Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity

BACKGROUND: Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. OBJECTIVES: To analyse serum autoantibody profile and HLA class II alleles in MMP patients and to correlate this with the clinical presentation of disease. METHODS: Well-defined subgroups consisting of 124 patients with MMP were examined for IgG and IgA reactivity with immunoblotting using human epidermal, dermal and placental amnion proteins. The results were further analysed on the basis of detailed clinical (sites of involvement and disease severity) and immunopathological criteria (immunofluorescence study and HLA class II alleles). RESULTS: Immunoblot assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains, 120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly by IgG autoantibodies included: BP230 in 34 (27%), beta4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) beta4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to beta4 integrin had ocular involvement. In most cases of MMP, more severe clinical features were associated with antibody reactivity to multiple basement membrane zone antigens, as well as reactivity to multiple BP180 component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype. In addition, the subset-dependent autoantibody reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04 and DRB1*11. CONCLUSIONS: Our results confirmed that BP180 is a major autoantigen targeted by the sera of patients with MMP. The disease-prevalent HLA class II alleles and humoral autoimmune response against the particular subsets of antigenic epitope(s) within BP180 ectodomain may contribute to the clinicopathological significance and disease severity of MMP.     

HLA-DQB1 alleles in Italian patients with mucous membrane pemphigoid predominantly affecting the oral cavity

BACKGROUND: Mucous membrane pemphigoid (MMP) used to be considered as a single entity but it is now evident that a range of variants exists. Among them, pure ocular cicatricial pemphigoid (OCP) and pure oral pemphigoid (OP) appear to be very different subsets. Previous immunogenetics studies have found increased occurrence of the DQB1*0301 allele mainly in patients with OCP whereas in patients with OP the data are more open to doubt. OBJECTIVES: To analyse HLA predisposition in a group of Italian patients with MMP predominantly affecting the oral cavity. METHODS: We carried out high-resolution typing of HLA-DQB1 alleles in 28 patients with MMP predominantly affecting the oral cavity and in 97 geographically matched, healthy controls. All were Italian caucasians. RESULTS: The frequency of HLA-DQB1*0301 was significantly increased in the MMP patients compared with the controls (96% vs. 48%; corrected P, Pc = 0.001; relative risk, RR = 28.73). A strong association with DQB1*0301 was also evident in patients with OP compared with the controls (95% vs. 48%; Pc = 0.01; RR = 20.21). There was no significant difference in DQB1*0301 frequency between patients with OP and with MMP not restricted to the oral cavity. Patients with MMP were more frequently homozygous for DQB1*0301 than the controls (43% vs. 8%; Pc < 0.001; RR = 8.34). CONCLUSIONS: Our data suggest that Italian patients with MMP lesions predominantly affecting the oral cavity present the same genetic predisposition linked to HLA-DQB1*0301 previously reported mainly in patients with OCP.     

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.     

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.     

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.     

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.     

Human leukocyte antigens class I and class II in patients with pemphigus in southern Turkey

Background Genetic factors that predispose individuals to pemphigus are considered to play important roles in the development of the disease. Furthermore, population studies of patients with pemphigus have clearly shown that the most prevalent alleles differ across ethnic groups. Objectives This controlled study was designed to detect the distribution of human leukocyte antigen (HLA) class I and II alleles in Turkish patients with pemphigus. Methods Sixty patients diagnosed with pemphigus according to clinical findings, histology, immunofluorescence, and enzyme‐linked immunosorbent assay (ELISA) were enrolled in the study. The control group consisted of 60 healthy adult transplant donors. HLA typing was carried out using a polymerase chain reaction (PCR) with sequence‐specific primers (SSP) method. Results The frequencies of HLAs A*11, CW*01, DRB1*04, DRB1*14, DQB1*05, and DPB1*0401 were found to be statistically significantly higher in the disease group than in controls. By contrast, the frequencies of HLAs B*18, B*50, DRB1*11, DQB1*02, DQB1*06, DPB1*0301, and DPB1*1102 were statistically significantly lower in the pemphigus group than in controls. Linkage dysequilibrium analysis showed that DRB1*14/DQB1*05, A*11/DQB1*05, and A*11/DRB1*14 alleles were detected frequently in pemphigus patients, and DRB1*11/DQB1*05, DRB1*14/DQB1*02, B*50/DQB1*02, and B*50/DPB1*0301 alleles appeared frequently in healthy controls. Conclusions The results suggest that DRB1*04, DRB1*14, DQB1*05, and DPB1*0401 class II HLAs and A*11 and CW*01 class I HLAs are associated with pemphigus in southern Turkey. Observed differences in LD patterns between patients and controls suggest that the coexistence of the respective alleles is strongly determinant of predisposition towards (DRB1*14/DQB1*05 and A*11/DQB1*05) or protection against (B*50/DQB1*02) the disease.     

