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Biomedical subjects

S Kaveri

Publications and source records attributed to S Kaveri.

At least 19 recordsLinked to original sources
PubMed2001

Effect of human immunoglobulins on the immunogenicity of porcine bioprostheses.

BACKGROUND: Glutaraldehyde fixation (GT) is known to reduce immunologic reactions and tissue degeneration after implantation in humans. Sterilization after glutaraldehyde fixation (G-ST) improves the safety and reduces the tendency of GT valves to calcify. Intravenous immunoglobulins (IVIg) have been shown to reduce xenogeneic response against porcine tissue. We have investigated the effect of these fixation procedures combined with and without IVIg on the antigenicity of bioprostheses. METHODS: Lewis adult rats were implanted subcutaneously with a fresh, GT, or G-ST porcine heart valve pre- or posttreated with different amounts of IVIg. We followed by enzyme-linked immunosorbent assay and IgM and IgG titers against protein extracts from the porcine heart valves after implantation. Cellular reactivity was assessed in xenogeneic lymphoendothelial coculture experiments. Calcification content was also examined. RESULTS: Glutaraldehyde fixation partially decreased the humoral response against proteins of the implant but elicited a cellular xenogeneic response. Sterilization reduced these reactivities, but retained antigenicity. Intravenous immunoglobulin postincubated with GT valves before implantation reduced the antigenicity of the tissue to the same extent as G-ST valves, but had no effect on valvular tissue calcification. CONCLUSIONS: Our studies demonstrate that IVIg or the sterilization procedure (ST) reduced the cellular response against glutaraldehyde-fixed valves (GT), whereas reduced calcification was observed only with ST.

Animals↗
PubMed1998

Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice.

Atherosclerosis is associated with immune activation. T cells and macrophages infiltrate atherosclerotic plaques and disease progression is associated with formation of autoantibodies to oxidized lipoproteins. In the apo E knockout mouse, a genetic model of cholesterol-induced atherosclerosis, congenital deficiency of macrophages, lymphocytes, or interferon-gamma receptors result in reduced lesion formation. We have now evaluated whether immune modulation in the adult animal affects disease development. Injections of 7-wk-old male apo E knockout mice with polyclonal immunoglobulin preparations (ivIg) during a 5-d period reduced fatty streak formation over a 2-mo period on cholesterol diet by 35%. Fibrofatty lesions induced by diet treatment for 4 mo were reduced by 50% in mice receiving ivIg after 2 mo on the diet. ivIg treatment also reduced IgM antibodies to oxidized LDL and led to inactivation of spleen and lymph node T cells. These data indicate that ivIg inhibits atherosclerosis, that it is effective both during the fatty streak and plaque phases, and that it may act by modulating T cell activity and/or antibody production. Therefore, immunomodulation may be an effective way to prevent and/or treat atherosclerosis.

Adjuvants, Immunologic↗
PubMed1998

Selective impairment of serum antibody repertoires toward muscle and thymus antigens in patients with seronegative and seropositive myasthenia gravis.

We analyzed the antibody (Ab) repertoires of IgM and IgG of patients with seropositive and patients with seronegative myasthenia gravis (MG) toward self antigens by means of a quantitative immunoblotting technique using normal human tissue extracts as sources of self antigens. Repertoires of reactivities of IgG and IgM with liver, kidney and stomach antigens were conserved between myasthenic patients and controls. IgG and IgM Ab repertoires toward muscle antigens differed significantly between patients with seropositive MG and healthy donors, as assessed by multiparametric statistical analysis. Patterns of Ab reactivities to muscle antigens were similar in patients with seronegative MG and healthy controls. Antibody repertoires of IgG and IgM toward thymus antigens of both seropositive and seronegative MG patients, differed significantly from those of healthy individuals. Our results indicate that MG is characterized by a selective impairment of self-reactive Ab repertoires toward muscle and thymus antigens. The observation that self-reactive Ab repertoires toward thymus antigens are similar in patients with seropositive and seronegative MG suggests that both forms of MG share common immunopathological features.

Adult↗
PubMed1998

Intravenous immunoglobulins for therapeutic use contain anti-idiotypes against xenophile antibodies and prolong discordant graft survival.

