PubMed Health⌕ Search

Biomedical subjects

E J Holborow

Publications and source records attributed to E J Holborow.

At least 19 recordsLinked to original sources
PubMed1991

Localization of circulating immune complexes from patients with rheumatoid arthritis in murine spleen germinal centres.

In previous studies we have demonstrated high levels of rheumatoid factor (RF) and large-size (greater than 22S) circulating immune complexes (CIC) in the serum of rheumatoid arthritis (RA) patients with extra-articular disease. These findings were paralleled by a concurrent increase in the level of RF-associated cross-reactive idiotypes (CRI) and an apparent diversification of the RF repertoire detected in the serum of the same patients. In the present study we examine the ability of CICs to activate the complement system in vivo, and its possible influence on expanding the RF repertoire in RA patients with extra-articular disease. Activation of complement by CICs is the key for germinal centre localization and long-term retention of such complexes on the surface of follicular dendritic cells (FDC), and so provides a source for the selection of cells with high affinity receptors for IgG and leads to the establishment of immunological memory. CICs containing different immunoglobulin isotypes and from different patients localized in mouse spleen germinal centres. However, intense localization was mainly seen for IgG-containing complexes from the serum of patients with large-size (greater than 22S) IgG-IgM RF complexes. The ability of these complexes to localize in mouse spleen germinal centres was related to activation of the complement system via the classical pathway in the patients' sera. Localization of IgG complexes was significantly (P less than 0.05) higher in sera from RA patients with extra-articular disease than those with articular disease alone. This study demonstrates the ability of large-size (greater than 22S) IgG-IgM RF complexes to activate complement, and suggests a possible role for such complexes in modulating the immune response to IgG in RA patients with extra-articular disease.

Animals↗
PubMed1991

Characterisation of the size and composition of circulating immune complexes in patients with rheumatoid arthritis.

The size and composition of circulating immune complexes in the sera of patients with rheumatoid arthritis (RA) were studied in relation to different manifestations of the disease. Circulating immune complexes from the sera of 94 patients (50 with extra-articular disease) and 10 matched controls were fractionated by sucrose density gradient ultracentrifugation. The composition, immunoglobulin and rheumatoid factor (RF) concentrations within each of the fractions were determined by a sensitive enzyme linked immunosorbent assay (ELISA). Intermediate size (14S-21S) IgG complexes containing RF activity and 22S IgG-IgM RF complexes were found in the sera of 40 patients with RA, while intermediate size complexes of self associated IgG RF and larger size complexes (greater than 22S) of IgG RF and IgM RF were associated with extra-articular features of RA (50% of extra-articular disease). Complexes containing IgA were found in the sera of many patients with RA, and dimeric IgA RF mainly in patients with extra-articular disease. These results support the view that whereas small size circulating immune complexes are of no primary pathogenic importance in synovitis, large size (greater than 22S) circulating immune complexes may play a role in extra-articular disease in RA. Current understanding of the formation of large complexes provides a biological explanation for their occurrence and effects.

Antigen-Antibody Complex↗
PubMed1989

Autoantibodies to intermediate filaments in sera of patients with Schistosoma mansoni infection.

Autoantibodies to the intermediate filament proteins vimentin and keratin were studied in sera of 50 Caribbean patients with Schistosoma mansoni infection and 50 control subjects. Autoantibodies were detected by indirect immunofluorescence on HEp-2 cells pretreated with colchicine. The incidence of anti-vimentin antibodies in patients' sera was 94% for IgM, 12% for IgG, and 4% for IgA; in the control subjects incidence was 52%, 0%, and 4%, respectively. Anti-keratin antibodies were found in 82%, 4%, and 4% of patients' sera and 42%, 0%, and 2% in controls, respectively. The difference between the geometric means of titres for patients (1:150) and controls (1:26) was highly significant (P less than 0.001). The possible role and genesis of autoantibodies to intermediate filaments is discussed.

Adolescent↗
PubMed1988

T cell cytotoxicity to Epstein-Barr virus infected B cells: comparison of patients with rheumatoid arthritis and their HLA identical siblings.

Specific T cell cytotoxicity to Epstein-Barr virus (EBV) infected B cells is reported to be abnormal in rheumatoid arthritis (RA). The regression phenomenon was used to determine whether the immunoregulatory defect in RA is restricted to T cells, B cells, or HLA type. Peripheral blood T and B cells from patients with RA and their HLA identical healthy siblings were mixed in varying ratios with and without EBV, and thymidine incorporation was measured on days 7, 14, and 21. The results suggest that the T cell abnormality is related to disease activity and that an inherent defect exists in the rheumatoid B cell which is independent of disease activity.