HLA DQB1*0301 allele is involved in the susceptibility to erythema multiforme

Erythema multiforme (EM) is an acute, episodic inflammatory disorder of the skin and mucous membranes of various etiology that could be related to immunologic hypersensitivity response. EM has been previously reported to be associated with serologically defined HLA-DRw53 and DQw3 antigens. In this report, we reevaluate the role of HLA class II alleles in EM manifestations. With use of the polymerase chain reaction, followed by sequence-specific oligonucleotide hybridization, 35 unrelated Caucasian EM patients and 80 randomly selected healthy subjects were studied, and the DRB3, DRB4, DQA1, and DQB1 alleles were analyzed. The comparison of frequencies of these alleles indicates that (i) susceptibility to EM disease is more associated with the HLA-DQ than the HLA-DR subregions and (ii) that the DQB1*0301 is the most frequent allele among EM patients. Sixty-six percent of the patients had the DQB1*0301 allele compared to 31% of the controls (RR = 4.1; p less than 0.001). An even stronger DQB1*0301 association was found in the patient group with herpes-associated EM (76%; RR = 6.5; p less than 0.001). Our data demonstrate a clear association between an HLA-DQB1 allele and susceptibility to EM.     

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.     

Genotyping of HLA-I and HLA-II alleles in Chinese patients with paraneoplastic pemphigus

BACKGROUND: Class I and class II HLA genes are thought to play a role in the immunopathogenesis of bullous dermatoses such as pemphigus vulgaris and pemphigus foliaceus, but we know little about the genetic background of paraneoplastic pemphigus (PNP) in Chinese patients. OBJECTIVES: To identify class I and class II HLA alleles by genotyping in Chinese patients with PNP, and to find out the possible association between HLA alleles and disease susceptibility. METHODS: Nineteen Chinese patients with PNP were enrolled in this study. HLA-A, B, C, DRB1 and DQB1 alleles were typed by polymerase chain reaction and a colour-coded sequence-specific oligonucleotide probes method. RESULTS: The frequencies of HLA-B*4002/B*4004, B*51, B*52, Cw*14, DQB1*0301, DRB1*08 and DRB1*11 were relatively prevalent in Chinese Han patients with PNP in comparison with normal controls. After correction for multiple comparisons, Cw*14 remained statistically significant, and the other alleles were unremarkable in these patients. CONCLUSIONS: The genetic background predisposing to PNP may be different in patients from various races and areas. HLA-Cw*14 may be the predisposing allele to PNP in Chinese patients, which is different from the predisposing allele in French patients with PNP and the alleles predisposing to pemphigus vulgaris and pemphigus foliaceus.     

