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D J Unsworth

Publications and source records attributed to D J Unsworth.

At least 37 records · Page 2Linked to original sources
PubMed2000

Improving the diagnosis of coeliac disease in anaemic women.

The majority of patients with newly diagnosed coeliac disease have iron deficiency anaemia. Occult gluten enteropathy is common. We looked at blood donor volunteers, unable to donate because they were unexpectedly found to be anaemic, to determine the incidence of coeliac disease and whether this diagnosis is routinely considered. In a 4 month period, 110,973 blood donor volunteers were seen and 1% (1197 women and 183 men) were found to be anaemic. Of 483 anaemic samples selected for testing, 32 out of 483 were positive for IgA anti-endomysial antibodies. Microcytic anaemia was found in all but three of the 32 seropositive cases. Twenty-five out of 32 volunteers agreed to have endoscopic small bowel biopsies and 22 out of 25 (88%) had the typical histological appearances of coeliac disease. Twenty-one out of 22 cases were women. In no case prior to our intervention had these women been investigated for the possibility of coeliac disease. By selecting anaemic subjects for screening, there was an improved detection rate (over 6%) compared with non-anaemic volunteers (0%). There were far more anaemic women in the study population (ratio of anaemic women to anaemic men 5.5:1). We show that, especially in anaemic menstruating women, coeliac disease is unrecognized and under-investigated.

Anemia, Iron-Deficiency↗
PubMed1999

Evaluation of a high-throughput second antibody radiobinding assay for measuring IgA antibodies to human tissue transglutaminase.

We describe a novel high-throughput radiobinding assay for IgA antibodies to tissue transglutaminase (TG) which uses second antibody precipitation to isolate immune complexes. Using this assay, 24 of 25 patients with untreated coeliac disease (96%) and nine of 526 healthy blood donors (2%) had TG antibody levels above a threshold defined by the 97.5th centile of 347 schoolchildren. All patients and five of the nine blood donors with transglutaminase antibodies above this threshold were endomysial antibody (EMA) positive. Using this threshold, 410/445 (92%) routine clinical samples were concordant for TG antibodies and EMA, including 72 of 75 with EMA. TG antibodies above the 97.5th centile were found in 32 of 370 EMA negative samples, 15 of whom had anti-gliadin antibodies (AGA), histologically proven coeliac disease or partial villous atrophy. We conclude that this assay achieves a sensitivity and a specificity at least equivalent to those of EMA. It is technically simple and suitable for coeliac disease screening.

Adolescent↗
PubMed1999

Anti-tissue transglutaminase, anti-endomysium and anti-R1-reticulin autoantibodies-the antibody trinity of coeliac disease.

Anti-tissue transglutaminase has been recently described as the predominant autoantigen in coeliac disease. We purified serum anti-tissue transglutaminase antibodies from three patients with coeliac disease by column chromatography and eluted tissue section-bound R1-anti-reticulin antibodies from sections of rat tissue for two of these. Lastly, we generated seven mouse MoAbs to guinea pig tissue transglutaminase. Each preparation was examined for anti-tissue transglutaminase, anti-endomysium, anti-R1 reticulin and anti-gliadin antibodies. Column-purified patient antibodies and 2/7 mouse MoAbs gave characteristic anti-endomysium/anti-R1 reticulin reactivity on rat, monkey and human tissue. All positive sera gave indistinguishable patterns of immunofluorescence on rat liver, kidney and stomach, monkey oesophagus, and human umbilical cord. Anti-R1-reticulin eluted from sections showed anti-tissue transglutaminase reactivity in 2/2 cases, but 0/2 showed anti-gliadin reactivity. In both, tissue section-eluted anti-R1 reticulin gave endomysial staining on monkey oesophagus. None of the mouse monoclonals, or any of the purified patient's anti-tissue transglutaminase or anti-R1-reticulin antibody showed any reactivity with gliadin. These data confirm tissue transglutaminase as the predominant autoantigen in coeliac disease and suggest that both anti-endomysium and anti-R1 reticulin reactivities seen in coeliac disease arise due to an immune response to tissue transglutaminase. Rigorous immunoabsorption was sufficient to abrogate reactivity in the tissue transglutaminase ELISA, but failed to completely absorb anti-endomysium and anti-reticulin activity. The possibility remains that some of the anti-endomysium and anti-reticulin activity was directed against antigens other than tissue transglutaminase.

Adult↗
PubMed1999

Identifying immunoglobulin-A--deficient children and adults does not necessarily help the serologic diagnosis of coeliac disease.

BACKGROUND: Immunoglobulin A deficiency is more common in patients with coeliac disease and also in patients with other gastrointestinal diseases than in normal people. There is a concern, therefore, that routine serum immunoglobulin (Ig) A testing of all cases of suspected coeliac disease may lead to unnecessary biopsy. METHODS: Four hundred eighty-two routine consecutive samples from cases of suspected coeliac disease or malabsorption (109 children) were tested for IgA anti-endomysium and total IgA. Four hundred twenty-four sera samples also had IgG antigliadin checked for high-titre antibody. Archived adult sera from 31 patients with coeliac disease and 52 disease control subjects were included in the study. RESULTS: Seven routine cases with serum IgA less than 15% of the mean normal for age and four cases with undetectable IgA were identified. Four patients, including three of four with clear deficiency, underwent small bowel biopsy, and all four had normal histologic findings and normal intraepithelial lymphocyte counts. Only one of the seven had high-titre IgG antigliadin antibody but that patient had normal histologic findings. One (3%) of 31 adults with established coeliac disease and 1 (2%) of 52 control subjects were IgA deficient. CONCLUSIONS: Of patients with IgA deficiency, only those with both IgA deficiency and high-titre IgG antigliadin antibody should be routinely considered for biopsy.

