Comparisons of clinical features of HLA‐DRB1*07 positive and negative vitiligo patients in Chinese Han population

Background Human leucocyte antigen (HLA)‐II alleles have been found to be associated with vitiligo in different populations, and several studies also suggested that HLA class II alleles/haplotypes were associated with a different type vitiligo. Of HLA class II alleles, DRB1*07 has consistently shown a positive association with vitiligo in Chinese Han population. Objective To further explore the relationship between DRB1*07 and vitiligo and to evaluate the DRB1*07 effect on the clinical features of vitiligo in Chinese Han population. Methods This study investigated DRB1*07 allele distribution in 1178 unrelated Chinese vitiligo patients and 1743 healthy controls using polymerase chain reaction/sequence specific primer method and observed clinical differences between DRB1*07 positive and DRB1*07 negative patients. Results The analysis of the 1178 cases and 1743 controls revealed a highly association between DRB1*07 allele and vitiligo [odds ratio (OR) = 1.97, P = 2.13 × 10^?17]. DRB1*07 positive patients had early disease onset (OR = 1.49, P = 0.001), higher frequency of family history (OR = 1.44, P = 0.006) compared with DRB1*07 negative patients. Conclusions The DRB1*07 showed significant association with vitiligo in the study population. This study confirmed that DRB1*07 positive patients had some obvious clinical differences from DRB1*07 negative patients in the Chinese Han population.     

Correlation between HLA and pityriasis rosea susceptibility in Brazilian blacks

Objectives The human leucocyte antigen (HLA) has been related to susceptibility factors in several diseases. This study aimed to determine the potential genetic susceptibility of patients with pityriasis rosea (PR) through HLA molecular typing analysis. Methods The method of choice was polymerase chain reaction with sequence‐specific primers (PCR‐SSP) using low‐resolution typing kits, with determination of the alleles class I (HLA‐A, HLA‐B and HLA‐C) and class II (HLA‐DRB1, DRB3, DRB4, DRB5 and DQB1) performed in 30 Afro‐Brazilian PR‐diagnosed patients and 45 healthy individuals as the control group (PR‐C). Results Analysis of the HLA typing results showed that the relative risk (RR) of 4.00 [95% confidence interval (95% CI) 1.20–13.28, two‐tailed P = 0.018] for allele HLA‐DQB1*04 class II, detected in 33.3% of PR patients, was significant. By contrast, in the control group only 11.1% of subjects had that allele. Three out of six B*51 alleles and three out of six B*53 alleles detected in PR patients were found, together with the allele DQB1*04. Conclusion We suggest that alleles DQB1*04 may be involved in the genetic susceptibility of PR based on the significant predominance of those alleles observed in the black PR patients. We also recommend that more studies are conducted on populations of other ethnic origins, preferentially with higher resolution techniques of DNA typing.     

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.     

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.     

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.     

蒙古族寻常性银屑病与HLA-Cw及DRB1位点相关性研究

【摘要】 目的 探讨蒙古族人群寻常性银屑病与HLA-Cw 及DRB1等位基因的相关性,为银屑病病因学研究提供依据。方法 序列特异性引物聚合酶链反应（PCR-SSP）对蒙古族寻常性银屑病患者81例及正常蒙古族100例进行HLA-Cw及DRB1位点的等位基因进行分型。结果 银屑病组HLA- Cw*06,DRB1*07等位基因频率显著高于健康对照组,HLA- Cw*04、DRB1*04等位基因频率显著低于健康对照组（Pc ＜ 0.05或0.01）。在发病年龄 ＜ 40岁银屑病及家族史阴性患者中HLA- Cw*06、DRB1*07等位基因频率显著高于健康对照组,而HLA- Cw*04、DRB1*04显著低于健康对照组（Pc ＜ 0.05）。在发病年龄≥ 40岁的银屑病及家族史阳性患者中只有HLA- Cw*06等位基因频率显著高于健康对照组（Pc ＜ 0.05）。结论 HLA- Cw*06、DRB1*07等位基因可能是内蒙古地区蒙古族人群寻常性银屑病的易感基因。HLA- Cw*04、DRB1*04等位基因可能是内蒙古地区蒙古族人群寻常性银屑病发病的保护因子。HLA- DRB1*07可能是发病年龄 ＜ 40岁的银屑病的易感基因,而HLA- Cw*04、DRB1*04则可能是发病年龄 ＜ 40岁银屑病的保护因子。     

Association between HLA-DRB1 polymorphisms and pemphigus vulgaris: a meta-analysis

