashkenazi Jewish or of English–Scottish descent, had the same haplotype, namely HLA-DRB1*0402, DQA1 *0301, DQB1*0302. Thus the PV patients, even though distantly related within a family, had the same MHC class II haplotype previously documented in Jewish patients. This observation further supports the concept that PV may result from an enhanced genetic susceptibility or predisposition to the disease.     

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.     

Class II MHC typing in pemphigoid gestationis

Pemphigoid gestationis (PG) is a rare, autoimmune skin disease associated with pregnancy or the immediate postpartum period, previously shown to be associated with the HLA class II antigens DR3 and DR 4. Advances in molecular analytical techniques now allow the identification of HLA alleles previously difficult to define by serological assays. Unsuspected polymorphism within the HLA-DR 3 and DR 4 classes can, therefore, be identified. The aim of our study was to apply these newer techniques to the question of genetic predisposition in PG by re-evaluating the association with DR 3 and by studying a possible link with DQ. We have investigated by restriction fragment length polymorphism, the DQA, and by sequence specified oligonucleotide probing the DQB and DRB 1 (HLA DR) specificities of 41 women with immunofluorescence-confirmed PG. The principal finding of this study is that there is an association between PG and DRB 1*0301 (DR3) and DRB 1*0401/040X (DR4). Although there is also an increase (P= 0.06) in the concurrent presence of both antigens, this appears to be due to the association with either antigen alone. We also found an increase in the frequency of DQA1*2 (P= 0.016 vs. control) and a decrease in frequency of DQB 1*0201 (P= 0.022 vs. controls) and DQB1*0602 (P= 0.026 vs. controls).     

Association between psoriasis vulgaris and MHC-DRB, -DQB genes as a contribution to disease diagnosis

We analyzed 100 control individuals and 60 patients with psoriasis vulgaris from the population of Campinas, Brazil. Typification of class II HLA alleles (HLA-DRB1-5 and -DQB1) was carried out through the DNA/PCR/SSP at medium and high resolution. DNA was extracted through a salting-out procedure: 13 DRB1 alleles, 3 DRB3 alleles, 1 DRB4 allele, 2 DRB5 alleles, and 5 DQB1 alleles were identified at a medium resolution using the PCR/SSP, and 45 DRB1 alleles were identified at a high resolution in analyzed patients. Results showed associations with psoriasis vulgaris: positive associations HLA-DRB3*02 (p < 0.05, chi(2) = 5.10, RR = 2.14); HLA-DRB1*0102 alleles (p < 0.05, RR = 5.44). Negative associations were found for HLA-DRB4*01 (chi(2) = 3.23, RR = 0.55) and HLA-DRB1*1302 alleles (p < 0.05, RR = 0.23). The haplotypes revealed positive association for HLA-DRB1*0102/DQB1*05 (p < 0.05, RR = 5.44) and HLA-DRB1*0701/DQB1*03 alleles (p < 0.02, RR = 9.00). These findings suggest a possible association of the DRB1 allele with the group of patients showing an early onset of the illness, as well as an association with haplotypes HLA-DRB1*0102/DQB1*05 and HLA-DRB1*0701/DQB1*03.     

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.     

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。     

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.     

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。     

Three different autoimmune bullous diseases in one family: is there a common genetic base?

We report an unusual familial occurrence of autoimmune bullous diseases. Three members of a family suffered from three different autoimmune bullous diseases: pemphigus vulgaris (PV), linear IgA disease (LAD) and cicatricial pemphigoid (CP). The HLA type was determined in five family members: all were positive for HLA-DQ5/DR6, which is reported to be associated with susceptibility to PV. The CP patient was DQ7(3) positive, which is in concordance with enhanced susceptibility to ocular CP and CP. The LAD patient was B8 and DR3 negative but positive for HLA-A1. Our study supports the hypothesis that there is a genetically transmitted susceptibility to autoimmune bullous diseases but that additional factors seem necessary actually to develop a particular disease.     

