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S V Kaveri

Publications and source records attributed to S V Kaveri.

At least 73 records · Page 4Linked to original sources
PubMed1994

Anti-CD4 activity of normal human immunoglobulin G for therapeutic use. (Intravenous immunoglobulin, IVIg).

The effects of intravenously administered normal immunoglobulin G (IVIg) in autoimmune diseases are dependent on the ability of IVIg to interact with surface molecules of lymphocytes. In the present study, we demonstrate the presence of anti-CD4 activity in IVIg by showing the ability of IVIg to bind to CD4 and to inhibit CD4-dependent cellular functions. Binding of IVIg to recombinant soluble human CD4 was assessed by ELISA, immunoblotting and real time analysis of complex formation. Anti-CD4 antibodies isolated from IVIg by affinity-chromatography bound to human CD4+ T cells. These anti-CD4 antibodies inhibited proliferative responses in MLR and infection of CD4+ human T cells with HIV. These results indicate that IVIg contains antibodies reactive with human CD4 and that these anti-CD4 antibodies exhibit biological functions. The presence of anti-CD4 antibodies in IVIg may be relevant to the immunoregulatory effects of normal polyspecific immunoglobulin G.

Adjuvants, Immunologic↗
PubMed1993

Expression and control of the natural autoreactive IgG repertoire in normal human serum.

We have investigated the autoreactive repertoire expressed by serum IgG of healthy individuals of various age groups using a large panel of self antigens. Natural IgG autoantibodies against all self antigens of the panel were found in the purified IgG fraction of the serum of all donors that were tested. The mean binding activity to self antigens of IgG of pregnant women was higher than that of IgG purified from the serum of infants, young adults and aged individuals. No increase in IgG autoreactivity was observed with aging neither in the purified IgG fraction of serum nor in whole serum. Whereas autoantibody activity was easily detectable in purified IgG, it was low in serum. No difference was observed, however, between the binding activity of purified IgG and of IgG in serum in the case of foreign antigens nor in the case of anti-thyroglobulin autoantibodies of patients with hashimoto's thyroiditis. Purified IgM from normal serum bound to F(ab')2 fragments of autologous IgG in a dose-dependent fashion and inhibited the binding of autologous IgG to self antigens. Our results thus indicate that autologous IgM contributes to regulate expression of the natural IgG autoreactive repertoire through V region-dependent interactions, resulting in low levels of IgG autoreactivity in serum under physiological conditions.

Adult↗
PubMed1993

Monoclonal anti-idiotypic antibodies against human anti-thyroglobulin autoantibodies recognize idiotopes shared by disease-associated and natural anti-thyroglobulin autoantibodies.

Monoclonal murine anti-idiotypic antibodies generated against purified human anti-thyroglobulin (TG) antibodies from a patient with Hashimoto's thyroiditis recognized two major clusters of idiotopes (1C2 and 1B1) on human anti-thyroglobulin antibodies which were framework and paratope-related. A survey of affinity-purified autoantibodies from Hashimoto's patients indicated that the 1C2 and 1B1 idiotopes are expressed on the disease-associated anti-TG antibodies from several patients. 1C2 and 1B1 idiotopes are also detected on affinity-purified anti-TG antibodies isolated from serum of healthy donors and with therapeutic preparations of immunoglobulins obtained from plasma pools of healthy individuals. The observation that both framework and paratope-related idiotopes are shared by natural and patients' autoantibodies suggests that the anti-TG autoantibodies found in sera of patients with Hashimoto's disease represent an abnormal expansion of normal autoreactive B cell clones rather than the emergency of an antigen-driven, disease-specific B cell response.

Animals↗
PubMed1993

Age-related changes in specificity of human natural autoantibodies to thyroglobulin.