Aged↗
PubMed1987

The effects of adherent cells on measurement of the hyper-responsiveness of rheumatoid B lymphocytes to Epstein-Barr virus.

Rheumatoid peripheral blood mononuclear cells show an increased responsiveness to superinfection with Epstein-Barr virus (EBV). We have investigated the role of adherent cells in this hyperresponsiveness using two different methods of adherent cell depletion. Depletion of adherent cells from both rheumatoid and normal mononuclear cells, using either dextran bead columns or plastic petri dishes, produced inconsistent changes in the response of autologous non-adherent cells to EBV. The addition of supernatants of cultured rheumatoid adherent cells also produced an inconsistent change in response although normal adherent cell supernatants increased the responsiveness of autologous non-adherent cells to EBV. The inconsistencies observed are discussed with respect to adherent cell subpopulations present in rheumatoid and normal peripheral blood mononuclear cell preparations when using recognized methods of adherent cell depletion.

Arthritis, Rheumatoid↗
PubMed1987

IgM, IgG and IgA rheumatoid factors (antiglobulins) in early rheumatoid arthritis and their production of articular index over one year.

An enzyme-linked immunosorbent assay was used to detect antiglobulins (rheumatoid factors, RF) of various classes in 33 patients with recently diagnosed rheumatoid arthritis and to follow their progress with 3-monthly checks for 1 year. For RF, IgA-RF and IgM-RF showed greater sensitivity than the latex test, either or both being positive in 76%. There was no correlation between any of the measures of RF and patient's clinical status as judged by articular index (AI), or serum CRP level. For individual patients, RF levels varied considerably between assessments. The best predictors of clinical status over 1 year were the initial AI and the latex test for RF. While class-specific measurement of RF is more sensitive than the latex test, the variation of individual classes of antiglobulins over time within individual patients makes them less helpful as predictors of disease progress.

Arthritis, Rheumatoid↗
PubMed1986

The specificity of human autoantibodies to IgG: the development of methodology for measuring the specificity of antiglobulin isotypes in rheumatoid and normal sera.

A simple enzyme-linked immunosorbent assay (ELISA) inhibition test was devised to determine the separate specificities for rabbit IgG, Fc, and Fab fragments of IgM, IgG, and IgA antiglobulins in sera obtained from rheumatoid and normal individuals. Results of this test showed that most of the anti-rabbit IgG activity present in the three immunoglobulin (Ig) isotype preparations from a rheumatoid serum was specific for the Fc portion of whole IgG. Some anti-Fab activity was detectable in all three Ig isotypes examined, but this had much less avidity and/or specificity than the anti-Fc activity. In contrast, normal antiglobulins of M and G classes were mostly specific for the Fab region of rabbit Ig, although a small but measurable amount of Fc-specific antiglobulin was present and was of high relative avidity. The low normal serum IgA anti-IgG activity detected was essentially nonspecific. We conclude that normal antiglobulins differ from "rheumatoid factors" in their specificity and that this may relate to different roles in health and disease.

Animals↗
PubMed1986

Occurrence of autoantibodies to intermediate filament proteins in human visceral leishmaniasis and their induction by experimental polyclonal B-cell activation.

Fifteen sera of patients with visceral leishmaniasis were investigated for the occurrence of autoantibodies. They were found in high incidence and titre, and with specificity to the intermediate filament (INFIL) proteins vimentin (12 out of 15 with a titre higher than 1:10) and keratin (9 out of 15 with a titre higher than 1:10) as well as to speckled anti-nuclear antigens (ANA). Additionally, supernatants of Leishmania major and Leishmania donovani cultures containing soluble parasite-derived antigens were mitogenic to cultures of mononuclear cells (MNC) obtained from healthy donors without specific antibodies to leishmanial antigens. The activation of MNC resulted in significant immunoglobulin production, some of which demonstrated autoantibody specificity to INFIL. The co-operation of monocytes, T cells and B cells was required in order to obtain maximal stimulation. The importance of polyclonal B-cell activation for the genesis and occurrence of autoantibodies in visceral leishmaniasis is discussed.

Antigens, Protozoan↗
PubMed1985

The production of small IgG aggregates by glutaraldehyde cross-linking.