广东籍汉人HLA-DQA DQB基因与SLE的易感性研究

目的　探讨SLE患者遗传易感性与HLA DQ基因分型的相关性。方法　以广东籍健康者及SLE患者全血为研究标本 ,DNA的提取用快速盐析法 ,HLA DQ基因分型用序列特异性引物 (SSP)法。结果　SLE患者组中DQA1 0 10 1等位基因的检出率明显高于正常组 (RR =3 .12 ,Pc =0 .0 3 6) ,DQA1 0 3 0 2等位基因的检出率则明显低于正常组(RR =0 .0 9,Pc =0 .0 45 ) ;SLE患者组中DQB1 0 3 0 1的检出率明显低于正常组 ,与正常组比较有显著性差异 (P <0 .0 1)。结论　广东籍汉族SLE与HLA DQ的相关性方面 ,DQA1 0 10 1起主导作用 ;广东籍汉族SLE患者中 ,疾病的保护性基因在本研究中表现为DQA1 0 3 0 2、DQB1 0 3 0 1。     

Molecular analysis of HLA DP and DQ genes associated with dermatitis herpetiformis

HLA class II DQ and DP genes from dermatitis herpetiformis patients were amplified and analyzed using molecular probes and compared to those from celiac disease patients and to an HLA and ethnically matched control group. In dermatitis herpetiformis, as in celiac disease, the strongest association of disease was with the DQ subregion alleles DQB1*0201 and DQA1*0501 that are linked to the DRB1*0301 allele. DQB1*0201 determines the DQw2 serologic marker whereas DRB1*0301 determines the DRw17 serologic marker (formerly termed DR3). A DP subregion allele DPB1*0301 was increased and a constellation of DPB1 alleles that included DPB1*0202, *0901, and *1301 was decreased in dermatitis herpetiformis. DPB1*0101, an allele reported to be increased in celiac disease, was not increased in dermatitis herpetiformis. DP beta chains that lack a negatively charged amino acid residue at position 69 of the DP beta chain are significantly over-represented both in dermatitis herpetiformis and celiac disease patients with the DRw17, DQw2 haplotype, compared to healthy controls with that haplotype. These data favor a multigenic model for the contribution of HLA class II D region genes to dermatitis herpetiformis susceptibility. Further, they indicate that a specific DQ molecule, when present in combination with the product of one of several different DPB1 alleles, may contribute to susceptibility to the intestinal lesion, which is common to dermatitis herpetiformis and celiac disease.     

Human leukocyte antigen class II alleles and natural history of HPV 2/27/57-induced common warts

Epidemiological studies have demonstrated an association between HLA-DQB1*03 alleles and the risk of cervical cancer induced by human papillomavirus (HPV). As persistence of HPV infection is required for developing cervical cancer, we wanted to elucidate the role of HLA-class II allele polymorphisms in the persistence of common warts induced by HPV 2, HPV 27 or HPV 57. Therefore, we determined the distribution of HLA-DQA1, -DQB1, and -DRB1 alleles in 71 patients presenting with HPV 2/27/57-induced common warts which had persisted for at least 18 months as well as in 92 individuals who had never suffered from common warts or whose warts had healed in less than 18 months. Among patients with long-lasting warts, the carriership frequencies and allele frequencies of DQA1*0301, DQB1*0301, DRB1*07 and DRB1*09 were higher, and the allele frequencies of DQA1*0501, DQB1*0603, DRB1*01 and DRB1*03 were lower. Statistically significant differences (Bonferroni adjusted Fishers exact test) were found for carriership frequency of DQA1*0301 (46.5 vs 21.7%, P=0.013) and for carriership frequency (18.3 vs 1.1%, P=0.0015) and allele frequency (12 vs 0.5%, P=0.000013) of DQB1*0301. A greater proportion of patients with long-lasting warts than of subjects without persistent warts were homozygous at the DQA1 (14.1 vs 6.5%) and DQB1 (16.9 vs 8.6%) gene loci. These results suggest that the natural history of cutaneous HPV 2/27/57-induced common warts may be modulated by allele polymorphisms at the HLA-DQA1 and HLA-DQB1 gene loci.     