Xenotransplantation between discordant species leads to a graft survival of a few minutes, due to binding of natural antibodies to the xenogeneic endothelial cells, complement activation, and endothelial cell activation. Polyclonal human immunoglobulins for intravenous use (IVIg) from normal donors have been proven effective in a variety of antibody-mediated disorders and contain anti-idiotypic antibodies directed against a number of disease-associated and natural antibodies. We have shown that administration of IVIg delays rejection of a guinea pig heart to a rat. We demonstrate herein that IVIg can inhibit the binding of xenoreactive rat IgG antibodies to guinea pig endothelial cells. This inhibition is likely due to the presence, among IVIg, of anti-idiotypic antibodies as F(ab')2 fragments of IVIg were as effective as whole IVIg. In addition, natural anti-endothelium rat antibodies were retained on a column of F(ab')2 fragments of IVIg coupled to Sepharose. The degree of inhibition of binding of IgG natural antibodies correlated with the survival of the xenograft when IVIg was administered prior to transplantation. Thus IVIg prolong xenograft survival through idiotypic-anti-idiotypic interactions with natural xenoreactive antibodies of the IgG isotype.

Animals↗
PubMed1998

Modulation of endothelial cell function by normal polyspecific human intravenous immunoglobulins: a possible mechanism of action in vascular diseases.

Intravenous immunoglobulin (IVIg) is increasingly used in the treatment of autoimmune and inflammatory diseases, including vasculitides and Kawasaki disease. However, the outcome of IVIg interaction with endothelial cells of the vascular bed is not clear as yet. We have investigated the effect of IVIg on the in vitro activation of human endothelial cells, as assessed by cell proliferation and reverse transcription-polymerase chain reaction-detected expression of mRNA coding for adhesion molecules (intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1), chemokines (monocyte chemoattractant protein-1, macrophage colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor), and proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6). IVIg inhibited proliferation of endothelial cells in a time-dependent manner. This effect was dependent on both Fc and F(ab')2 fragments of the immunoglobulin molecule and was fully reversible. Tumor necrosis factor-alpha and interleukin-1beta also inhibited thymidine incorporation, but to a lesser degree. IVIg had no effect on basal levels of mRNA coding for the adhesion molecules, chemokines, and proinflammatory cytokines. IVIg fully down-regulated the expression induced by tumor necrosis factor-alpha or interleukin-1beta of mRNA coding for these molecules. Thus, blockade of cellular proliferation and of cytokine-induced expression of adhesion molecules, chemokines, and cytokines may explain the therapeutic effect of IVIg in vascular and inflammatory disorders.

Cell Adhesion Molecules↗
PubMed1997

Modulation of autoimmune responses by intravenous immunoglobulin (IVIg).

Significant progress has been made in understanding the mechanisms by which intravenous immunoglobulins (IVIg) exert immunomodulatory effects in the treatment of autoimmune diseases. A unique property of immunoglobulins is the diversity of variable (V) regions. The evidence discussed in this communication supports our notion that the diversity of V regions in IVIg preparations is a determining factor for the anti-inflammatory substitutive and immunomodulatory functions of IVIg therapy. We have demonstrated the presence in IVIg, of anti-idiotypic antibodies directed against various autoantibodies. The ability of IVIg to interact through V regions with complementary V regions of antibodies and antigen receptors as well as with relevant soluble and surface molecules provides the basis for inducing the selection of immune repertoires. The study of the mechanisms by which IVIg mediates selection of autoreactive repertoires is essential for our understanding of the mechanisms underlying the emergence of pathological autoimmunity and of the physiological role of natural antibodies in the establishment and maintenance of tolerance to self and homeostasis of autoreactivity in healthy individuals.

Animals↗
PubMed1996

Antibodies to a conserved region of HLA class I molecules, capable of modulating CD8 T cell-mediated function, are present in pooled normal immunoglobulin for therapeutic use.

Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune diseases and the prevention of infections and of graft versus host reactions in recipients of allogeneic bone marrow transplants. The immunomodulatory effects of IVIg are largely dependent on their ability to interact with membrane molecules of lymphocytes. We report here that IVIg recognizes the B07.75-84 peptide, corresponding to a conserved region of the alpha I helix of the first domain of HLA-B7 01, which represents a nonpolymorphic determinant of HLA class I molecules. Intact IVIg and its F(ab')2 fragments bound to the peptide as well as to purified soluble HLA and to HLA on a human T cell line. Binding of IVIg to HLA was assessed by ELISA, immunofluorescence, and real-time analysis of the interaction using the BIAlite system. The binding of antipeptide antibodies to HLA was inhibited by free peptide. Antipeptide antibodies isolated from IVIg by affinity chromatography inhibited CD8 cell-mediated cytotoxicity of an influenza virus-specific human T cell line. The presence in IVIg of antibodies to critical regions of HLA class 1 molecules suggests a possible role for IVIg in modulation of class-I-restricted cellular interactions in the immune response.

Amino Acid Sequence↗
PubMed1996

[Regulation of autoreactivity by the idiotypic network and therapeutic modulation of autoimmunity by polyvalent intravenous immunoglobulins (IgIV)].

A beneficial effect after intravenous administration of immunoglobulins (IgIV) has been reported in a large number of autoimmune diseases, whether mediated by autoantibodies or T cells. The short-term immunoregulator effect of IgIV, mediated by interaction of the Fc fragment of the immunoglobulins with the Fc receptors on the surface of leukocytes has been thoroughly described. The arguments presented in this review indicate that one of the consequences of IgIV administration is to restore regulation of autoreactivity via a network of interactions between "natural" autoreactive IgG in the infusion and elements of the immune system. Via this network, IgIB can i) produce transient or long-term suppression of specific autoreactive clones and stimulation of reactive B cells with IgIV fragments F(ab); ii) restore normal fluctuations in natural autoantibody titre in the serum; and iii) modulate synthesis of cytokine secretion.

Autoimmune Diseases↗
PubMed1995

Catalytic activity of anti-thyroglobulin antibodies.

Thyroglobulin (Tg)-specific autoantibodies from a patient with Hashimoto's thyroiditis hydrolyzed radiolabeled Tg, shown by production of several smaller sized products on SDS electrophoresis gels. The apparent Km value for Tg was in the nanomolar range, a property typical of an Ab combining site. The Tg antibodies also hydrolyzed tripeptide-methylcoumarinamide (MCA) substrates with lower affinity, displaying a preference for Arg-MCA and Lys-MCA containing conjugates. The hydrolysis of one of these conjugates, Pro-Phe-Arg-MCA, was inhibited competitively by Tg, suggesting a catalytic site located in the Ab combining site. In control experiments, 1) the hydrolytic activities were removed by immunoadsorption with immobilized anti-human IgG; 2) IgG depleted of the Tg-specific Abs by affinity chromatography did not display Tg and Pro-Phe-Arg-MCA hydrolyzing activities; and 3) the peptide-MCA hydrolyzing activity tracked exactly with the 150-kDa IgG peak on a gel filtration column run in denaturing solvent (6 M guanidine chloride).

Amino Acid Sequence↗
PubMed1994

Immune modulating effects of intravenous immunoglobulin (IVIg) in autoimmune diseases.

Administration of intravenous immunoglobulins (IVIg) have now been reported to be beneficial in a large number of autoimmune diseases, whether mediated by autoantibodies or by T cells. We have proposed that the immunoregulatory effect of IVIg in autoimmune diseases is dependent on the selection of recipient's immune repertoires by variable (V) regions of infused immunoglobulins. Thus: (a) IVIg contains antibodies reactive with idiotypes of natural and disease-related autoantibodies and surface immunoglobulins of B cells; IVIg also contains antibodies reactive with idiotype, framework and constant regions of the beta chain of the alpha beta T cell receptor; (b) infusion of IVIg results in transient or long-lasting suppression of specific autoantibody clones in vivo and in stimulation of a distinct subset of B cells reactive with F(ab')2 fragments of IVIg; (c) infusion of IVIg alters the general "architecture" of the network as assessed by studying the kinetic patterns of spontaneous fluctuations of natural autoantibodies in serum; (d) infusion of normal mouse Ig in healthy adult mice selects expressed immune repertoire by removing late pre-B and B cells in the bone marrow, mostly those expressing D proximal VH genes, and by activating distinct subsets of B cells and CD4+ T cells in the spleen; and (e) infusion of IVIg results in a modulation of synthesis and release of cytokines. Although dependent on the V-region reactivities (composition) or injected preparations, these effects probably also require that the infused immunoglobulin contains an intact Fc moiety. This review focuses on autoimmune and inflammatory diseases in which IVIg therapy has been beneficial. Recent recommendations from a committee of experts for IVIg therapy have been pointed out.

