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Biomedical subjects

D J Unsworth

Publications and source records attributed to D J Unsworth.

67 records · Page 4Linked to original sources

IgA in dermatitis-herpetiformis skin is dimeric.

Skin-biopsy specimens from six patients with dermatitis herpetiformis (DH) were examined by means of indirect immunofluorescence with specific rabbit antisera for the presence of in-vivo J chain and secretory component in IgA deposits. The ability of IgA to bind purified secretory component was studied by means of indirect immunofluorescence with antisera to secretory component. Positive J-chain staining associated with IgA deposits was seen in cryostat sections of all seven DH skin-biopsy specimens. In-vivo secretory component was not detected, but on treatment of sections with a solution of purified secretory component, binding of the latter in the region of the IgA deposits was demonstrated in six of the seven DH skin-biopsy specimens. With double fluorochrome staining binding of secretory component was shown to be essentially coextensive with the IgA deposits. These findings suggest that the IgA deposited in DH skin originates from plasma cells in the small intestine.

Binding Sites, Antibody↗

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↗

Studies on reticulin. I: Serological and immunohistological investigations of the occurrence of collagen type III, fibronectin and the non-collagenous glycoprotein of Pras and Glynn in reticulin.

Collagen Type III, fibronectin and a non-collagenous reticulin component (NCRC) are all secretory products of fibroblasts and other mesenchymal cells. Antisera to human collagen III (isolated from the placenta) human plasma fibronectin, and NCRC (from spleen) have been used to examine possible antigenic relationships between these proteins both by serological studies and by comparison of the distribution of the proteins in various tissues using immunofluorescence. For other comparative purposes, the distribution of collagen and of reticulin in the same tissues was also sought using conventional histological methods. Serologically, the 3 antisera showed distinct specificities. However, when used on sections all 3 antisera gave closely similar staining patterns broadly resembling that of histological "reticulin", although minor differences were noted to be characteristic of the distribution of the respective antigens in certain tissues and in cell monolayers. The results support previous suggestions that histological "reticulin" is not a single entity but is a compound fibrous structure containing collagen Type III, fibronectin and at least 1 additional non-collagenous glycoprotein (NCRC).

Cells, Cultured↗

Binding of wheat gliadin in vitro to reticulum in normal and dermatitis herpetiformis skin.

We have demonstrated by indirect immunofluorescence that wheat gliadin binds in vitro to reticulin-like fibrils present in cryostat sections of human skin, and rat liver, kidney and stomach. Gliadin was seen to bind to fibrils throughout the dermis of both normal and dermatitis herpetiformis skin, and this was particularly striking in the dermal papillae. Serum from 2 dermatitis herpetiformis patients who did not have antireticulin antibody gave reticulin staining when retested by immunofluorescence on cryostat sections of rat tissue pretreated with gliadin. Gliadin treated sections may prove useful in screening patients with gluten sensitive enteropathy for anti-gliadin antibody. Binding of gliadin to skin sites in dermatitis herpetiformis patients and subsequent deposition of antigliadin antibody at these sites may be involved in the development of skin lesions.

Animals↗

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↗

New immunofluorescent blood test for gluten sensitivity.

A new test for the detection of antibodies to gliadin in the sera of children who are gluten sensitive is described. This test is based on the observation that wheat protein binds selectively to connective tissue fibres in cryostat sections of mammalian tissues. Sera containing antibodies to gliadin give a reticulin pattern of staining on section pretreated with wheat gliadin if tested by indirect immunofluorescence. Antibodies to gliadin were detected in this manner in sera fom all of 32 children with coeliac disease, in 16 of whom a provisional diagnosis had been given and in 16 an established diagnosis confirmed by gluten challenge. The incidence of reticulin antibodies detected on untreated sections (in the absence of gliadin) was only 28%. Gliadin antibodies were also present in sera from 15% of 152 children with gastroenterological disorders other than coeliac disease, but most of these non-positive results for coeliac disease were in patients with transient gluten in tolerance, cows' milk-sensitive enteropathy, or Crohn's disease. This new test, although not specific for coeliac disease, promises to be of value as an indicator of gluten sensitivity, and when negative excludes a diagnosis of coeliac disease. It may also be useful in monitoring diet, and in determining when rebiopsy after gluten challenge in appropriate.

Adolescent↗

IgA anti-gliadin antibodies in coeliac disease.

Sixty-two sera from children under investigation for gastrointestinal disease were tested for IgA, IgG and IgM antibodies to gliadin by two different methods: an immunofluorescent (IF) test, and a mixed reverse (solid-phase) passive antiglobulin haemadsorption (MRSPAH) test. There was good agreement between the tests. Both tests detected gliadin antibodies of IgG and IgA class in sera from children with active coeliac disease, which tended to disappear when a strict gluten-free diet was instituted. Serum antibodies to gliadin of IgA class were associated with severe small intestinal villous atrophy and were found almost exclusively in coeliac disease. Gliadin antibodies of IgG class were less disease-specific and were occasionally detected in sera from children with gastrointestinal disease other than coeliac disease--notably in sera from children with transient gluten intolerance.

Adolescent↗

Life-threatening acute pulmonary haemorrhage in primary Sjögren's syndrome with cryoglobulinaemia.

We describe a woman with primary Sjögren's syndrome who presented with an acute pulmonary-renal syndrome resulting from cryoglobulinaemic vasculitis. Pulmonary manifestations of Sjögren's syndrome are relatively common, whereas overt pulmonary complications of cryoglobulinaemia are rare. Pulmonary haemorrhage is rare in either disorder. The combination of Sjögren's syndrome, cryoglobulinaemia, and acute pulmonary haemorrhage has not been previously reported.

Acute Disease↗

Anti-reticulin antibodies: useful adjunct to histopathology in diagnosing celiac disease, especially in a developing country.

R-1 anti-reticulin antibodies (ARA) were present in sera of 10 of the 12 children who subsequently fulfilled the ESPGAN diagnostic criteria for celiac disease (CD), but was not found in any children in the age-matched control groups, viz., severely malnourished (n = 20), acute gastroenteritis (n = 23), normally nourished asymptomatic (n = 38), and 42 children with protracted diarrhoea and failure to thrive due to nonceliac causes. ARA was a highly specific (100%) and sensitive (83%) assay for the early diagnosis of CD. A positive ARA assay with an initial subtotal villous atrophy was seen to always suggest CD, and these together would provide a useful basis for instituting gluten-free diets in suspected cases of CD rather than histological findings alone, which may be often present in children in the third world with protracted diarrhoea and associated severe malnutrition.

Autoantibodies↗