Papers by Conleth Feighery
Journal of Neurology, Neurosurgery, and Psychiatry, Oct 1, 1985
BMC Genomics, Aug 8, 2008
PubMed, Sep 1, 1999
Objective: To examine the gastrointestinal (GI) immune system in rheumatoid arthritis (RA) for ev... more Objective: To examine the gastrointestinal (GI) immune system in rheumatoid arthritis (RA) for evidence of activation. Methods: Duodenal biopsies from 25 patients with RA were obtained by endoscopy. Single cell suspensions from the epithelial layer and lamina propria were prepared. Flow cytometry was used to examine the expression of CD4, CD8, T cell receptor-gammadelta (TCR-gammadelta), TCR-alphabeta, HLA-DR, CD44, and interleukin 2 receptor on gut T lymphocytes. Fifteen disease control (DC) individuals and 6 patients with osteoarthritis (OA) taking longterm nonsteroidal antiinflammatory drug (NSAID) therapy were also investigated. Peripheral blood T lymphocytes from all individuals were examined for the expression of these surface molecules. Results: HLA-DR expression was significantly increased on intraepithelial lymphocytes (IEL) and enterocytes from patients with RA (n = 13) compared with the 2 control groups (p<0.01). Immunohistochemistry also revealed increased expression of HLA-DR on enterocytes from patients with RA. RA IEL (n = 6) expressed significantly higher levels of CD44 (p<0.02). In the lamina propria, a small but significant gammadelta T lymphocyte population (mean 5.5%, range 2-12%) was detected in rheumatoid factor positive RA patients (n = 8) compared with RF negative RA patients (n = 8, mean 2%, range 0.4-6%; p<0.01) and the disease control group (n = 15, mean 2%, range 0.5-5%; p<0.01). None of these changes were detectable in peripheral blood lymphocytes from patients with RA. Conclusion: This study demonstrates evidence of activation of specific components of the GI immune system in RA. Peripheral blood T lymphocytes from patients with RA did not show increased expression of activation markers, suggesting that changes in the RA GI tract are not systemic but localized. Moreover, these changes appear to be independent of NSAID therapy.
Case Reports, Nov 23, 2010
Tissue Antigens, Mar 1, 1988
Monoclonal antibodies to monomorphic determinants of the MHC class II region products, HLA‐DR, DP... more Monoclonal antibodies to monomorphic determinants of the MHC class II region products, HLA‐DR, DP and DQ were used to investigate their expression on cells of the normal and coeliac (both treated and untreated) small bowel. HLA‐DR antigens showed a characteristic distribution in the normal small bowel: epithelial cells in the apical portions of the villi stained heavily, and this staining decreased in intensity towards the villous base. The crypt epithelial cells were clearly unstained. Stellate cells within the lamina propria were also HLA‐DR positive. HLA‐DP antigens showed a similar distribution, although the intensity of staining was less than that seen with HLA‐DR. HLA‐DQ antigens were absent from epithelial cells and were confined solely to cells within the lamina propria. In untreated coeliac disease, the intensities of both HLA‐DR and HLA‐DP were increased, and in addition a more extensive distribution of these antigens was observed. In addition to occurring on the surface epithelial cells, DR and DP antigens were now present on crypt epithelial cells. Despite this change in expression of DR and DP antigens, the distribution of HLA‐DQ was essentially unaltered from that of the normal small bowel. The findings in treated coeliac disease were intermediate between those in the normal and untreated coeliac small bowel. The differential expression of class II antigens by normal and diseased small bowel epithelium which has been demonstrated may have implications for interactions of these cells with cells of the immune system.
Journal of Neurology, Neurosurgery, and Psychiatry, Aug 1, 1986
Digestive Diseases and Sciences, 2006
Celiac disease is caused by sensitivity to wheat gluten in genetically susceptible individuals. T... more Celiac disease is caused by sensitivity to wheat gluten in genetically susceptible individuals. The etiological role of the other wheat-related cereals, barley, rye, and oats, is still debated. In order to investigate this issue further, in this study we examined the immune response of celiac mucosal T cell lines to fractions from all four cereals. Cell stimulation was assessed by measuring proliferation (employing (3)H-thymidine incorporation) or cytokine (IL-2, IFN-gamma) production. All five T cell lines demonstrated immunoreactivity to protein fractions from the four related cereals. In some cell lines, reactivity to wheat, barley, and rye was only evident when these cereal fractions had been pretreated with tissue transglutaminase. This study confirms the similar T cell antigenic reactivity of these four related cereals and has implications for their exclusion in the gluten-free diet. However, despite oats stimulation of T cell lines, this cereal does not activate a mucosal lesion in most celiac patients.
