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Biomedical subjects

A F Swain

Publications and source records attributed to A F Swain.

12 recordsLinked to original sources
PubMed1997

Epidermolysis bullosa acquisita associated with epidermal-binding circulating antibodies.

Epidermolysis bullosa acquisita (EBA) is a rare, immunobullous disease, characterized by circulating and tissue-bound antibodies against type VII collagen (C7) of anchoring fibrils in the cutaneous basement membrane zone. These antibodies localize to the dermal aspect of salt-split skin on indirect and direct immunofluorescence (IMF). We report two patients with clinical features of EBA, in whom circulating IgG antibodies bound to the epidermal aspect of salt-split skin. In both patients direct IMF of salt-split perilesional skin revealed dermal IgG deposits, and direct immunogold immunoelectron microscopy showed antibody deposits in the region of anchoring fibrils. Their serum failed to react with epidermal or dermal extracts on Western immunoblotting. Epidermal-binding antibodies have not been reported previously in association with EBA, and the IMF findings in these cases suggest the development of autoantibodies to additional epidermal-associated antigens. Target antigen heterogeneity has been reported in most other immunobullous diseases, and may be a hitherto unrecognized feature of EBA.

Adult↗
PubMed1985

The effects of topical treatment with steroids or dithranol on epidermal T lymphocytes and dendritic cells in psoriasis.

We describe the effects of treatment with topical steroids or dithranol on T and dendritic cells in the skin of patients with chronic plaque psoriasis. Resolution of lesions by both types of topical treatments was accompanied by a marked decrease in epidermal T cells. In steroid treated lesions there was also a reduction in DR+ dendritic cells to normal numbers during treatment and the rate of disappearance of both cell types correlated with the rate of resolution. However, a significant reduction of dendritic cells was not usually observed until after the T cells had almost disappeared from the epidermis and substantial healing of lesions had taken place. Dendritic cells in steroid-treated uninvolved skin had decreased to a lower level than in normal skin. In contrast, dithranol did not affect dendritic cells, either in lesional or in unaffected psoriatic epidermis. The decrease in dermal T cells observed with both treatments was more marked in steroid-treated lesions and correlated with resolution. However, blood T cells were unaffected by both treatments. The findings provide further support for the role of T cells in the pathogenesis of psoriasis.

Administration, Topical↗
PubMed1985

Epidermal T lymphocytes and dendritic cells in chronic plaque psoriasis: the effects of PUVA treatment.

The numbers and HLA-DR expression of T cell subsets and dendritic cells in chronic psoriatic plaques were compared to previously reported findings in spontaneously resolving guttate lesions, and the effects of PUVA treatment on these cell populations studied. The chronic lesions showed a similar T helper/T suppressor (TH/TS) ratio (0.66 +/- 0.10) to resolving guttate lesions. However, in contrast to the resolving lesions which do not contain activated epidermal TH cells, a substantial proportion of the TH cells in the persistent plaques were DR+. Moreover, these persistent lesions contained markedly increased numbers of DR+ dendritic cells, approximately 20% of which were T6 negative. PUVA-induced resolution of chronic lesions was associated with depletion of epidermal TH and TS cells, and a subsequent reduction in DR+ dendritic cells. In each patient the rate of disappearance of both cell types correlated with the rate of resolution. Furthermore, the epidermal T cell depletion preceded the onset of clinical improvement. In contrast, significant reduction of the dendritic cells was generally not observed until the lesions were largely resolved. Dendritic cells decreased faster in uninvolved than in lesional skin and to a subnormal level. Dermal T cells also decreased during PUVA therapy but this did not show any obvious correlation with resolution of the lesions. Blood T cell levels were not significantly affected by the treatment. These findings support the concept that the initiation and maintenance of the psoriatic process requires activation of TH cells in the epidermis via interaction with antigen presenting cells. Furthermore PUVA treatment may clear psoriasis by interfering with such a mechanism through its effects on T lymphocytes.

Adult↗
PubMed1984

Epidermal T lymphocytes and HLA-DR expression in psoriasis.

Double staining immunofluorescent techniques and monoclonal antibodies were used to study the numbers, distribution, HLA-DR expression and relationship of T-cell subpopulations and dendritic cells in psoriatic skin. In the dermis there was a definite increase in both T helper and T suppressor cells in uninvolved skin of psoriatic patients, and the appearance of clinical lesions was not associated with any detectable change in the numbers of these cells in the dermis. In contrast, eruption of skin lesions was associated with an increase in the numbers of epidermal HLA-DR+ dendritic cells and also with epidermal influx and activation of T helper cells, while resolution of lesions coincided with increased epidermal entry and activation of T suppressor cells. Both the T helper and T suppressor cells were preferentially found adjacent to epidermal dendritic cells. These findings suggest that the clinical activity of psoriasis may be dependent upon the interaction of T helper and suppressor cells with antigen-presenting cells in the epidermis.

Antibodies, Monoclonal↗
PubMed1984

T-cell subpopulations in the blood and skin of patients with psoriasis.

Monoclonal antibodies were used to determine, simultaneously, the proportions of T-cell populations in the peripheral blood and in the skin lesions of fifty-one patients with psoriasis. The results were analysed in relation to the extent, age and clinical type of the skin lesions. In the group of patients with extensive lesions, a significant reduction in the number of total T (TT) and T helper/inducer-cells, (TH), but not in T suppressor/cytotoxic cells (TS) was observed in the peripheral blood. Furthermore, the skin TH/TS ratio was greater in late guttate and in chronic plaque lesions than the corresponding ratio in the blood. These findings suggest that there is an active selective recruitment of TH cells into established psoriatic lesions. In contrast, the TH/TS ratio in early guttate lesions was the same as in the blood, and significantly lower than in the plaque lesions. An additional finding was a decrease of TS, and a corresponding increase of null cells in the blood of patients with chronic plaque psoriasis. These observations provide further evidence for the participation of T cells in the pathogenesis of psoriasis.