The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis

Many diseases, notably those having a strong autoimmune component, have been shown to have an association with specific human leukocyte antigens (HLA). The molecular basis for this genetic association with disease is the fact that HLA bind and present peptides derived from self and foreign protein antigens to the immune system for recognition and activation of the immune response. Previous studies with heterogeneous groups of alopecia areata (AA) patients have suggested associations with some HLA class I and class II antigens. For this study we selected only patients with long-standing disease and stratified them into two groups by strict definitions of duration and extent of disease: those with patchy AA and those with either alopecia totalis (AT) or alopecia universalis (AU). The patients were tissue typed for HLA class II antigens by biomolecular methods that provided antigen discrimination at an allele level. More than 80% of all of the AA patients typed were positive for the antigen DQB1*03 (DQ3), suggesting that this antigen is a marker for general susceptibility to AA. In addition, two other antigens were found significantly increased in frequency only in the group of AT/AU patients, DRB1*0401 (DR4) and DQB1*0301(DQ7). This strongly suggests that the two clinical types of AA, namely patchy AA versus AT/AU, can be distinguished by a genetically based predisposition to extent of disease.     

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).     

IgA basement membrane zone autoantibodies in bullous pemphigoid detect epidermal antigens of 270–280 kDa, 230 kDa, and 180 kDa molecular weight by immunoblotting

Bullous pemphigoid (BP) is an acquired subepidermal blistering disease characterized by circulating IgG autoantibodies binding to the 230 and 180 kDa hemidesmosomal proteins. Associated basement membrane zone (BMZ) autoantibodies of the IgA class have been reported in few BP patients. The incidence and clinical relevance of these IgA antibodies, as well as their target antigens are unknown. Sera of 26 patients with BP were analysed for circulating IgG- and IgA-anti-BMZ autoantibodies by indirect immunofluorescence on salt-split human skin. All of the patients had circulating IgG autoantibodies and, in addition, nine (35%) also had circulating anti-BMZ IgA antibodies, that bound to the epidermal side of salt-split skin. By immunoblotting, IgA antibodies in seven of nine sera recognized either the 180 kDa, the 230 kDa, or both BP antigens. Moreover, IgA anti-BMZ antibodies in seven sera also detected an epidermal protein of 270-280 kDa. IgA antibodies did not identify specific bands on immunoblots of dermal extracts. There was no clinical difference between BP patients with or without circulating anti-BMZ-IgA.     

Mycosis fungoides: HLA class II associations among Ashkenazi and non-Ashkenazi Jewish patients

BACKGROUND: An immunogenetic mechanism has been suggested to play a role in the pathogenesis of mycosis fungoides (MF). While results of studies on HLA class I associations haveproved inconsistent, two previous studies showed that certain HLA class II alleles were significantly increased among North American caucasian patients with MF: HLA-DRB1*11 and DQB1*03. OBJECTIVES: To investigate the possible HLA class I and class II associations with MF among Jewish patients. METHODS: The patient group comprised 68 Jewish patients with MF: 38 Ashkenazi and 30 non-Ashkenazi. The control group comprised 252 healthy Jewish volunteers: 132 Ashkenazi and 120 non-Ashkenazi. Tissue typing for HLA class I (A and B) was performed using the National Institutes of Health microlymphocytotoxicity technique. DNA-based low-medium resolution analysis for DRB1* and DQB1* alleles was performed using polymerase chain reaction (PCR) amplification with sequence-specific primers. For those alleles found to have significantly increased frequency, high-resolution analysis was done by means of PCR sequence-specific oligotyping. RESULTS: The allele frequency of HLA-DRB1*11 was found to be significantly increased but only among Ashkenazi patients with MF (30% vs. 19% in the controls; P = 0.034). High-resolution analysis for DRB1*11, not previously performed, suggested that its greater frequency is due to the increased number of Ashkenazi MF patients with the DRB1*1104 allele (P corrected = 0.036). Analysed together, DQB1*03 alleles (DQB1*0301-0304) had a significantly greater frequency in MF as a group as compared with controls (47% vs. 33%, P = 0.003). DQB1*0301 was demonstrated to be the specific allele associated with MF in Jewish patients (allele frequency of 36% vs. 23% in controls; P corrected = 0.0068), which was not the case for North American caucasian patients with MF. No greater frequencies of any of the HLA class I A or B antigens were found. CONCLUSIONS: Our findings further demonstrate the 'universality' of MF HLA class II susceptibility alleles, i.e. HLA-DRB1*11 and HLA-DQB1*03, suggesting that HLA polymorphism is likely to be important in the pathogenesis of MF in Jewish patients, as it is in North American caucasian patients. Not previously reported is our finding that HLA-DRB1*1104 is the specific allele more prevalent among patients with MF. Our study also underscores some differences in HLA profiles between non-Jewish and Jewish patients with MF and between Ashkenazi and non-Ashkenazi Jewish patients, indicating the possibility of diverse HLA disease associations in populations with different genetic backgrounds. Our study provides further evidence for the lack of association between HLA class I and MF.     

