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Biomedical subjects

V R Winrow

Publications and source records attributed to V R Winrow.

32 records · Page 2Linked to original sources
PubMed1990

Effect of a free sulphydryl group on expression of HLA-B27 specificity.

Sequence studies indicate that the alpha-1 domain of the HLA-B27 molecule has a characteristic unpaired cysteine residue at position 67, adjacent, because of secondary structure, to a lysine at position 70. Simple chemical considerations predict that this cysteine should have an exceptionally reactive sulphydryl group. We have shown by ELISA and flow cytometry that the binding of some monoclonal antibodies to B27 on lymphoid cell lines can be inhibited by reagents which react with sulphydryl groups. However this inhibition is never complete: the evidence suggests 2 forms of B27 molecule, one of which is already blocked. We propose that some HLA molecules with oxidised sulphydryls are recognised as different from the reduced forms. Whether they are also recognised as foreign will depend on an individual's history of thymic learning. Oxidation to 'foreign' HLA in the adult is likely to predispose to inflammatory reactions.

Antibodies, Monoclonal↗
PubMed1989

Status of an unpaired thiol group on the HLA-B27 epitope.

Sequence analysis and site-directed mutagenesis of HLA-B27 indicate an unpaired cysteine at position 67 of the hypervariable region corresponding to its serologically defined, disease-associated epitope. We investigated whether chemical modification of this thiol group affected the serological reactions of B27. B27-positive cells were treated with thiol-blocking agents and then tested for recognizable B27 expression. Anti-HLA-B27 alloantisera and monoclonal antibodies were used in cytotoxicity, absorption, and cellular ELISA (cELISA). The semi-quantitative cytotoxicity-based assays showed some decrease in both B27 and controls. However, cELISA indicated that the inhibition of B27 was significantly greater than control antigens, and dependent on thiol-blocker concentration. This suggests that a proportion of HLA-B27 molecules have a free, reactive thiol at the antibody-defined epitope. Incomplete inhibition by thiol-blocking agents indicates that the remainder are inaccessible.

Antibodies, Monoclonal↗
PubMed1988

The role of HLA-B27 in arthritis.

We postulate (Table I) that ReA is an antigen or immune complex induced condition caused by chronic intracellular bacterial infection at a distant site. The main predisposing factor is a failure to resist this infection. If the bacteria happen to carry MF, the inflammation is exacerbated in B27 positive patients. In contrast AS occurs in individuals who lack immunity to MF and eventually become infected by an intracellular organism which synthesizes it (virus or plasmid?). HLA-B27 acts only at the site of inflammation.

Arthritis↗
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↗
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↗
PubMed1985

Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. II. Phenotypic characterisation of mononuclear cells forming Facb rosettes in RA.

We have previously reported an increased proportion of Facb-rosette forming cells in the peripheral blood of patients with rheumatoid arthritis in comparison with healthy controls. The present study investigates the surface phenotype of these cells by means of monoclonal antibodies and a variety of rosetting and lymphocyte fractionation techniques. Facb-R+ cells were found to lack surface markers characteristic of T and B lymphocytes. Studies with monoclonal reagents showed a positive reaction with OKIa1, OKM1, and another monocyte-specific antibody. Fac-R+ cells were recognised by anti-HLA-DR reagents but did not bind the monoclonal antibody 17.15 that recognises a determinant on HLA-DR antigens expressed by lymphocytes but not monocytes. These results show that Facb-R+ cells share certain surface characteristics with monocytes, though they are not phagocytic. These observations are consistent with an accessory role for Facb-R+ cells in the immune response.

Antibodies, Monoclonal↗
PubMed1985

Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. III. Immunoregulatory function associated with Facb rosette-forming cells.

A subpopulation of mononuclear cells (PBMNC) that expresses Fc receptors with specificity for the C gamma 2 region of IgG may be detected by rosette formation with calf erythrocytes coated with the Facb fragment of rabbit IgG. These Facb-R+ cells are found in increased numbers in the peripheral blood of patients with rheumatoid arthritis (RA). Studies have been carried out to identify the functional properties of these cells in healthy and rheumatoid subjects. Facb-R+ cells were shown to lack both natural killer and antibody-dependent cytotoxic activity. Depletion of Facb-R+ cells from both healthy and rheumatoid PBMNC resulted in a marked suppression of pokeweed mitogen (PWM) stimulated IgG synthesis but had no effect on T cell proliferation induced by phytohaemagglutinin, concanavalin A, or PWM. The addition of Facb fragments to PBMNC cultures also caused inhibition of PWM-driven IgG production. In this assay rheumatoid PBMNC were significantly less sensitive to Facb-mediated suppression than healthy control cells. Our results suggest that Facb-R+ cells are involved in the antibody-mediated feedback regulation of immunoglobulin synthesis and that this mechanism is impaired in patients with RA.

Antibody Formation↗
PubMed1980

Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. I. An increased subpopulation of cells in rheumatoid arthritis detected with Facb rosettes.

The chronic production of IgM and IgG antiglobulins is a major feature of rheumatoid arthritis. This implies an abnormal interaction between rheumatoid leucocytes and IgG. A novel rosette assay employing rabbit Facb-coated calf red blood cells has been developed to study receptors for IgG on peripheral blood lymphocytes. Cells were obtained from groups of patients with rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and healthy control subjects. Receptors for Facb were found on an increased proportion of lymphocytes from RA patients compared with the other groups tested. It has been shown that the Facb rosette assay detects a subpopulation of lymphocytes bearing receptors for the Fc region of IgG. This receptor is clearly capable of recognising and binding only the C gamma 2 domain within the Fc region. As such it shows different specificity from some other Fc receptors detected on mononuclear cells. The number of Facb rosette-forming lymphocytes in an individual sample correlated well with the number of cells bearing 'high avidity' Fc receptors. However, the incidence of these cells in RA patients could not be correlated with disease activity, disease duration, or levels of IgM and IgG rheumatoid factor. Thus increased Facb rosette cells may represent a fundamental imbalance of the immune response in patients with rheumatoid arthritis.

Arthritis, Rheumatoid↗