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Biomedical subjects

C Feighery

Publications and source records attributed to C Feighery.

At least 109 records · Page 6Linked to original sources
PubMed1989

Defective suppression in the autologous mixed lymphocyte reaction in patients with Crohn's disease.

T helper and suppressor cell control of autologous immunoglobulin production was measured in 14 patients with Crohn's disease (CD) using autologous B cells or monocytes to stimulate regulatory T-cell activity. A pronounced defect in suppressor cell function was observed in the patient group but not in matched controls irrespective of whether B cells or monocytes were used as the stimulus. This defect was observed for IgG, A and M. This defect was seen both in patients with active disease and with inactive CD suggesting the possibility that a primary regulatory defect might exist in this disease. The patient group displayed normal helper cell function.

Adolescent↗
PubMed1989

Autoantibody facilitated cleavage of C1-inhibitor in autoimmune angioedema.

C1-inhibitor (C1-Inh) is an important inhibitor of the inflammatory response and deficiency of this inhibitor, which may be hereditary or acquired, is associated with recurrent episodes of edema. Recently, an autoimmune form of angioedema has been described that is associated with functional deficiency of C1-Inh and an autoantibody that impedes C1-Inh function. In this report we describe the isolation of C1-Inh from the monocytes and plasma of a patient with autoimmune angioedema and demonstrate that the patient's monocytes secrete structurally and functionally normal C1-Inh, but show that this protein circulates in the patient's plasma in an inactive, structurally altered form. Furthermore, using analytic gel electrophoresis techniques it is demonstrated that the patient's autoantibody facilitates cleavage of normal C1-Inh, by its target proteases, to the same species of C1-Inh that is found circulating in the patient's plasma. This autoantibody facilitated cleavage of normal C1-Inh is apparently a consequence of destabilization of protease/inhibitor complexes. These findings contribute to our understanding of protease/C1-Inh interactions and document important observations on pathogenic mechanisms in autoimmune disease.

Angioedema↗
PubMed1989

Direct immunofluorescence testing of skin biopsies--an under-utilised diagnostic aid.

Direct immunofluorescence testing of skin biopsies is a simple inexpensive and relatively non-invasive diagnostic procedure currently widely used in dermatological practice for the investigation and diagnosis of dermatological and immunological disorders. This paper reviews the value and applicability of the procedure in a variety of disease states. The sensitivity and specificity of the test to a spectrum of clinical conditions should encourage its more widespread use in general medical and rheumatology practice.

Biopsy↗
PubMed1989

The subclass profile and complement activating potential of anti-alpha-gliadin antibodies in coeliac disease.

In a randomly selected group of coeliac patients, alpha-gliadin antibodies (AGA) of subclasses IgG1 and IgG3 were significantly elevated (p less than 0.01) in comparison to both normal and disease control groups. This result was, however, influenced by increased total AGA levels in the coeliac patients. AGA subclass profiles of cohorts of coeliac and normal controls matched for total IgG AGA were therefore compared. It was found that IgG3 AGA levels were higher in the coeliac group (p = 0.006) while IgG4 titres were higher in the control group (p = 0.005). Titres of IgG1 and IgG2 AGA did not differ between the two groups. Because of the marked differences between the ability of IgG3 and IgG4 to activate complement, alpha-gliadin-specific complement fixation was measured. Using randomly selected coeliac and normal sera, the patient group activated highly significantly greater quantities of complement than controls (p less than 0.01). Furthermore, when samples matched for total IgG AGA were compared, sera from coeliac patients were again found to activate greater amounts of complement than sera from controls (p = 0.024). Thus AGA in coeliac sera are both structurally and functionally distinguishable from AGA in normal control sera.

Adolescent↗
PubMed1989

The immunohistologic features of synovitis, disease activity and in vitro IgM rheumatoid factor synthesis by blood mononuclear cells in rheumatoid arthritis.

