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D J Unsworth

Publications and source records attributed to D J Unsworth.

At least 55 records · Page 3Linked to original sources
PubMed1994

Serological screening suggests that adult coeliac disease is underdiagnosed in the UK and increases the incidence by up to 12%.

Because coeliac disease often presents atypically it is underdiagnosed. It is suggested that the detection rate may be increased by 12% if serology is used to identify cases of occult enteropathy. All adults noted incidentally to be R1 anti-reticulin antibody (ARA) positive in the course of routine autoantibody testing of 6532 sera over one year were followed. None of the eight patients with seropositive serum was suspected of having coeliac disease. All eight had high titres of IgA anti-gliadin and IgA anti-endomysial antibodies, neither of which is detected in a routine autoantibody test, in addition to IgA R1-ARA. On clinical review coeliac disease was considered probable in only one patient, but because of the strong serological evidence of gluten sensitivity, jejunal biopsy was advised in all eight. Seven agreed and all had villous atrophy and crypt hyperplasia in keeping with coeliac disease. Six of the seven presented initially with vague symptoms such as tiredness or arthralgia. These symptoms disappeared after several weeks of gluten withdrawal. Forty two sera showing reticulin staining patterns other than R1 were used as controls. Low titre IgA anti-gliadin was noted in two of 42 but none had IgA anti-endomysial antibody. These 42 cases were not recommended for biopsy. During our study 58 other new adult cases of coeliac disease were diagnosed, primarily on clinical rather than serological grounds, at the four hospitals that request autoantibody studies. Occult coeliac disease detected serologically thus increased the overall incidence of coeliac disease by 12% from 58 to 65 cases. R1-ARA, even in the absence of the expected symptoms and signs of coeliac disease, is an indication for jejunal biopsy and is a reliable indicator of occult coeliac disease.

Adolescent↗
PubMed1993

Defective IgG2 response to Pneumovax in HIV seropositive patients.

OBJECTIVE: To determine whether HIV (Human Immunodeficiency Virus) antibody positive adults are capable of mounting an effective immune response when immunized with polyvalent pneumococcal vaccine. DESIGN: 28 patients (nine homosexual men, one bisexual man, three heterosexual females, 10 injecting drug abusers, five haemophiliacs) and 11 healthy volunteers, were immunised with Pneumovax II and titres of IgG1 and IgG2 specific antibody measured before and 1 month after immunisation. Magnitude of immune response was related to CD4 T-lymphocyte count at time of immunisation to establish whether responses are better in early disease. MAIN OUTCOME MEASURES: Based on our data in healthy volunteers we defined an adequate response to Pneumovax II as a post immunisation IgG2 antibody level at least 50% greater than the pre immunisation level. RESULTS: The magnitude of the response was significantly higher in the normal volunteers (U = 95; p = 0.0328). Adequate IgG2 responses were seen in 11/11 normals but in only 14/28 HIV seropositives (chi 2 = 8.58; p < 0.01). Poor responses were unrelated to the CD4 T-lymphocyte count at immunisation. Absolute IgG2 deficiency accounted for the poor response in only 1 HIV patient. CONCLUSION: 50% of HIV antibody seropositive individuals fail to mount adequate immune responses to polyvalent pneumococcal vaccine. Non responders are unlikely to be protected.

Adult↗
PubMed1993

Extracts of wheat gluten activate complement via the alternative pathway.

We studied the ability of wheat gluten and its subfractions to activate complement directly. A sensitive sandwich ELISA employing a monoclonal antibody (MoAb) to a C9 neoepitope exposed in the terminal complement complex (TCC), a functional haemolytic assay for C5b6 generation, and Laurell's electrophoretic method of estimating C3 conversion to C3bi were used. On a weight-for-weight basis, enzyme solubilized Frazer's fraction three of gluten (FIII) produced approximately 75% of the complement activation seen with the potent activator zymosan. By contrast, activation with whole insoluble undigested gluten was very weak and similar to that seen with ovalbumin or beta-lactoglobulin. The results were the same using normal human serum or sera from patients with coeliac disease, dermatitis herpetiformis, or hypogammaglobulinaemia as the complement source. Activation by both zymosan and FIII was blocked in 0.01 M EDTA, but not in 0.01 M EGTA with 0.0025 M magnesium chloride. Zymosan and FIII activated complement in a serum from a patient with an intact alternative pathway but classical pathway haemolytic activity (CH50) of zero. Preferential heat inactivation of the alternative pathway inhibited both zymosan- and FIII-induced activation. Our results confirm that FIII is a strong activator of the alternative pathway. We discuss how gluten enteropathy might be initiated by complement.