Antibodies, Monoclonal↗
PubMed1983

Increased incidence of malignancy in dermatitis herpetiformis.

A retrospective study of 109 patients with dermatitis herpetiformis showed that malignant tumours had developed in seven patients, the expected incidence being 2.93, giving a relative risk of 2.38. In three of the seven patients the malignancy was a lymphoma, giving a relative risk of 100 for this tumour (expected incidence 0.03). In six of the seven patients who developed malignancies small-intestinal biopsy specimens were macroscopically abnormal, giving a relative risk of 4.22 in this group, which is similar to that reported in adult coeliac disease. Patients treated with a gluten-free diet appeared to have a reduced risk of developing malignancy compared with those taking a normal diet (relative risk with gluten-free diet 1.01 and with normal diet 3.09). A small subgroup of eight patients with linear IgA dermatitis herpetiformis were also studied: three developed malignant disease and in one the tumour was a lymphoma.

Dermatitis Herpetiformis↗
PubMed1983

Pharmacokinetic observations on dapsone in dermatitis herpetiformis.

The pharmacokinetics of dapsone (DDS) and monoacetyldapsone (MADDS) following an oral dose of 150 mg DDS were studied in sixteen patients with dermatitis herpetiformis and seven normal subjects. No differences in DDS disposition were observed between the two groups. The maintenance dose of DDS for individual patients was not significantly correlated with jejunal biopsy morphology, DDS or MADDS half-lives, or the area under the plasma concentration-time curves for DDS or MADDS. DDS plasma protein binding was normal in patients and did not apparently determine the concentration of DDS in skin biopsies, for which the skin/plasma DDS concentration ratio was approximately unity. There was no undue representation of acetylator phenotype in the patient group and no correlation between maintenance dose and MADDS/DDS ratio was noted. The determinants of the maintenance DDS dose have not been found. This may relate to pharmacodynamic differences, but alternatively the concentration of oxidative metabolites rather than DDS or MADDS could be responsible for the therapeutic activity in dermatitis herpetiformis.

Adult↗
PubMed1983

Skin biopsies in relatives of patients with dermatitis herpetiformis.

Out of 109 patients with dermatitis herpetiformis (DH) only one was known to have a first-degree relative with the disease. This is in keeping with previous reports that the familial incidence of DH is low. Study of the family in which two siblings were affected showed both to have HLA-B9 whereas a third, unaffected sibling did not have this antigen. This finding supports the view that both genetic and environmental factors are involved in the pathogenesis of DH, 20 first-degree relatives of 10 other patients with DH had skin biopsies examined by immunofluorescence for the presence of IgA, but none proved positive.

Adolescent↗
PubMed1982

Linear IgA disease in adults.

A multi-centre study is described in which thirty-five adult patients with papillary IgA dermatitis herpetiformis (DH) were compared with forty-two patients with linear IgA deposits, of whom thirty-four had homogeneous-linear (HL) and eight had granular-linear (GL) IgA deposits. The three groups were similar with regard to age of onset, presence of circulating immune complexes and auto-antibodies, incidence of spontaneous remission, histology of lesional skin and response to dapsone. There was a female predominance in the HL group in contrast to the male predominance in the other two. It was not possible to diagnose the HL group clinically. Some patients had a rash typical of DH whilst others resembled pemphigoid. In the majority, however, no specific diagnosis could be made with confidence. The GL group clinically resembled the DH group. The incidence of positive potassium iodide patch tests was greater in the DH group than in the other two. An associated enteropathy was found in 24% of patients in the HL group, 30% of patients in the GL group and 85% of patients in the DH group. Fifty-six percent of HL patients had HLA-B8 compared with 50% in the GL group and 88% in the DH group. Patients with linear IgA deposits may not be a uniform group, but until they can be divided into specific subgroups (e.g. by ultrastructural localization of the deposit or by response to a gluten-free diet) we propose that the term adult linear IgA diseases should be used to distinguish these patients from those with papillary IgA deposits.

Adolescent↗
PubMed1981

Anti-gliadin antibodies and small intestinal mucosal damage in dermatitis herpetiformis.

Sera from forty-six patients with dermatitis herpetiformis (DH) were examined for anti-gliadin antibodies (AGA) by the enzyme linked immunosorbent assay (ELISA) test and by a simple new immunofluorescent (IF) test. AGA were present in fifteen out of thirty-two patients taking a normal diet, but in none of the fourteen taking a gluten-free diet (GFD). The presence of circulating AGA was related to the severity of the enteropathy. AGA were present in all ten patients with a flat mucosa and in four of six with a convoluted mucosa, but in only one out of thirty patients with normal morphology of the small intestine. However, in those patients taking a normal diet and with a normal morphology of the intestine there was evidence of gluten sensitivity compared to those taking a GFD, as the intraepithelial lymphocyte count (IELC) was significantly raised in the peri-nuclear and supra-nuclear positions. The study shows that the presence of AGA in the serum is a good indication of the degree of gluten sensitivity as expressed by severe mucosal damage in patients with DH.

Adolescent↗