Adjuvants, Immunologic↗
PubMed1989

Revised immune network concepts.

The idiotype network concept needs to be revised in order to be in agreement with current data on protein/protein interactions, with the phenomenon of T and B cell recognition of idiotopes, and with the failure of certain anti-idiotypes to stimulate a given immune response. It is proposed that the distinction among Ab2 alpha, beta, and gamma is abandoned, as well as the concept of an internal image idiotope which mimics the three-dimensional shape of nominal antigen. In place of these definitions, the concept of "network antigen" is introduced. Network antigens are potentially the entire repertoire of anti-idiotypes. However, their biological effectiveness is controlled and established by two factors: (i) the affinity to the idiotype Ig receptor; and (ii) the preexisting regulatory network segment that controls the outcome of immune stimulation or suppression. Screening for effective idiotype therapeutic agents has to be done with panels of anti-idiotype and idiotype antibodies in order to establish correlations between idiotope expression and disease progression. Recognizing the importance of network segments will be the first step in the direction toward a rational design of idiotype-based therapies.

Humans↗
PubMed1989

Internalization of beta-adrenergic receptor in A431 cells involves non-coated vesicles.

To characterize the mechanism of internalization of beta-adrenergic catecholamine receptors on human epidermoid A431 carcinoma cells, their distribution was analyzed by immunocytochemistry using the monoclonal anti-receptor antibody BRK2. In preconfluent cultures, the receptors appeared to be randomly distributed on the cell surface. Exposure to the agonist isoproterenol induced an overall decrease in the number of cell surface receptors as determined by binding experiments and visualized by immunofluorescence. When cells were incubated at 4 degrees C with BRK2 and anti-mouse IgG-gold and then transferred at 37 degrees C, non-coated invaginations and vesicles were labeled. The addition of isoproterenol resulted in an increased rate of internalization of the receptor-BRK2-anti-IgG-gold complex. When incubation with the two antibody reagents was prolonged (with or without isoproterenol), non-coated vesicles fused in the endosomal compartment, and receptors were transferred to multivesicular bodies and lysosomes. At no stage in this process was there any indication that clathrin-coated pits or vesicles participated. Furthermore, we found that an intracellular potassium depletion treatment known to inhibit endocytosis, did not affect the normal pattern of desensitization of beta-adrenergic receptors.

Antibodies, Monoclonal↗
PubMed1988

The beta 2-adrenergic receptors of human epidermoid carcinoma cells bear two different types of oligosaccharides which influence expression on the cell surface.

The beta 2-adrenergic receptors of the human epidermoid carcinoma A431 cells reside on two polypeptide chains revealed by photoaffinity labelling with [125I]iodocyanopindolol-diazirine. These proteins correspond to two distinct populations of N-asparagine-linked glycoproteins: the 55-52 kDa molecules are associated with complex carbohydrate chain(s), the 65-63 kDa component with polymannosidic carbohydrate chain(s). Both types of receptors are present in preconfluent cells, but only the polymannosidic type is found in the postconfluent cells. Moreover, complex chains appear to be associated with the receptors with the highest affinity for (-)-isoproterenol and polymannosidic chains with the receptors with the lowest affinity for this agonist. the carbohydrate moiety of the beta-adrenergic receptor is involved in the expression and function of the beta 2-adrenergic receptors at the surface of the A431 cells, since tunicamycin and monensin, complete and partial inhibitors of glycosylation respectively, diminish the number of binding sites at the cell surface and increase the total number of sites in the cell. In these conditions a diminution of cyclic AMP accumulation is also observed.

Adrenergic beta-Antagonists↗