We have analysed the epitopic and idiotypic specificity of thyroglobulin antibodies in infants, young adults, aged subjects and pregnant women in order to evaluate the changes that occur in the autoantibody repertoire with age in physiological situations. No increase in IgG anti-Tg autoreactivity in whole serum and purified IgG from serum was observed with aging. However, IgG from elderly individuals exhibited increased reactivity, as compared to other groups of donors, against particular epitopes commonly recognized by both natural and disease-associated Tg-autoantibodies. The acquisition of a distinct epitopic reactivity in aged individuals suggests that qualitative rather than quantitative criteria could characterize alteration in regulation of the autoreactive B-cell repertoire that occurs with aging. No correlation was observed between the age of the donors and expression of a thyroid disease-associated idiotype (T44 Id) by hTg-autoantibodies. The expression of T44 Id on IgG obtained from serum of a small number of pregnant women may be an effect of the modifications of immune system function in pregnancy, which could lead to increased incidence of autoimmunity during pregnancy or in the post-partum period.

Adult↗
PubMed1993

Normal polyspecific immunoglobulin G (IVIg) in the treatment of autoimmune diseases.

Infusion of intravenous immunoglobulin (IVIg) has resulted in clinical improvement and/or a fall in autoantibody in a number of autoimmune and inflammatory diseases. Several lines of evidence demonstrate that IVIg may react with disease-associated autoantibodies through idiotypic interactions. In addition, infusion of IVIg results in changes in the expressed autoantibody repertoire that are dependent on interactions between variable regions of infused IgG and autoantibodies and in the subsequent alterations in the regulatory function of immune networks. Thus, pooled normal immunoglobulin restored in a patient with autoimmune thyroiditis the dynamics of spontaneous fluctuations of serum autoantibodies characteristic of physiological conditions. The ability of IVIg to interact with V regions of autoantibodies and with surface molecules of lymphocytes in vitro provides a basis for the selective modulation of B-cell clones observed in patients treated with immunoglobulins. The natural intrinsic complexity of IVIg provides a physiological rationale for immunoregulatory therapy of autoimmune disease.

Antibodies, Anti-Idiotypic↗
PubMed1993

Human immunoglobulin preparations for intravenous use prevent experimental autoimmune uveoretinitis.

We have evaluated the effect of human Igs for intravenous use (IVIg) on the onset and development of experimental autoimmune uveoretinitis (EAU), a T cell-dependent autoimmune disease induced in rats by a single immunization with retinal S-antigen (S-Ag). Five consecutive daily infusions of IVIg, starting on the same day as S-Ag immunization, protected (Lewis x Brown-Norway) F1 rats against EAU. The prevention of EAU was IVIg-specific, i.e. mediated by pooled human IgG from multiple donors, since neither infusions of BSA nor infusions of pooled Ig from only two healthy individuals were effective. Treatment with IVIg decreased lymphocyte proliferative and antibody responses to S-Ag and the proliferative response to concanavalin A. Lack of proliferation was not dependent upon generation of suppressor cells. Lymph node (LN) cells from IVIg-treated and S-Ag-immunized animals neither proliferated nor secreted IL-2 in response to S-Ag but proliferated when co-cultured with LN cells from rats immunized with S-Ag. Our findings are compatible with an induction of a state of functional inactivation/anergy of T lymphocytes by infusions of IVIg. This functional inactivation may be due to the presence in IVIg of antibodies that bind both in vivo and in vitro to rat lymphocytes. Results from the present study suggest a novel mechanism by which IVIg may be beneficial in human autoimmune diseases.

Animals↗
PubMed1993

Antibodies to the CD5 molecule in normal human immunoglobulins for therapeutic use (intravenous immunoglobulins, IVIg).

IVIg are increasingly used for the treatment of autoimmune diseases. In the present study, we show that IVIg contain antibodies directed against CD5, a cell surface molecule of T cells which is also a marker of the autoantibody-producing CD20+ ('B-1') subset of B lymphocytes. Antibodies to the CD5 molecule were demonstrated in IVIg by the ability of therapeutic preparations of IVIg to inhibit the binding of labelled CD5 MoAb to the CD5-expressing human T cell line H9. Preincubation of H9 cells with IVIg or with F(ab')2 fragments prepared from IVIg resulted in dose-dependent inhibition of the binding of CD5 antibody. The presence in IVIg of antibodies to the CD5 molecule was further confirmed by the binding of IVIg to mouse L cells that expressed human CD5 molecules following a stable transfection with CD5 cDNA. Human CD5 antibodies in IVIg provide therapeutic immunoglobulin preparations with the potential of modulating T cell functions through CD5, and of regulating the expression of B cell subsets expressing CD5. This may have implications for the treatment of autoimmune diseases.