The immunohistologic characteristics of synovial membrane obtained from patients with active rheumatoid arthritis (RA) were correlated with disease activity and spontaneous in vitro synthesis of IgM rheumatoid factor (RF) by peripheral blood mononuclear cells (MNC). Positive correlations were found between the intensity of inflammatory cell infiltration and both disease activity (p = 0.0007) and RF synthesis (p = 0.028). Moreover, the intensity of both T cell and B cell infiltration correlated significantly with disease activity. Within the group studied 3 previously described immunohistologic categories were identified. These categories could not be distinguished by clinical measurements, but did differ with respect to their capacity for spontaneous in vitro IgM RF synthesis by blood MNC. Our study provides evidence that a relationship does exist between the immunohistologic characteristics and disease severity in RA. Furthermore, the concept of distinct histologic categories of RA representing different immunopathogenic mechanisms is supported.

Adult↗
PubMed1989

Rheumatoid factors in cystic fibrosis: associations with disease manifestations and recurrent bacterial infections.

Serum IgM and IgA rheumatoid factor (RF) levels were measured by ELISA in 71 adolescent and adult patients with cystic fibrosis (CF) and 69 control subjects. IgM RF values from 15 (21%) CF patients greater than 2 s.d. of control subjects (P less than 0.001). Elevated IgM RF values were significantly associated with worse spirometric measurements of pulmonary function (P less than 0.01) and with more frequent exacerbations of respiratory tract infection (P less than 0.001). A characteristic episodic arthropathy occurred in 27% of IgM RF positive patients, compared with 4% of IgM RF negative patients (P = 0.015). IgA RF values from 26 (37%) CF patients were elevated (P less than 0.001). Pulmonary function was significantly worse in patients with elevated IgA RF values (P less than 0.001). However, IgA RF was not associated with exacerbations of respiratory tract infection or episodic arthropathy. Both IgM and IgA RF values correlated significantly with their corresponding Ig levels, suggesting that RF synthesis was the result of polyclonal B cell activation. It is concluded that serum IgM RF values in CF are associated with worse lung disease and recurring bacterial antigenic stimulation. IgM RF may contribute to the development of arthropathy in some patients. Induction of IgA RF synthesis and its pathogenic potential may differ from IgM RF.

Adolescent↗
PubMed1988

Analysis of the histologic variation of synovitis in rheumatoid arthritis.

One hundred forty-five synovial biopsy specimens were obtained from 30 procedures performed on the knee joints of 29 patients with rheumatoid arthritis. All patients had clinically active rheumatoid arthritis and none had received slow-acting disease-modifying drugs or intraarticular corticosteroids. Scores were assigned to each biopsy specimen for each of 6 histologic features to quantify variation within each joint. In the majority of knee joint biopsies, there was considerable clustering of scores for all histologic features. Thus, on a scale of 0-10, 82% of the scores for synoviocyte hyperplasia were within 1 point of the median score for a given joint. Similarly, between 69% and 85% of the scores for the remaining features (fibrosis, vessel proliferation, perivascular infiltrates, focal aggregates, and diffuse infiltrates of lymphocytes) were within 1 point of the median values. Multiple biopsies were obtained at arthroscopy in 8 patients. Tissue was selected from areas of apparent maximal and minimal involvement, to enhance the likelihood of regional histologic variation. Of the scores for synoviocyte hyperplasia, 91% were within 1 point of the median values for a given joint, and of the scores for the remaining 5 features, 72-94% fell within 1 point of the median values. In addition, highly significant statistical correlations of the intensity of synovial lining layer hyperplasia, vessel proliferation, mononuclear cell infiltration, fibrosis, and clinical measurements of synovitis were observed.

Arthritis, Rheumatoid↗
PubMed1988

Antibodies to Proteus in rheumatoid arthritis.

Increased levels of Proteus antibodies were found in patients with rheumatoid arthritis and coeliac disease, when compared to normal controls or patients with SLE and sarcoidosis.

Antibodies, Bacterial↗
PubMed1988

Differential expression of HLA-D gene products in the normal and coeliac small bowel.

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.

Celiac Disease↗
PubMed1988

Relationship of clinical and immunological abnormalities in haemophilia A to F VIII therapy and HIV exposure: a longitudinal study.