Adult↗
PubMed1987

Gliadins bind to reticulin in a lectin-like manner.

It has previously been reported that gliadins bind to reticulin in tissue sections. Three lines of evidence are reported in this study which indicate that the gliadins bind to reticulins because they are lectins which bind to sugars expressed on glycoproteins in reticulin and other sites. First, immunofluorescence studies on tissue sections showed that although gliadin binding is largely confined to areas rich in reticulin, it is, nonetheless, also seen in one or two other sites devoid of reticulin. Second, by using fluorescein-labelled lectins of known specificity, it has been shown that the areas to which gliadins bind in tissue sections (including those sites devoid of reticulin) are rich in particular sugars. Third, it has been shown that one of these sugars, alpha-D-mannose, partially inhibited gliadin binding to tissue sections.

Animals↗
PubMed1987

Evidence for the role of a human intestinal adenovirus in the pathogenesis of coeliac disease.

We previously noted a region of amino acid sequence homology between A-gliadin, a major alpha-gliadin component known to activate coeliac disease, and the early region E1b protein of human adenovirus serotype 12 (Ad12), an adenovirus isolated from the human intestinal tract. In the present study sera from coeliac disease patients from the United Kingdom and the United States were assayed for neutralising antibody to Ad12 as evidence of past exposure to that virus and for antibody to synthetic peptides of A-gliadin from the region of shared sequence with the Ad12 E1b protein. Eighty nine per cent of untreated coeliac disease patients had evidence of previous Ad12 infection. There was also a significant increase in the prevalence of neutralising antibody to Ad12 among treated adults (33.3%) and children (30.8%) with coeliac disease compared with controls (0-12.8%) in the western USA and in London. There was no evidence for an increased prevalence of infection with a closely related adenovirus, adenovirus 18, or another enteric virus, Echovirus 11, among coeliac disease subjects. Additional studies documented that a region of A-gliadin that shares amino acid sequence homology with the adenovirus 12 E1b protein could be recognised as an antigenic determinant in active coeliac disease patients. Taken together, these data are compatible with the hypothesis that a viral protein may play a role in the pathogenesis of coeliac disease, perhaps by virtue of immunological cross reactivity between antigenic determinants shared by the viral protein and alpha-gliadins.

Adenoviridae Infections↗
PubMed1985

Autoimmunity in diarrhoeal disease.

Evidence for autoimmunity in diarrhoeal disease is reviewed. Firstly, coeliac disease (CD) is considered. The incidence of tissue-reactive autoantibodies in both adults and children with CD (68% and 65%, respectively) is higher than the incidence of these autoantibodies in controls (6% in normal adults, and 14% and 9% in disease controls drawn respectively from adult and child populations). The R1 antireticulin antibody, when present, was found to disappear after several weeks on a gluten-free diet, but in contrast, other autoantibodies persisted. Secondly, a case is argued for a new disease category, namely "autoimmune enteropathy." Seven cases are reviewed in which patients presented with protracted diarrhoea, a small intestinal enteropathy which failed to heal during periods of total parenteral nutrition, and evidence of a predisposition to autoimmunity (namely, the presence of high titre autoantibodies including one specific for gut epithelium, and/or the presence of associated diseases regarded to be autoimmune). Thirdly, evidence for autoimmunity in inflammatory bowel disease is reviewed and includes discussion of serum goblet cell antibodies and of circulating T cells which participate in antibody-dependent cellular cytotoxicity in vitro using colonic epithelial cells as targets. Finally, an unusual child is described who presented with chronic diarrhoea and a flat small intestinal mucosa, who responded to gluten withdrawal but who later relapsed spontaneously during a strict gluten-free diet. Her mucosa healed only after a period of total parenteral nutrition and treatment with oral steroids. This child's enteropathy was also associated with thyrotoxicosis and a microscopic colitis.

Adult↗
PubMed1985

Arthritis and coeliac disease.