Reaction conditions have been determined for the production of soluble IgG polymers in the size range 10 S to 30 S by covalent cross-linking with glutaraldehyde. This size range is comparable with that of the immune complexes which are frequently found in the circulation of patients with certain autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. The yield of IgG aggregates in this size range is far greater than has been reported for cross-linking by other bifunctional reagents or for aggregation by heating. Glutaraldehyde cross-linked IgG polymers are stable and biologically reactive. They can also be labelled with fluorescein and freeze-dried with minimal loss of integrity or reactivity.

Aldehydes↗
PubMed1985

Soluble IgG aggregates produced by heating remain stable on freeze-drying.

IgG aggregates produced by heating gamma globulin solutions were freeze-dried, kept at 4 degrees C and reconstituted up to 4 months later. By comparison with frozen (-20 degrees C) preparations, only minimal changes in biological reactivity and in physical integrity occurred during this period. These results demonstrate that freeze-dried preparations of heat-aggregated IgG are potentially useful as a reference reagent for the comparative evaluation and standardisation of immune complex assays.

Antigen-Antibody Complex↗
PubMed1985

Circulating immune complexes and rheumatoid arthritis: a comparison of different assay methods and their early predictive value for disease activity and outcome.

The performance of four different assays for circulating immune complexes-the C1q solid phase method, one using protein A and one using anti-IgG, C1q PEG, and the 2% PEG method-were compared in 61 patients with early rheumatoid arthritis followed up for two years. There were weak but statistically significant correlations between the results from some of the pairs of assays, but the changes over time from any single assay did not correlate with those from any of the other assays. None of the assays predicted either future disease activity, as measured by subsequent ESR, CRP, and articular index; or functional outcome, as measured by wrist extension, Steinbocker functional capacity, and the Stanford health assessment questionnaire. It is unlikely therefore that the measurement of immune complexes is of value in predicting early outcome in patients with rheumatoid arthritis.

Adult↗
PubMed1985

Anti-intermediate filament antibodies, antikeratin antibody, and antiperinuclear factor in rheumatoid arthritis and infectious mononucleosis.

Sera from patients with rheumatoid arthritis (RA), patients with infectious mononucleosis (IM), and blood donors were tested by indirect immunofluorescence for the presence of antikeratin antibody (AKA), antibody to cytoskeletal intermediate filaments of prekeratin or vimentin type (AIFA) and antiperinuclear factor (APF). In 81.9% of the RA sera and 92.5% of the IM sera AIFA of IgM class was found at titres up to and in some cases exceeding 1/160. In blood donors the incidence of AIFA was 26%, at titres not exceeding 1/20. AKA and APF, always of IgG class, were found in 54.2% and 73.6% of rheumatoid sera. A weak correlation was found in RA between the incidence of AIFA and APF. AKA was not present in either IM or blood donor sera, and APF was found in only 2.5% and 3.2% of IM or blood donors respectively.

Antibodies, Antinuclear↗
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

Incidence of anti-intermediate filament antibody in serum samples of students with suspected glandular fever.

Serum samples from 40 students with suspected infectious mononucleosis were tested for the presence of antibodies to intermediate filaments (AIFA) of the cytoskeleton. Twenty had antibodies to the Epstein-Barr virus capsid antigen before their illness, and during it their sera remained negative by the Paul-Bunnell test. The other 20 patients did not have antibodies to the Epstein-Barr virus capsid antigen before their illness and seroconverted during the illness. These patients (true infectious mononucleosis group) developed positive Paul-Bunnell tests. Sera from normal subjects (blood donors) were also tested for AIFA. AIFA was present in titres greater than 1/10 in 80% of the infectious mononucleosis group (mean titre 1/40-1/80), 10% of the Paul-Bunnell negative glandular fever group, and 8.5% of the normal blood donors.

Adult↗
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↗
PubMed1979

Distribution of actin and myosin in muscle and non-muscle cells.

Specific anti-actin and anti-myosin antibodies were shown to react in single and double immunofluorescence sandwich tests with identical sites in non-muscle cells in frozen sections of tissues and in cultured cells. In tissues, both antibodies reacted with liver cell membranes, parts of renal glomeruli, brush borders and peritubular fibrils of renal tubules, brain synaptic junctions, and membranes of lymphoid cells in thymic medulla, lymph nodes and spleen. Both antibodies reacted strongly with long parallel cytoplasmic fibrils in cultured fibroblasts, and with disrupted fibrils in cytochalasin-B treated cells. In neuroblastoma cells both antibodies gave prominent staining of growth cones and microspikes. The observation that the distribution of myosin parallels that of actin in non-muscle cells argues strongly in favour of a functional interaction between the two molecules in the generation of contractile activity in non-muscle cells.

Actins↗