This study was established to examine the longitudinal consequences of F VIII therapy on immune function in 24 patients with haemophilia A. Antibodies to the human immunodeficiency virus (HIV) were found in 15 of 16 patients with severe haemophilia and in 2 of 8 patients with mild disease. The principal clinical and immunological abnormalities were restricted to the HIV antibody-positive patients: T helper cell lymphopenia (less than 0.55 x 10(9)/l) in 10 patients, persistent glandular lymphadenopathy in 4 patients and depressed response to skin recall antigens in 7 of 9 HIV-positive patients tested. Although no extension of these immunological and clinical abnormalities developed in the 18-month period of monitoring, T helper cell counts and platelet counts were significantly lower in a group of patients with established long duration HIV seropositivity (since 1982/1983) in comparison with the remaining seropositive patients. This suggests that a progressive pathological process is associated with infection by this virus, but the factors which determine the long-term sequelae are still unknown.

Adolescent↗
PubMed1988

Altered gastrointestinal immune response in sarcoidosis.

Because of the possible clinical association between coeliac disease and sarcoidosis, the incidence of humoral sensitivity to dietary proteins was examined in patients with sarcoidosis. Raised concentrations of circulating IgG antibodies to alpha gliadin were found in 41/99 sarcoid patients whereas antibody levels to casein, beta lactoglobulin and ovalbumin were similar to normal controls. Subsequently, a group of 26 sarcoid patients were selected for small intestinal biopsy; 11 had raised and 15 normal alpha gliadin antibody (AGA) levels. One AGA positive patient had villous atrophy consistent with coeliac disease. Intraepithelial lymphocyte (IEL) counts were raised in AGA positive (median 30; 95% confidence limits 22-46) and AGA negative (median 24; 95% confidence limits 19-32) sarcoid patients when compared with a control group (median 13.5; 95% confidence limits 10-18) p less than 0.01. Serum IgG concentrations were raised in 11/52 patients tested but there was no correlation between IgG levels and the presence of IgG antigliadin antibodies. HLA Dr typing was done in 21 of the 26 biopsied patients. The coeliac disease associated antigen Dr3 was present in eight of 21 (38%) which is very similar to the prevalence in unselected blood donors (34%). There was no significant difference in IEL counts between Dr3 positive and Dr3 negative sarcoid patients. These findings suggest that in patients with sarcoidosis, there is an altered gastrointestinal mucosal immune response, accompanied in about 40% of patients by specific sensitisation to wheat protein.

Adolescent↗
PubMed1988

Altered immunological reactivity in alveolar macrophages from patients with sarcoidosis.

Lung macrophages may play an important role in the pathogenesis of pulmonary sarcoidosis. In this study, the ability of pulmonary macrophages and blood monocytes from sarcoidosis patients, normal controls and disease controls to provide the accessory signal necessary for the concanavalin A-induced activation of normal blood T cells was examined. Blood monocytes from all groups supplied a significantly greater accessory signal than lung macrophages. The accessory capacity of lavage macrophages from sarcoidosis patients varied over a wide range and correlations were sought between these values and other parameters of disease activity. Whilst there was no correlation with clinical parameters, accessory function of alveolar macrophages correlated significantly with the percentage of T helper cells in bronchoalveolar lavage (BAL) fluid (p less than 0.05) and, more closely, with the T helper:T suppressor ratio in BAL fluid (p less than 0.01). This interrelationship between macrophage activity and the T cell infiltrate favours the probability that both cell types participate in the sarcoid disease process and raises the possibility that T cells of both helper and suppressor phenotypes contribute to the pathogenesis.

Adult↗
PubMed1988

Studies on the interaction between alpha-gliadin and HLA and T cell receptor molecules in coeliac disease.