We report six patients with coeliac disease in whom arthritis was prominent at diagnosis and who improved with dietary therapy. Joint pain preceded diagnosis by up to three years in five patients and 15 years in one patient. Joints most commonly involved were lumbar spine, hips, and knees (four cases). In three cases there were no bowel symptoms. All were seronegative. X-rays were abnormal in two cases. HLA-type A1, B8, DR3 was present in five and B27 in two patients. Circulating immune complexes showed no consistent pattern before or after treatment. Coeliac disease was diagnosed in all patients by jejunal biopsy, and joint symptoms in all responded to a gluten-free diet. Gluten challenge (for up to three weeks) failed to provoke arthritis in three patients tested. In a separate study of 160 treated coeliac patients attending regular follow up no arthritis attributable to coeliac disease and no ankylosing spondylitis was identified, though in a control group of 100 patients with Crohn's disease the expected incidence of seronegative polyarthritis (23%) and ankylosing spondylitis (5%) was found (p less than 0.01). Arthritis appears to be a rare manifestation of coeliac disease. This relationship may provide important clues to the role of gastrointestinal antigens in rheumatic diseases.

Adolescent↗
PubMed1985

Does the reticulin binding property of cereal proteins demonstrable in vitro have pathogenetic significance for coeliac disease?

We used an indirect immunofluorescence technique, using rabbit antisera against cereal protein extracts, to determine which cereal proteins bind to reticulin in tissue sections and which do not. Wheat albumin extracts and globulins and gliadin extracts from a range of different wheat varieties, and prolamine extracts of barley and rye each bound to reticulin in vitro, while prolamine extracts of maize and rice did not. Wheat gluten subfractions were also tested. Subfractions B and C and subfractions B2 and B3 did bind, but fraction A and subfraction B1 did not. The results suggest an association between in vitro reticulin binding and the ability to induce gluten sensitive enteropathy on feeding.

Animals↗
PubMed1985

Studies on the significance of the R1 anti-reticulin antibody associated with gluten sensitivity.

The R1 type anti-reticulin antibody (ARA) is closely associated with gluten-sensitive enteropathy. It disappears from the circulation within a few weeks of starting on a gluten-free diet and often reappears following gluten challenge. It is not clear how gluten ingestion leads to the production of the ARA. We have investigated four possibilities. (1) The ARA is simply a food antibody generated against meats in the diet. (2) The ARA is an anti-gluten antibody which cross-reacts with reticulin. (3) Gluten binds to gut reticulin in vivo rendering reticulin autoimmunogenic. (4) Immune complexes of gluten and anti-gluten antibody bind to reticulin (by virtue of the affinity that gluten has for reticulin) to give the appearance of an ARA in immunofluorescence tests. Our results do not support any of these possible explanations, and the significance of the ARA remains obscure.

Antibodies↗
PubMed1984

Evidence that the IgA in patients with linear IgA disease is qualitatively different from that of patients with dermatitis herpetiformis.

A previous study using immunofluorescent techniques showed J-chain to be present in the uninvolved skin of patients with papillary IgA dermatitis herpetiformis (DH) in a distribution that was coextensive with the IgA. This implied that the IgA was dimeric and of mucosal origin. In this study, fifteen patients with papillary IgA deposits, fifteen with homogeneous-linear (HL) IgA deposits and four patients with granular-linear (GL) IgA deposits were tested for the presence of in vivo bound J-chain. All fifteen patients with papillary IgA deposits and all four with GL IgA deposits had J-chain staining coextensive with the IgA. However, only one of fifteen patients with HL IgA deposits demonstrated in vivo bound J-chain that could not be accounted for by coexisting IgM deposits. These findings indicate that the IgA in patients with HL deposits is qualitatively different from that in patients with papillary and GL IgA deposits and makes the distinction between the two types of linear fluorescence particularly important.

Adult↗
PubMed1984

Failure of R1 type anti-reticulin antibody to react with fibronectin, collagen type III or the non-collagenous reticulin component (NCRC).

The precise specificity of the R1 anti-reticulin antibody (ARA) associated with untreated gluten sensitive enteropathy (GSE) is unknown. Collagen type III, fibronectin and the non-collagenous reticulin component (NCRC) of Pras & Glynn (1973) co-distribute in tissues in a manner consistent with their being components of reticulin. We therefore used purified preparations of these connective tissue components in studies of the specificity of the ARA. Our results show that the ARA found in GSE does not react with collagen type III, fibronectin or NCRC.

Antibodies↗
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↗