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R J Lock

Publications and source records attributed to R J Lock.

At least 37 records · Page 2Linked to original sources
PubMed2001

Antibodies to extractable nuclear antigens. Has technological drift affected clinical interpretation?

Precipitating antibodies to extractable nuclear antigens are important in the diagnosis of connective tissue diseases. Disease associations are defined using gel based techniques. Alternative technologies have been introduced, including passive haemagglutination, enzyme linked immunosorbent assay, and western blotting. This leader contains a review of the literature on the clinical usefulness of these assays, together with knowledge gained from personal experience. Using the example of systemic lupus erythematosus, the sensitivity, specificity, and positive predictive value of the assays for disease is discussed, as is their differences in performance. The conclusion drawn is that disease specificity is method dependent. Validation and audit of performance of the method selected by the investigation laboratory is essential.

Antibodies, Antinuclear↗
PubMed2001

The high prevalence of autoantibodies to tissue transglutaminase in first-degree relatives of patients with type 1 diabetes is not associated with islet autoimmunity.

OBJECTIVE: To determine the extent of celiac autoimmunity in type 1 diabetic patients and the overlap between islet and celiac autoimmunity in their nondiabetic relatives. RESEARCH DESIGN AND METHODS: IgA antibodies to tissue transglutaminase were determined in serum taken from 433 type 1 diabetic patients and 1,442 nondiabetic first-degree relatives. Samples with transglutaminase antibodies above the 97.5th percentile of 347 schoolchildren were also assayed for IgA anti-endomysial antibodies (EMAs). Markers of islet autoimmunity (islet cell antibodies and autoantibodies to insulin, glutamate decarboxylase. and protein tyrosine phosphatase IA-2) had previously been measured in all relatives. RESULTS: In the absence of known celiac disease, the prevalence of transglutaminase antibody levels above the 97.5th percentile of the schoolchildren was 13.4% in diabetic patients and 7.0% in nondiabetic relatives. ENMAs were found in addition to transglutaminase antibodies in 2.6% of probands and in 1.9% of first-degree relatives, but none of the schoolchildren. Transglutaminase antibodies were found to persist in 10 of 30 patients and in 30 of 59 relatives with follow-up samples taken at least 2 years after the initial sample. Of 186 nondiabetic relatives with islet autoantibodies, only 10 also had transglutaminase antibodies. CONCLUSIONS: We found a high prevalence of celiac autoimmunity in patients and first-degree relatives of children with type 1 diabetes, but we found limited overlap between islet and celiac autoimmunity in nondiabetic relatives. The high prevalence of celiac autoimmunity may be explained by shared genetic susceptibility and identifies a population within which screening for the disease may be justified.

Adolescent↗
PubMed2001

Coeliac disease, anaemia and pregnancy.

We have investigated the prevalence of positive serology for coeliac disease in pregnant women, using the IgA anti-endomysium antibody test. Five of 216 pregnant women with a haemoglobin less than 11 g/dl were positive, compared to 0/350 with haemoglobin > or = 11 g/dl. Four of these five had low plasma ferritin levels, indicative of iron deficiency anaemia; the fifth was borderline normal. We found no association between positive coeliac disease serology and folate deficiency. None of thirty mothers of children born with neural tube defects were IgA anti-endomysium antibody positive. This study has identified a very high prevalence of occult coeliac disease in pregnancy and a strong association with anaemia. We advise that in cases with a haemoglobin of less than 11 g/dl in pregnancy, coeliac disease should be excluded.

Adolescent↗
PubMed2000

Changes in the proportions of peripheral blood lymphocytes in patients with worn implants.