Animals↗
PubMed1993

Polyreactivity is a property of natural and disease-associated human autoantibodies.

Polyreactivity was earlier recognized as a feature of naturally expressed autoantibodies in serum. In the present study, we have compared the reactivity on a panel of self antigens of affinity-purified anti-DNA and anti-thyroglobulin (TG) IgG autoantibodies from the serum of patients with systemic lupus erythematosus (SLE) and autoimmune thyroiditis with their affinity-purified counterparts isolated from the serum of healthy individuals. Anti-DNA autoantibodies exhibited a similar degree of polyreactivity whether originating from patients or from healthy adults. Natural anti-TG autoantibodies were also found to be polyreactive. Anti-TG autoantibodies from patients with Hashimoto's thyroiditis showed little or no polyreactivity. Natural anti-TG autoantibodies were equally polyreactive whether or not they belonged to a fraction of normal IgG that is connected through V regions with other IgG molecules from the same source. These results indicate that polyreactivity of autoantibodies is a feature that does not allow one to distinguish between natural and disease-associated autoantibodies as well as between V-region-connected and unconnected autoantibodies.

Amino Acid Sequence↗
PubMed1992

A V region-connected autoreactive subfraction of normal human serum immunoglobulin G.

Mouse and human natural IgM autoantibodies have been shown to be polyreactive and "connected" through V region-dependent interactions. In the present study, we have identified a connected subfraction of normal human serum IgG by using affinity chromatography of F(ab')2 fragments of pooled IgG (IVIg) or of IgG from a single donor on Sepharose-bound F(ab')2 fragments of the same source of IgG. The connected fraction of IgG exhibited a high content of autoantibodies directed against a wide panel of evolutionarily conserved self antigens and of self antigens that may be targets of autoantibodies in autoimmune diseases. Connected IgG also contained higher amounts of antibodies directed against commonly encountered microbial antigens than unfractionated IgG. The connected fraction did not, however, differ from unchromatographed IgG nor from non-connected IgG in its content of antibodies to vaccinal antigens and to distant foreign antigens. Thus, in humans as in mice, connectivity is a prominent feature of autoantibodies. Our observations are suggestive of a tight control by IgG of the expressed autoreactive repertoire in healthy individuals and strengthen the concept that the therapeutic infusion of pooled normal IgG (IVIg) may be effective in autoimmune diseases by bringing to patients normal regulatory components of the immunoglobulin network.

Autoantibodies↗
PubMed1992

Cryptic T cell epitopes in polymorphic immunoglobulin regions: evidence for positive repertoire selection during fetal development.

The adult T cell repertoire is the result of positive and negative intrathymic selective processes. Since non-self antigens are not present in the thymus, self peptides are believed to play a role in the thymic T cell selection. T cell lines raised against a peptide from the second complementarity-determining region (CDR2) of the S107 germ-line immunoglobulin (Ig) do not respond to the intact Ig, indicating that in adult animals this CDR2 epitope is cryptic in the context of intact S107 Ig. To show that the response to self Ig peptide is the result of positive selection, the fetal expression of the S107 germ-line Ig was suppressed by maternal anti-idiotype (Id) injection. Id S107-suppressed mice responded poorly to the CDR2 peptide, indicating that S107 Ig selects positively T cells responding to a polymorphic self epitope. Cross-reactivity of cryptic self Ig with non-self epitopes could be a mechanism to increase the T cell repertoire for foreign antigens.

Amino Acid Sequence↗
PubMed1992

Modulation of autoimmunity by intravenous immune globulin through interaction with the function of the immune/idiotypic network.