Adult↗
PubMed1999

IgA anti-tissue transglutaminase as a diagnostic marker of gluten sensitive enteropathy.

AIMS: To compare and contrast the sensitivity, specificity, and positive predictive values of IgA antibodies to guinea pig tissue transglutaminase (ELISA), endomysium, and reticulin (immunofluorescence), and gliadin (ELISA), and IgG antibodies to gliadin and tissue transglutaminase. METHODS: Sera from 27 newly diagnosed patients with coeliac disease, 65 biopsied gastrointestinal disease controls, and 50 consecutive blood donors were tested. All cases were adults. RESULTS: IgA anti-tissue transglutaminase showed a sensitivity of 85% (23/27 coeliac disease cases seropositive), specificity 97% (2/65 controls and one blood donor showing low titre positivity), and a positive predictive value of 92%. High titre anti-tissue transglutaminase was only seen in coeliac disease. Disease controls with mucosal damage unrelated to gluten enteropathy were IgA anti-tissue transglutaminase negative. Sensitivity, specificity, and positive predictive values for IgA anti-endomysial antibody (monkey oesophagus) were 100%, 100%, and 100%, respectively, and for IgA anti-gliadin, 93%, 95%, and 89%, respectively. CONCLUSIONS: Tissue transglutaminase is a major autoantigen in coeliac disease. IgA (but not IgG) anti-tissue transglutaminase, especially when in high titre, is closely associated with coeliac disease, but low titres may not be disease specific. In this small pilot study, the established IgA anti-endomysial assay was the superior test.

Adult↗
PubMed1998

A practical approach to the use of intravenous immunoglobulin in neurological disease.

Intravenous immunoglobulin is now used in a wide range of neurological conditions. However, side effects are relatively common, treatment is expensive and sustained benefit unusual without repeated administration. This article aims to provide clinicians with an overview of the potential benefits and drawbacks of intravenous immunoglobulin in neurological practice and concludes with suggested guidelines for its use in adults.

Adjuvants, Immunologic↗
PubMed1995

Failure of intradermal skin testing with gluten to produce delayed hypersensitivity reactions in patients with dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is characterized by a rash and a gluten-sensitive enteropathy (GSE) indistinguishable from that of coeliac disease. T-cell-mediated mechanisms have been implicated in the pathogenesis of GSE. It seems feasible that intradermal injection of gluten, in patients known to have GSE, could lead to an influx of T cells sensitized to gluten, with subsequent development of a delayed hypersensitivity-type reaction. Six patients with DH and three normal subjects had intradermal injections of 'Frazer's fraction III' (FFIII; the partial peptic tryptic digest of gluten which is known to be antigenic) and phosphate-buffered saline (PBS) as a control. Skin biopsies were taken at PBS and FFIII injection sites at 48 h. In addition, two of the patients with DH had biopsies taken of FFIII injection sites at 6 h. Monoclonal antibodies and the avidin-biotin-peroxidase technique were used to stain for T cells in the skin biopsies. A monoclonal antibody to a neoepitope exposed in the terminal complement complex and an immunofluorescent method were used to detect the presence of terminal complement component in biopsies taken from two of the control subjects and two of the patients. Both patients and control subjects developed a weal and flare within a few minutes of injecting the FFIII, and this persisted for up to 6 h. No skin reaction was present in either the patients or the control subjects at 48 h. No skin reaction was visible at any time following injection of PBS.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1995

DNA polymorphisms of the complement C6 and C7 genes.

The linked C6 and C7 loci are rich in genetic markers, both at the protein and DNA levels. There are now seven common DNA polymorphisms distributed over about 300 kbp of chromosome 5p12-14. We report a new TaqI RFLP for C7 and a method for typing a C7 variant (T368S) hitherto known only from cDNA clones. We have re-investigated the published RFLPs to provide information on their frequency in North European Caucasian (predominantly British and Irish) subjects and have revised some of the published parameters, especially the sizes of polymorphic restriction fragments. Their precise locations within the genes are also reported: the three markers for C6 are in exon 3, intron 3 and adjacent to exon 17 and the four markers for C7 are in introns 15 and 13 and in exons 13 and 9. The gene frequencies of the second commonest allele of all seven markers lie in the range 0.2 to 0.37, except C6 A/B in the Japanese, where the frequencies of both common alleles are about 0.45. We have estimated the gene frequencies for the DNA polymorphisms which correlate with C7 M/N phenotype and for the C6 A/B phenotype and find them to be the same as the phenotypic estimates in Caucasians and in the Japanese respectively. The markers provide the possibility of defining 128 haplotypes, many (28) of which have been observed. Allelic associations in these genes are generally surprisingly weak.

Alleles↗