We compared the peripheral blood and periprosthetic tissues of 53 patients at revision arthroplasty with those of 30 patients at primary arthroplasty to determine whether there is a systemic difference in lymphocytes in patients with worn hip implants. The absolute number and relative proportion of lymphocytes bearing CD2, CD3, CD4, CD8, CD16, CD19, HLA-DR, kappa and lambda antigens were compared with the levels of IL-1beta, IL-6 and PGE2 in the pseudosynovial membrane as well as with a semiquantitative estimate of metal and polyethylene particles, necrosis and chronic inflammation and the total concentration of metals within the periprosthetic tissues. There was a significant increase in the relative proportion of CD2-positive T-cells and CD16-positive natural killer cells in the peripheral blood at revision arthroplasty compared with primary arthroplasty and an increased proportion of CD8-positive T-cells and a decreased ratio of CD4 to CD8 (helper inducer/suppressor cytotoxic cells). Three control patients, who went on to have revision surgery, had values at primary arthroplasty which were similar to those of patients at the time of revision surgery. These differences did not correlate with the local concentration of metal, plastic or cement or inflammatory response or the type of prosthesis. An inverse correlation was noted between the necrosis in the periprosthetic tissue and both the local production of IL-6 and the absolute numbers of T-cells in peripheral blood. We conclude that there may be several cell-mediated systemic immune responses to aseptic loosening, at least one of which may be directly related to events in the periprosthetic tissues. We cannot exclude the possibility that the changes in the proportion of CD8-positive cells reflected a predisposition, rather than a reaction, to loosening of the implant.

Aged↗
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↗
PubMed1995

Clinical significance of the serial measurement of autoantibodies to neutrophil cytoplasm using a standard indirect immunofluorescence test.

Previous reports have suggested a relationship between changes in indirect immunofluorescence antineutrophil cytoplasm autoantibody (ANCA) titres and disease activity in patients with Wegener's granulomatosis (WG). We analyzed retrospectively the data from 37 patients with biopsy-proven WG during a median follow-up period of 34 (range 8-60) months, during which 532 serial ANCA measurements had been made. A fourfold increase in ANCA titre and/or a positive titre following a series of negative results occurred on 82 occasions, only 19 (23%) associated with clinical relapse, 25 (31%) with intercurrent infection, and 32 (38%) when patients were considered clinically well. The sensitivity of a significant increase in ANCA titre associated with clinical relapse was 43%, with a positive predictive accuracy of 23%. The combination of an increased C-reactive protein-plasma viscosity and a significant increase in ANCA titre occurred on 37 occasions, 15 (40%) with relapse and 17 (46%) with infection. The results of this study suggest that patients with WG who have significant increases in ANCA titres should be carefully monitored. Increased immunosuppression based solely on increased ANCA titres is not justified, as if this had been practiced in this study, then a large number of patients who had infective episodes would have received additional immunosuppression from which they may not have benefited.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Clinical relevance of testing for antineutrophil cytoplasm antibodies (ANCA) with a standard indirect immunofluorescence ANCA test in patients with upper or lower respiratory tract symptoms.

BACKGROUND: Reports from specialist nephrological centres have suggested that the antineutrophil cytoplasm antibody (ANCA) test is highly specific and sensitive for patients with Wegener's granulomatosis. To determine the usefulness of the ANCA test in everyday respiratory practice the results of the test were audited in all patients in the south west of England with respiratory symptoms who underwent the test. METHODS: The results of all 335 patients who had presented with upper or lower respiratory tracts symptoms, or both, and were tested for ANCA by the indirect ANCA test in 1990, as recommended in the broadsheet of the British Association of Clinical Pathologists, were audited. Case notes and necropsy reports were available for review in 231 cases (69%), and in the remainder information was obtained by a standard questionnaire. RESULTS: There were 106 positive results, 45 (44%) from patients with Wegener's granulomatosis. The sensitivity and specificity of a positive ANCA test result in this study were 65% and 77% respectively. For a diagnosis of Wegener's granulomatosis the sensitivity and positive predictive accuracy of a positive cytoplasmic ANCA (c-ANCA) test were greater than of a positive perinuclear ANCA (p-ANCA) test. There were 61 positive tests in 266 patients who did not have Wegener's granulomatosis (23%); of these 27 were from patients with infection, 10 with fibrotic lung disease, nine with underlying connective tissue disease, seven with malignancy, and five following pulmonary emboli. Most of these positive ANCA results were p-ANCA (69%) rather than c-ANCA (31%). Serial ANCA requests were made in 15 cases of patients without Wegener's granulomatosis who had an initial positive ANCA test result. In all cases the ANCA tests subsequently became negative. CONCLUSIONS: In this study the sensitivity and specificity of a positive ANCA test result were less than that reported from specialised centres. However, the test was found to be useful in clinical practice, especially c-ANCA, in conjunction with clinical symptoms of respiratory pathology and evidence of renal disease.

Adolescent↗