European Journal of Gastroenterology & Hepatology, Aug 1, 2001
Enterocyte lactase expression is a useful marker of gluten toxicity. In this study, the technique... more Enterocyte lactase expression is a useful marker of gluten toxicity. In this study, the technique of flow cytometry was evaluated to quantify lactase expression in coeliac disease (CD). Duodenal enterocyte suspensions were obtained from 23 patients with CD, four patients with dermatitis herpetiformis (DH), and 33 control subjects. The percentage of enterocytes that reacted with anti-lactase monoclonal antibody was determined by flow cytometry. In some subjects, organ culture of duodenal biopsies in the presence of various stimuli (including gluten fractions) was performed before enterocyte analysis. This study demonstrated that lactase expression can be readily investigated semi-quantitatively using flow cytometry. Moreover, the level of expression correlated with the extent of mucosal damage in gluten-sensitive individuals. However, in organ culture experiments, lactase expression did not change in the presence of gluten or after marked T-cell activation for 48 h. Measurement of enterocyte lactase expression by flow cytometry is a useful adjunctive test in the diagnosis and monitoring of gluten-sensitive enteropathy. However, lactase expression is not a suitable marker of gluten-induced toxicity in organ culture.
Journal of AOAC International, Jul 1, 2012
Journal of Pediatric Gastroenterology and Nutrition, Oct 1, 2012
Production of autoantibodies to the enzyme tissue transglutaminase (tTG) is a hallmark of coeliac... more Production of autoantibodies to the enzyme tissue transglutaminase (tTG) is a hallmark of coeliac disease (CD). We have previously demonstrated that the immumoglobulin (Ig) A response to tTG in adult CD specifically targets its catalytic core region, containing the active-site triad of amino acids. The aim of the present study was to investigate this phenomenon in paediatric patients with CD, and to elucidate the contribution of each active-site residue to epitopes recognised. The specificity of the IgG anti-tTG response was also investigated and compared with that of the IgA anti-tTG response, in both paediatric and adult patients with CD. Wild-type and novel variants of tTG were generated via site-directed mutagenesis and expressed as glutathione-S-transferase-fusion proteins in Escherichia coli BL-21. The mutagenic variants of tTG had substitutions of 1, 1, or all of the 3 of the catalytic triad amino acids. All of the recombinant tTGs were tested for their antigenicity in IgA and IgG enzyme-linked immunosorbent assays with cohorts of paediatric (n=63) and adult (n=30) CD sera. Substitution of even 1 amino acid in the catalytic triad resulted in a significant reduction of CD IgA and IgG anti-tTG binding, with all of the mutant proteins displaying diminished antigenicity compared with the wild-type protein. The core region of tTG is specifically targeted from early on in disease course by CD patient autoantibodies of both the IgA and IgG class.
Frontiers in Nutrition, 2021
Clinical and experimental immunology, 1987
Immunohistological analysis of the cellular composition of the small intestinal mucosa in a group... more Immunohistological analysis of the cellular composition of the small intestinal mucosa in a group of untreated and treated coeliac patients and non-coeliac control subjects was performed using monoclonal antibodies and an immunoperoxidase technique. A characteristic cellular distribution was observed within the normal mucosa. The intraepithelial and lamina propria compartments were occupied mainly by T suppressor/cytotoxic and T helper/inducer cells respectively. Further subdivision of lamina propria T helper/inducer cells with the Leu 8 antibody revealed that these were of the Leu 3a+ Leu 8- phenotype. Macrophages, defined by the RFD7 antibody, were seen to occupy the same microenvironment as T helper/inducer cells. T cells expressing the T cell activation antigen defined by anti-Ta1 were found with the normal lamina propria, although few cells were identified by the anti-Tac antibody. HLA-Dr antigens were expressed by stellate cells within the lamina propria, and also by the epith...
Journal of Immunological Methods, 1993
A technique for preparing viable, single cell suspensions of the epithelial layer of small intest... more A technique for preparing viable, single cell suspensions of the epithelial layer of small intestinal tissue obtained endoscopically is described. Constant agitation of four biopsies for 60 min in the presence of chelating and reducing agents gave yields of 1.2-6.7 x 106 cells, of which 11-30% were intraepithelial lymphocytes (IEL). Passage through a nylon wool column removed dead cells. This preparation was suitable for flow cytometric analysis. Using this technique, surface MHC class II molecule expression was studied in 14 patients with normal small intestinal mucosa. Fluorescence labelling of these cells showed strong HLA-DR expression by epithelial cells (EC), DP was expressed less strongly, while little DQ expression could be detected. This technique demonstrates that small intestinal biopsies taken during routine endoscopy can yield adequate numbers of viable epithelial cells to perform flow cytometric analysis.
Journal of Clinical Pathology, 1997
Clinical and Experimental Immunology, 2008
SUMMARY Sensitive ELISA were devised to examine the specificity of circulating IgM and IgA autoan... more SUMMARY Sensitive ELISA were devised to examine the specificity of circulating IgM and IgA autoantibodies for whole human IgG, Fe and Fab fragments of human IgG. Sera from patients with autoimmune and infectious conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), tuberculosis (TB), infectious mononucleosis (IM) and cystic fibrosis (CF) were studied. Results of the ELISA assays using whole human IgG as antigen revealed that a proportion of patients in each of the groups studied had circulating IgM and IgA rheumatoid factors (RF). Fifteen normal individuals studied were negative. In the latex positive RA group, IgM RF and IgA RF had primarily anti-Fc reactivity (100% and 93% respectively), although 3/15 patients also showed IgM anti-Fab reactivity and one patient had high IgA anti-Fab activity. Patients with SLE and TB who had detectable RF levels also revealed predominantly anti-Fc specificity. In contrast, examination of 25 patients with IM showed posit...
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Papers by Conleth Feighery