Background Several studies have reported that HLA‐DRB1 may be correlated with pemphigus vulgaris (PV), but most have been based on small samples and the results remain inconsistent and unclear. Objectives To investigate the correlation between DRB1 and PV by a meta‐analysis of case–control/nonfamily studies. Methods PubMed, Wiley Online Library, ScienceDirect, Google Scholar, Cochrane Library, Chinese National Knowledge Infrastructure and Wanfang databases were searched for studies including: (i) ‘pemphigus’; and (ii) ‘human leukocyte antigen’, ‘HLA’, ‘major histocompatibility complex’, ‘MHC’ or ‘DRB1’. Eighteen selected studies were used in meta‐analyses to evaluate DRB1 alleles and phenotypes by calculating the respective odds ratios (ORs) and 95% confidence intervals (CIs). Stratified meta‐analyses and meta‐regression analysis were also conducted. Results The frequencies of three genotypes (allele and phenotype, respectively) were significantly increased in PV: DRB1*04 [P‐value for comparability (Pc) < 0·00001, OR 3·61, 95% CI 2·28–5·71; Pc = 0·0002, OR 4·14, 95% CI 1·98–8·65], DRB1*08 (Pc = 0·03, OR 2·25, 95% CI 1·07–4·70; Pc = 0·0003, OR 2·46, 95% CI 1·51–4·01) and DRB1*14 (Pc < 0·00001, OR 6·47, 95% CI 4·52–9·26; Pc < 0·00001, OR 9·68, 95% CI 4·47–20·98). Three others (allele and phenotype, respectively) were significantly decreased in PV: DRB1*03 (Pc < 0·00001, OR 0·28, 95% CI 0·19–0·41; Pc = 0·0001, OR 0·25, 95% CI 0·12–0·51), DRB1*07 (Pc = 0·004, OR 0·45, 95% CI 0·26–0·78; Pc = 0·0002, OR 0·27, 95% CI 0·14–0·54) and DRB1*15 (Pc = 0·001, OR 0·35, 95% CI 0·18–0·66; Pc = 0·002, OR 0·32, 95% CI 0·16–0·65). Ethnicity partially explained the heterogeneity of DRB1*07, DRB1*08 and DRB1*14 phenotypes. Conclusions Our findings suggest that DRB1*04, DRB1*08 and DRB1*14 are statistically significant susceptibility factors for PV. Conversely, DRB1*03, DRB1*07 and DRB1*15 may be negatively associated with PV. Specific HLA‐DRB1 types may influence the susceptibility or resistance to PV, which needs further investigations.     

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.     

Human leukocyte antigen (HLA) and single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)-alpha -238 and -308 as genetic markers of susceptibility to psoriasis and severity of the disease in a long-term follow-up Brazilian study

Background The strongest genetic marker for psoriasis is Cw*06. Polymorphisms in the tumor necrosis factor (TNF)‐alpha promoter region, especially replacement of guanine with adenine in positions ‐238 and ‐308 are related to higher TNF‐alpha production and higher risk for psoriasis in Caucasoid populations, not found in Asians. We performed a case‐control study of 69 patients with psoriasis type I and 70 controls, characterized clinical progression along 10‐years of follow‐up in mild or severe disease and determined HLA class I, II, and TNF single nucleotide polymorphisms (SNPs) ‐238 and ‐308 polymorphisms to demonstrate whether these polymorphisms may be genetic risk for susceptibility to psoriasis or severity of the disease in Brazilians. Methods Polymorphisms were identified using PCR/SSP. Alleles, genotypes, and haplotypes frequencies were compared using Fisher’s test. Results More severe disease was found in male patients. It may be suggested that alleles B*37, Cw*06, Cw*12, and DRB1*07 were associated with severe disease course, while B*57 with mild disease. No statistical difference was found between the patients and controls regarding polymorphisms frequencies in TNF SNPs. This study pointed to a higher TNF‐238 G/G genotype frequency (OR: 3.21; CI: 1.06–9.71; P = 0.04) in the group with severe disease. Conclusions Polymorphisms in the TNF‐alpha SNPs do not seem to be a more important genetic risk factor for psoriasis than the already known Cw*06 in Brazilian patients, but these markers may be related to clinical manifestations.     