HLA-DRB1,DQA1等位基因与广西壮族系统性红斑狼疮器官系统损害相关性研究

目的分析HLA-DRB1,DQA1等位基因与广西壮族系统性红斑狼疮(SLE)器官系统损害的相关性。探讨广西壮族SLE从基因到临床表达的发病机制。方法应用聚合酶链式反应-序列特异性引物(PCR-SSP)技术检测128例确诊的SLE患者的HLA-DRB1,DQA1等位基因,并与患者的各种临床指标进行统计学分析。结果蛋白尿与DRB1*15和DRB1*16负相关,与DQA1*0301正相关;血尿素氮增高与DRB1*1401和DQA1*0501负相关;C3降低与DRB1*1401负相关,与DQA1*0101正相关;白细胞减少与DRB1*16负相关;贫血和淋巴细胞减少与DQA1*0102正相关;血小板减少与DQA1*0301负相关;面部红斑与DQA1*0101负相关;关节痛与DQA1*0104正相关。结论多个HLA-DRB1,DQA1等位基因与广西壮族SLE临床表现有相关性。广西壮族SLE遗传背景与其他人种有所不同。     

A child with localized vulval pemphigoid and IgG autoantibodies targeting the C-terminus of collagen XVII/BP180

Localized vulval pemphigoid of childhood (LVPC) has previously been reported in six girls. Clinical features and immunopathological data have suggested it to be a morphological variant of bullous pemphigoid. Epitope targets of the autoantibodies of these patients have not been defined in detail. We describe a 9-year-old girl with possible cicatricial LVPC and circulating IgG antibodies directed against native collagen XVII/BP180, its 120-kDa soluble ectodomain and against the C-terminus of collagen XVII/BP180. No reactivity was detected towards the NC16A domain of collagen XVII/BP180. Linear IgG and C3 deposits were found along the cutaneous basement membrane zone. On 1 mol/L salt-split skin, IgG autoantibodies were shown to bind to the epidermis, and the HLA type II allele DQB1*0301, a marker with significantly increased occurrence in patients with ocular and oral cicatricial pemphigoid, was identified in this patient. Our data suggest that LVPC is a variant of bullous pemphigoid in which direct immunofluorescence microscopy combined with immunoblot analysis can deliver valuable diagnostic information for differential diagnosis. However, differentiation between the scarring and non-scarring course of the disease cannot be made with the present diagnostic markers and therefore careful follow-up of patients with LVPC is required.     

The immunoglobulin A antibody response in clinical subsets of mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid (MMP) is an immunobullous disease. In MMP there is frequently a mixed antibody response with the presence of IgA and/or IgG antibodies directed toward basement membrane zone antigens. The IgG antibody response in MMP has been studied, but the antigens to which the IgA antibodies react have not been studied. OBJECTIVE: To determine the IgA autoantibody reactivity profiles in patients with MMP. METHODS: Patients who had both ocular and oral MMP were compared with patients who had ocular or oral MMP and with patients who had cutaneous linear IgA disease (LABD) by Western immunoblot studies. RESULTS: Five of 15 MMP patients and 1 of 5 LABD patients had IgA antibodies reactive with the 180-kD bullous pemphigoid antigen. Seven of 15 MMP patients had IgA antibodies reactive with the 97-kD LABD antigen. CONCLUSION: Major antigens in IgA MMP are the 180-kD bullous pemphigoid antigen and the 97-kD LABD antigen.