Mucous membrane pemphigoid: HLA-DQB1*0301 is associated with all clinical sites of involvement and may be linked to antibasement membrane IgG production

BACKGROUND: Class I human leucocyte antigens (HLA) -A, -B, -Cw and class II HLA-DRB1, -DQB1 alleles were determined in 131 British Caucasian patients with mucous membrane pemphigoid (MMP) using serological and DNA-based methods. OBJECTIVES: To analyse the class I and II alleles expressed in well-defined clinical and immunopathological subgroups of MMP, in order to establish whether specific alleles or haplotypes might in part explain disease susceptibility, clinical sites of involvement or disease severity. METHODS: Subgroups of patients were analysed according to the following clinical criteria: age of onset, sex, sites of clinical involvement (oral, ocular, skin, nasal, genital, pharyngeal, oesophageal, laryngeal, perianal), disease severity and history of autoimmune disease. Subgroups were also analysed according to the following immunopathological criteria: autoantibody profile, the presence of circulating antibasement membrane IgG or IgA antibodies and the detection of target basement membrane zone (BMZ) antigens (BP230 and BP180) by IgG autoantibodies. RESULTS: Class I HLA typing showed no significant disease or subgroup associations. Class II DRB1 typing showed a significantly increased allelic frequency in MMP vs. controls for DRB1*11 (RR = 2.08, Pc < 0.0000056). For DQB1, MMP vs. controls, there was a significantly increased allelic frequency for DQB1*0301 (Pc < 0.00000028) in both males and females; all clinical sites of involvement, with the exception of laryngeal, oesophageal and perianal sites and in patients with detectable circulating anti-BMZ IgG compared with those negative for IgG (P < 0.0096, Pc < 0.019). A positive trend was noted in patients with ocular involvement compared with no ocular involvement and in patients with a clinical score > or = 10 compared with < 10. We found no difference in DQB1*0301 allele frequency between subgroups with or without BP180 or BP230 target antigens. Haplotype frequencies showed an increase in DRB1*04, DQB1*0301 (Pc < 0.000066) and DRB1*11, DQB1*0301 (Pc < 0.000002) among patients compared with controls. CONCLUSIONS: The DQB1*0301 allele confers a predisposition to all subgroups of MMP and may have a role in T-cell recognition of basement membrane antigens, resulting in the production of anti-BMZ IgG autoantibodies. The positive trend between increased allelic expression of DQB1*0301 in patients with ocular disease and in those with a higher clinical score, further suggests a role for this allele in disease severity.     

HLA Haplotypes and Class II Molecular Alleles in Argentinian Patients with Pemphigus Vulgaris

Background: Pemphigus is a group of chronic blistering autoimmune diseases of which pemphigus vulgaris (PV) is the more frequent clinical form. The association of PV with the HLA serotypes suggests that there is a genetic predisposition to the disease. Objectives: To determine the frequency of class I and class II HLA antigens and the allelic variants of the class II HLA antigens, DR and DQ, in patients with PV and to determine the relative risk. Methods: An observational, prospective, transverse, and controlled study carried out between 1995 and 1999. Forty-seven patients with a diagnosis of PV and a control sampling of 199 unselected individuals from the same ethnic group were included. The HLA alleles were determined by polymerase chain reaction. Results: No significant associations were detected between HLA A, B, or C and our patients. The DR and DQ molecular alleles positively associated with PV were two different haplotypes: DRb1* 0402/DQb1* 0302 and DRb1* 1401/DQb1* 0503. Conclusions: In patients with the haplotype DRb1* 0402/DQb1* 0302 the affectation of 10%–30% of the corporal surface prevailed (ACS). In patients with DRb1* 1401/DRQb1* 0503, involvement of <10% of the ACS prevailed. Antécédents: Le terme Pemphigus désigne un groupe de dermatoses autoimmunes chroniques, dont la plus fréquente est le Pemphigus vulgaire (PV). Le lien entre le pemphigus et les sérotypes des antigènes HLA indique qu'il existe une prédisposition génétique à cette maladie. Objectifs: Déterminer la fréquence des antigènes HLA de classe I et II ainsi que les allèles des antigènes HLA de classe II, DR et DQ, chez les patients atteints de PV et en évaluer le risque relatif. Méthodes: Une étude par observation, prospective, transverse et contr?lée a été menée entre 1995 et 1999. Quarante sept patients atteints de PV et un groupe de contr?le formé de 199 personnes du même groupe ethnique y ont participé. Les allèles de HLA ontété déterminés par réaction en cha?ne de la polymérase (PCR). Résultats: Aucun lien significatif n'a été décelé entre les allèles HLA A, B ou C et nos patients. Par contre, un lien solide a été établi entre le PV et deux haplotypes distincts des allèles DR et DQ: DRb1* 0402/DQb1* 0302 et DRb1* 1401/DQb1* 0503. Conclusions: Chez les patients présentant le haplotype DRbl* 0402/DQb1* 0302, 10% à 30% de la surface du corps a été affectée. Chez les patients présentant le haplotype DRb1* 1401/DRQb1* 0503, moins de 10% de la surface du corps a été affectée.     

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.     

