Search PubMed⌕ Search

Biomedical subjects

S Winsey

Publications and source records attributed to S Winsey.

7 recordsLinked to original sources

Rapid effector function of circulating NC16A-specific T cells in individuals with mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid (MMP) is a chronic blistering skin disease frequently associated with circulating autoantibodies directed to a number of antigens including the NC16A region of BP180. NC16A domain-specific T cells have been identified in the blood of individuals with bullous pemphigoid (BP), pemphigoid gestationis and linear IgA disease, but there are no data investigating the potential role for such T cells in the pathogenesis of MMP. OBJECTIVES: To test the hypothesis that NC16A-specific T cells exist in the peripheral blood of individuals with MMP. METHODS: We isolated peripheral blood mononuclear cells from 10 patients with MMP, 17 with BP and 10 healthy controls and examined the immunogenicity of overlapping peptides spanning the NC16A domain using interferon (IFN)-gamma enzyme-linked immunospot assay. RESULTS: Significant IFN-gamma production was observed in response to the NC16A peptides in two of the patients with MMP and two of the patients with BP but in none of the normal controls. These data suggest that in a minority of individuals with MMP, NC16A domain-specific T cells circulate at sufficiently high frequency to be detectable directly ex vivo and to show rapid effector function. CONCLUSIONS: 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.

Autoantigens↗

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.

Case-Control Studies↗

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.

Adolescent↗

In vitro model(s) for the percutaneous delivery of active tissue repair agents.

There is a need to evaluate the permeability of human ulcerated tissue and periulcer tissue in order to assess the possible treatment of such a localized pathological lesion with a topical therapy. In vitro percutaneous absorption studies were undertaken to evaluate an animal model that may mimic this clinical situation. Porcine skin from three anatomical sites, the ear, abdomen, and dorsum; ischaemic skin (porcine and guinea pig); porcine wounds; and human skin (including periulcer and ulcerated tissue) were investigated, utilizing both whole skin and dermal membranes. Dermal membranes were chosen as representative of ulcerated tissue, as there would be no epidermal barrier present, and the thickness of the dermal membrane was not expected to offer any diffusional resistance to topically applied active agents. A range of chemicals with differing physicochemical properties was investigated using a Franz type diffusion cell. For all tissues a permeability coefficient (kp with units of cm h-1) was measured, along with skin thickness and tissue partition coefficient measurements. Under these experimental conditions and for the range of compounds tested, the results suggest that porcine skin, whole skin, and dermal membranes should be considered as good representative in vitro models for the topical delivery of compounds to human skin and ulcerated tissue, respectively.

Administration, Cutaneous↗