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.
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.
The purpose of this study is to assess the role of tumour necrosis factor (TNF) polymorphisms in the risk of developing bladder cancer and effect on tumour stage, grade and progression. In all, seven single-nucleotide polymorphisms in TNF were studied in 196 bladder cancer patients and 208 controls using a PCR-SSP genotyping technique. It was seen that there was a significant association of two polymorphisms in TNF with bladder cancer: the TNF þ 488A allele was found in 28.1% of patients compared with 14.9% of controls (P ¼ 0.0012). In addition, TNFÀ859T was found in 26.0% of patients compared with 14.4% of the controls (P ¼ 0.0036). The two loci were in tight linkage disequilibrium, that is, almost all the individuals having TNF þ 488A also had TNFÀ859T. Patients with the TNF þ 488A or TNFÀ859T were more likely to present with a moderately differentiated tumour than those patients without the uncommon allele. In all, 16.7% of patients with TNF þ 488A and 29.9% of patients without TNF þ 488A presented with a G1 tumour (P ¼ 0.015). A total of 14% of patients with TNFÀ859T and 30.5% of patients without TNFÀ859T presented with a G1 tumour (P ¼ 0.0043). There was no significant effect on time to first recurrence, stage progression or grade progression. In conclusion, a significant association between TNF polymorphisms TNF þ 488A and TNFÀ859T and risk of bladder cancer was detected in this study. Both these polymorphisms were associated with grade of tumour at presentation although there was no significant effect on subsequent tumour behaviour.
Overall, these findings are the first to examine the potential role for antigen-specific autoreactive T cells in the pathogenesis of MMP, and confirm that in some individuals the NC16A domain may be an important target antigen.
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.
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