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。     

Human leucocyte antigen class II associations in chronic idiopathic urticaria

The major histocompatibility complex (MHC) acts as a marker for self during T-cell ontogeny and is associated with the pathogenesis of many autoimmune diseases. Recent investigations have shown about 30% of patients with chronic idiopathic urticaria (CIU) have IgG autoantibodies against the high-affinity IgE receptor, FcepsilonRI, or IgE. A link between MHC class II alleles and CIU has not been reported previously. DNA was extracted from blood of 100 Caucasian patients with CIU, and the MHC class II type determined using the polymerase chain reaction with sequence-specific primers, testing for DRB and DQB1 alleles. The frequency of alleles in CIU patients was compared with that found in 603 controls. Further human leucocyte antigen (HLA) typing on patient subsets, classified by the patients' responses to intradermal injection of autologous serum and their serum-induced histamine release from basophil leucocytes of healthy donors, was undertaken. HLA DRB1*04 (DR4) and its associated allele, DQB1*0302 (DQ8), are raised in CIU patients compared with a control population (P = 2 x 10-5 and P = 2 x 10-4, respectively). HLA DRB1*15 (DR15) and its associated allele, DQB1*06 (DQ6), are significantly less frequently associated with CIU. The HLA DRB1*04 association is particularly strong (corrected P = 3.6 x 10-6) for patients whose serum has in vivo and in vitro histamine-releasing activity. HLA class II typing is consistent with the concept that CIU is a heterogeneous disease, and supports an autoimmune pathogenesis in a subset of patients.     

Multiple basal cell carcinomas: no association with HLA-DRB, HLA-DQAI or HLA-DQBI in Swedish patients

Summary Many diseases with autoimmune features are associated with alleles of the human leucocyte antigen (HLA). However, few if any malignant disorders have reproducibly been shown to be HLA-associated. In three independent studies, using serological tissue typing techniques, an increase of the HLA class II specificity DR1 has been found in patients with multiple basal cell carcinomas. These observations prompted us to determine the frequencies of DRB1, DQA1, and DQB1 alleles by high-resolution genomic tissue-typing methods, including subdivision of the serological DR 1 specificity in the four sequence-defined alleles, DRB1*0101 to DRB1*0104, in 50 unrelated Swedish patients with a history of four or more basal cell carcinomas and 250 healthy controls. The frequency of DR1 was the same in patients and controls (18%). All DR1-positive patients and controls carried the DQA1* 0101 and DQBI*0501 alleles. Six of the nine DR1-positive patients were DRB1*0101-positive. one DRB1*0102 and two carried the DRB1*0103 allele. This distribution of DRB1*01 alleles did not differ from the one found in the controls. We conclude that genetic factors associated with the HLA class II region do not contribute significantly to the aetiology of multiple basal cell carcinomas.     

HLA-DRB1，DQA1，DQB1基因单倍型与华东地区汉族人群白癜风的相关性

目的 探讨HLA-DRB1、DQA1、DQB1基因单倍型与华东地区汉族人群白癜风的相关性。方法 采用聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)方法检测华东地区汉族白癜风患者HLA-DRB1、DQA1、DQB1位点的等位基因,运用遗传学群体与家系资料计算机分析系统3.0筛选并分析单倍型。结果 与正常人对照组比较,HLA-DRB1^*09-DQA1^*03-DQB1^*0303单倍型频率显著增高(Pc=0.02,OR=2.542)。结论 在华东地区汉族人群中,HLA-DRB1^*09-DQA1^*03-DQB1^*0303单倍型可能是白癜风的易感单倍型。     

HLA markers in familial Lichen Sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families,often associated with HLA markers, mainly DQ7. A genetic co‐etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti‐thyroid peroxidase autoantibodies (anti‐TPO), a hallmark of autoimmune thyroid diseases. Patients and Methods: In 3 families affected by LS, we verified their HLA markers, and identified previously undiagnosed cases of LS and autoimmune disorders. 30 individuals were examined with history, skin biopsy, HLA class I and II typing by PCR‐SSP, and measurement of anti‐TPO, free thyroxine and thyroidstimulating hormones (TSH) levels. Results: There were 8 cases of LS, 50 % of them anti‐TPO+. Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected. Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07, DRB4*. The three latter have been previously associated with LS. Conclusion: New cases of LS and autoimmune disorders can be detected in first degree relatives of patients with LS. The presence of anti‐TPO antibodies strongly suggests autoimmune thyroiditis. There is intra‐familial association between the haplotype HLA‐B*15 ‐DRB1*04 ‐DRB4* and anti‐TPO,emphasizing their link with thyroiditis. New familial approaches might help to make clear the pathogenesis of LS and its association with autoimmune diseases.     

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。