Investigation of the HLA-DRB1 locus in alopecia areata

To further evaluate the nature of the HLA association with alopecia areata (AA), we investigated the HLA-DRB1 locus in 161 AA patients and 165 matched controls from Belgium and Germany. HLA-DRB1 typing was performed using a recently established method that employs a combination of PCR-SSP (sequence specific priming) and Pyrosequencing(TM) technology. No significant differences were observed for HLA allele groups DRB1 *01, *07, *08, *09, *10, *11, *13, *14, *15, and *16. HLA-DRB1*03 was found to confer a protective effect (7.5% versus 13.6%, p = 0.011). Additional genotyping at the allelic level revealed a significant difference in HLA-DRB1*0301 between patients and controls (6.8% versus 11.2%, p = 0.048). The DRB1*04 allele group was confirmed as a risk factor for the development of AA (20.8% versus 13.3%, p = 0.012), with the allele DRB1*0401 accounting for the greatest proportion of the effect (13.4% versus 7.3%, p = 0.014). Results obtained after subgrouping of the patients according to age at onset, severity and family history of the disease suggests that the genetic effects of the HLA system are strongest in familial cases of the disease.     

The high rate of familial lichen sclerosus suggests a genetic contribution: an observational cohort study

Background Familial lichen sclerosus (LS) has been described in only 37 families. We feel that the association is under‐reported. Objectives To determine the percentage of patients with LS who have a positive family history. Method A large observational‐cohort study of a total of 1052 females at vulval clinics within a University Hospital with a diagnosis of LS of the vulva (clinical diagnosis was confirmed in 80% of cases by histology). Patients were questioned as to family history of LS or balanitis xerotica obliterans; male circumcision for medical reasons; vulval cancer; and routine medical and family history. The outcome was the presence or absence of personal or family history of LS, autoimmune disorder or vulval cancer. Results In total 1052 patients were investigated. Of these, 126 (12%) had a positive family history of LS. These patients belonged to 95 families. Vulval cancer was significantly increased in those with a family history of LS compared with those without (4.1% vs. 1.2%, P < 0.05). There was more associated autoimmune disease in familial LS than in sporadic LS, although this was not statistically significant. (7% vs. 5%, P > 0.2). Conclusion Our data from a large cohort of patients with LS provide evidence of an increased risk for family members to develop LS. This indicates a likely genetic component in the aetiology of LS.     

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.     

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.     

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.     

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.     

Lichen sclerosus premenarche: autoimmunity and immunogenetics

Lichen sclerosus is among the most frequently seen paediatric vulval disorders. In adults a strong association between lichen sclerosus and autoimmune diseases, and also with HLA class II locus DQ7, has been well demonstrated in women and a weaker association in men. These associations have not previously been studied in children, although in other autoimmune diseases, the HLA associations have been strongest in children. We performed HLA tissue typing and looked for autoimmune associations in a group of 30 children with vulval lichen sclerosus. HLA DQ7 was present in 66% of female children with lichen sclerosus compared with 31% in controls. Previous studies reported DQ7 in 51% of adult female patients and 45% of male patients. Sixteen per cent of the children were homozygous for DQ7 as opposed to 5% of controls. In the childhood group, only 4% had another autoimmune disease, but 56% of their parents or grandparents did. Age differences make comparison difficult, but the family history of autoimmunity appears to be strong in the early-onset group, in addition to the stronger association with DQ7.     

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.     

Epidemiology of vitiligo,associated autoimmune diseases and audiological abnormalities: Ankara study of 80 patients in Turkey

Background Recent clinical studies suggest that the pathogenetic mechanisms of vitiligo could be of systemic origin as vitiligo is associated with auditory abnormalities as well as other autoimmune disorders. Objectives To investigate clinical, genetic characteristics and laboratory findings of vitiligo as well as auditory abnormalities and the association of the disease with the other autoimmune disorders. Materials and methods From January to December 2008, we collected‐data from 80 vitiligo patients to establish the clinical and epidemiological profile of vitiligo in Turkey. Results Thirty patients were men and 50 were women, with a mean age of 37 years and a mean onset age of 10 years. Vitiligo vulgaris was the most common type, followed by focal, acrofacial, segmental and universal types. Forty‐four (55%) patients had an associated autoimmune disease. These associated diseases were Hashimoto thyroiditis in 25, alopecia areata in 10, pernicious anaemia in seven and diabetes mellitus in two patients. Statistically significant changes in human leukocyte antigen in patients with vitiligo were HLA A24,‐30, B63, CW6, DR15, DR51, DQ5,‐6. Auditory problems were observed in 37.7% patients. Nine of the 20 patients showed unilateral minimal hearing loss (>30 dB), while the other 11 demonstrated bilateral hearing loss (>30 dB) over a large range of frequencies (2000–8000 Hz). Conclusion Our study demonstrates that vitiligo is a part of systemic autoimmune process. Audiological examination should be performed in all patients for auditory problems which are commonly presented as hypoacusis.     

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 of HLA class I and class II alleles with bullous pemphigoid in Chinese Hans

Background

Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases. Associations of genes, especially human leukocyte antigen (HLA)-DQ alleles, with BP indicate that genetic predisposition contributes to the disease.