Infusion of intravenous immune globulin (IVIG) has resulted in clinical improvement and/or a fall in autoantibody titer in a number of autoimmune diseases in which direct or indirect evidence suggests a pathogenic role for autoantibodies. IVIG may react with disease-associated autoantibodies through idiotypic interactions as shown by the following lines of evidence: (1) inhibition of autoantibody activity in F(ab')2 fragments of patients' IgG by F(ab')2 fragments of IVIG; (2) retention of autoantibodies on affinity columns of Sepharose-bound F(ab')2 fragments of IVIG; and (3) recognition of the same idiotypic determinants on autoantibodies by heterologous anti-idiotypic antibodies and by IVIG. IVIG also interacts with idiotypic determinants on natural autoantibodies as indicated by the binding of monoclonal IgM secreted by Epstein-Barr virus-transformed normal human B cells to F(ab')2 fragments of IVIG and by idiotypic interactions between normal IgG antibodies within the IVIG preparations. Infusion of IVIG into patients with autoimmune diseases alters the kinetic behavior of disease-associated and natural autoantibodies of unrelated specificities. It is our view that IVIG is effective in autoimmune diseases not merely by a passive transfer of suppressive anti-idiotypes, but rather by imposing a normal function on the defective network in autoimmune patients. The intrinsic complexity of IVIG would provide a more logical (physiological) rationale for immunoregulatory therapy of autoimmune disease than idiotype-specific suppression.

Animals↗
PubMed1991

Human high molecular weight-melanoma associated antigen mimicry by an anti-idiotypic antibody: characterization of the immunogenicity and the immune response to the mouse monoclonal antibody IMel-1.

The mouse anti-idiotype (anti-id) monoclonal antibody (mAb) IMel-1 recognizes an idiotope in the antigen combining site of the immunizing anti-human high molecular weight melanoma-associated antigen (HMW-MAA) mAb 225.28. The mAb IMel-1 is able to induce an immune response against self cross-reacting HMW-MAA in rabbits that express HMW-MAA in normal tissues. Most of the rabbit anti-anti-id antibodies recognize a spatially distant determinant(s) from that defined by anti-HMW-MAA mAb 225.28. The immunogenicity of mAb IMel-1 is enhanced by its administration with the muramyl dipeptide-derived adjuvant. Anti-HMW-MAA antibodies were not detected in sera from rabbits immunized with HMW-MAA bearing cultured human melanoma cells. The differential immunogenicity of mAb IMel-1 and cell membrane bound HMW-MAA may account for the ability of anti-id mAb to induce anti-HMW-MAA immunity in patients who have not mounted such a response to HMW-MAA present in their lesions. Rabbit anti-HMW-MAA antibodies induced by anti-id mAb IMel-1 inhibited interactions of melanoma cells with elements of extracellular matrix. This may represent an additional mechanism by which anti-HMW-MAA immunity may affect the biology of melanoma cells in patients with melanoma immunized with anti-id mAb IMel-1.

Animals↗
PubMed1991

Generation and specificity of monoclonal anti-idiotypic antibodies against human HIV-specific antibodies. I. Cross-reacting idiotopes are expressed in subpopulations of HIV-infected individuals.

In this study we have generated monoclonal anti-idiotypic antibodies against human monoclonal and polyclonal anti-HIV antibodies in seropositive sera. A human anti-gp41 mAb (H2, IgM kappa) was used to immunize BALB/c mice and to prepare hybridoma anti-antibodies that react with H2 and not with normal human IgM. Similar monoclonal anti-antibodies were made in BALB/c mice immunized with Ig fraction prepared from a pool of HIV-seropositive sera. Both kinds of anti-idiotypic antibodies reacted with antibodies in pools of seropositive sera and with individual seropositive sera but not with normal human Ig or seronegative sera. The Id-positive Ig from single donors were isolated on two different anti-Id immunoabsorbents and shown to bind to p24 and gp120, respectively. The detection and isolation of idiotypically cross-reactive human anti-HIV antibodies from seropositive donors demonstrated, for the first time, the existence of shared Id expressed by antibodies against HIV Ag. The utility of cross-reacting anti-idiotypic antibodies as tools to dissect the network regulation of the anti-viral immunity in AIDS is discussed.

Animals↗