Coeliac disease has a known strong linkage with the HLA complex and has also recently been linked to the T cell receptor genes but the mechanism whereby these genes confer susceptibility is not known. This study has examined two possible mechanisms: (i) direct, lectin-like binding of alpha-gliadin (the causative agent of CD) to HLA or TcR molecules and (ii) antigenic cross-reactivity between alpha-gliadin and HLA or TcR molecules. A flow cytometer was used to assess interactions between alpha-gliadin, anti-alpha-gliadin antibodies (raised in both coeliac patients and in rabbits) and EBV-transformed B cell lines from coeliac patients and HLA-matched and mismatched normal controls. The B cell lines were shown to express HLA-DP, -DQ and -DR antigens which are also found on coeliac intestinal epithelial cells. After incubating B cell lines with alpha-gliadin over a wide range of concentrations, no binding of alpha-gliadin to any of the cell lines could be detected with either of the gliadin-specific antibodies. This suggests that HLA molecules do not bind to alpha-gliadin in a lectin-like fashion. In contrast to the B cell lines, alpha-gliadin binding to peripheral blood monocytes could be demonstrated. This binding occurred equally to patient and control monocytes and was not influenced by HLA allotype. The second possibility tested was that alpha-gliadin and the disease-associated HLA molecule bear antigenic similarities. However, neither rabbit anti-gliadin serum nor purified human alpha-gliadin antibody bound directly to the B cell lines. Using peripheral blood T cells similar results were obtained; no binding of alpha-gliadin or antibodies to alpha-gliadin was found. Thus this study shows that the HLA and TcR associations with CD are not explained by the direct binding of alpha-gliadin to these molecules nor by a sharing of antigenic determinants between alpha-gliadin and these molecules.

B-Lymphocytes↗
PubMed1987

Removal of endogenous peroxidase activity from cryostat sections for immunoperoxidase visualisation of monoclonal antibodies.

The interpretation of immunoperoxidase staining of frozen tissue sections can be severely limited by the presence of endogenous peroxidase enzymes in the tissue. Previously recommended methods of reducing this enzyme activity were examined, but were found to be unsatisfactory when applied to the small intestine. A method, which effectively eliminates this background staining but which does not interfere with the binding of monoclonal antibodies to various tissue components, is described. This method may prove useful in immunoperoxidase studies of other tissues in which high levels of endogenous peroxidase are present.

Antibodies, Monoclonal↗
PubMed1987

Impaired neutrophil function during anesthesia and surgery is due to serum factors.

Neutrophil function was assessed in patients undergoing anesthesia and surgery using a chemiluminescence (CL) assay. With the anesthetic agents enflurane and nitrous oxide, peroperative CL (99.1 mV; 13.8 SEM: postinduction but prior to surgery) was significantly lower than the preoperative value (146.5 mV; 14.1 SEM) with a mean fall of 30% (P less than 0.001). CL measurements taken 24 hr postoperatively were significantly increased (193.9 mV; 16.4 SEM) over the pre- and peroperative values, showing mean increases of 32 and 96%, respectively (P less than 0.001 in both cases). The inhibitory influence on CL appeared to be due to serum factors since peroperative patients' sera inhibited control neutrophils. Significantly depressed levels of the complement component C3 and IgG detected during the peroperative period (P less than 0.05) may explain this phenomenon. Postoperatively, C3 and IgG levels returned to normal. The transient decrease in peroperative neutrophil function may be a contributory factor to the establishment of postoperative sepsis in surgical patients.

Anesthesia, Inhalation↗
PubMed1987

Characterization and quantification of solubilised HLA-DR antigens from circulating human monocytes using an immunoblotting procedure.

An immunoblotting technique was modified to detect and biochemically characterize HLA-DR antigens expressed on circulating human monocytes. Membrane proteins of peripheral blood monocytes were solubilised using the mildly anionic detergent, sodium deoxycholate. These solubilised proteins were resolved by SDS-PAGE and transferred electrophoretically to nitrocellulose. The HLA-DR antigen was detected using a polyclonal antiserum and two monoclonal anti-HLA-DR antibodies. Both immunoperoxidase and 125I autoradiography techniques were used for visualisation of the antigen. The resolution of HLA-DR reactive material was increased when proteins were renatured with 4M urea after blotting. Immunoprobing of a sample of solubilized membrane proteins showed three bands of HLA-DR antigenic reactivity at molecular weights 65kDa, 55kDa and 46kDa. After storage at -70 degrees C for 2 months, only the 46kDa HLA-DR antigen band was detectable. Nonetheless, the 2-chain HLA-DR molecule was found to be an extremely stable complex which could not be dissociated by boiling in sample buffer containing 5% 2-mercaptoethanol and 2% SDS. A stronger reducing agent, 25 mM dithiothreitol, was required to split the HLA-DR molecule into its alpha and beta subunit chains. Finally, in a study of circulating monocytes from normal subjects, the immunoblotting technique was shown to quantitate solubilised HLA-DR antigen in a reproducible manner.

Electrophoresis, Polyacrylamide Gel↗