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Nephron 1998Data from both animal and clinical studies suggest that anti-idiotype antibodies deposited in glomeruli may be involved in the pathogenesis of glomerulonephritis. This...
Data from both animal and clinical studies suggest that anti-idiotype antibodies deposited in glomeruli may be involved in the pathogenesis of glomerulonephritis. This study was conducted to examine the role of a hybridoma-AB1-2-derived IgG anti-T15 idiotype (IgG anti-T15) in the immunopathogenesis of a short-term experimental IgA nephropathy. BALB/c mice (12/group) were administered intravenously with: (1) an equal mass (1 mg) of T15-hybridoma-derived IgA antiphosphorylcholine (PC) and PC-conjugated bovine serum albumin (BSA-PC) antigen; (2) 1 mg of IgA anti-PC, 1 mg of BSA-PC antigen, and 3 mg of IgG anti-T15, or (3) 1 mg of BSA-PC antigen alone. The mice were sacrificed 6 h after the injection. A 6-hour clearance study was performed. The initial phase of elimination of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 or those receiving the antigen alone was significantly faster than that in those receiving IgA anti-PC/BSA-PC (p < 0.001). There was no significant difference in the elimination rate of BSA-PC antigen between mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 and those receiving BSA-PC antigen alone. The late phases of elimination of the BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 showed somewhat similar to those of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC. Moreover, mice injected with IgA anti-PC/BSA-PC/IgG anti-T15 showed a significantly less glomerular BSA-PC antigen deposition than those injected with IgA anti-PC/BSA-PC (positive control), as demonstrated by light microscopy, autoradiography, and immunohistochemistry (each p < 0.001). It is inferred that the injected IgG anti-T15 could react with the IgA anti-PC in vivo, directly interfering with immune complex formation by the IgA anti-PC and BSA-PC antigen, thereby resulting in diminished glomerular deposition of the BSA-PC antigen. These findings suggest that an anti-idiotype antibody may be protective in the immunopathogenesis of IgA nephropathy, because of its inhibitory effect on glomerular trapping of an antigen.
Topics: Animals; Antibodies, Anti-Idiotypic; Antigen-Antibody Complex; Antigens; Female; Glomerular Mesangium; Glomerulonephritis, IGA; Immunoglobulin A; Kidney; Mice; Mice, Inbred BALB C; Phosphorylcholine; Serum Albumin, Bovine
PubMed: 9578073
DOI: 10.1159/000044976 -
Preparative Biochemistry & Biotechnology 2020Immunoassay has been widely used in the screening of mycotoxins, which may be hazardous to the operator or the environment. This study was to develop a green way to...
Immunoassay has been widely used in the screening of mycotoxins, which may be hazardous to the operator or the environment. This study was to develop a green way to measure zearalenone (ZEN) with a monoclonal β-type anti-idiotype antibody (Ab2β) against ZEN in place of ZEN standard. Six monoclonal β-type anti-idiotype antibodies were prepared. The 50% inhibitory concentration (IC) value to ZEN of the six antibodies was between 34.45 ± 1.12-182.12 ± 15.40 nM. A green ELISA was then developed and validated. The quantitative conversion formula between ZEN and the monoclonal Ab2β against ZEN was = 0.092, = 0.990. The working range was 2.63-100.64 ng ml. The recovery rate in spiked feed samples was from 82.15% to 102.79%, and the within-assay and between-assay coefficient variation (CV) level were less than 10.00%. A good correlation was obtained by high-performance liquid chromatography method (HPLC) to validate the developed method.
Topics: Animal Feed; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Enzyme-Linked Immunosorbent Assay; Food Contamination; Green Chemistry Technology; Limit of Detection; Mycotoxins; Zearalenone
PubMed: 31876440
DOI: 10.1080/10826068.2019.1703195 -
Blood Jun 2009Previous studies demonstrated that vaccination-induced tumor-specific immune response is associated with superior clinical outcome in patients with follicular lymphoma....
Previous studies demonstrated that vaccination-induced tumor-specific immune response is associated with superior clinical outcome in patients with follicular lymphoma. Here, we investigated whether this positive correlation extends to overall survival (OS). We analyzed 91 untreated patients who received CVP chemotherapy (cyclophosphamide, vincristine, and prednisone) followed by idiotype vaccination. Idiotype proteins were produced either by the hybridoma method or by expression of recombinant idiotype-encoding sequences in mammalian or plant-based expression systems. We found that achieving a complete response/complete response unconfirmed (CR/CRu) to CVP and making an anti-idiotype antibody are 2 independent factors that each correlated with longer OS at 10 years (89% vs 68% with or without a CR/CRu, P = .024; 90% vs 69% with or without tumor-specific antibody production; P = .027). In the subset of patients who received hybridoma-generated vaccines, we found that anti-idiotype production was even more highly associated with superior OS (P < .002); this was the case even in patients with a partial response (PR) to CVP (P < .001).
Topics: Antibodies, Anti-Idiotypic; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Follow-Up Studies; Humans; Immunotherapy; Lymphoma, Follicular; Prednisone; Survival Rate; Treatment Outcome; Vaccination; Vincristine
PubMed: 19346494
DOI: 10.1182/blood-2009-01-201988 -
Cellular Immunology May 1983The present report demonstrates that cells expressing idiotypic determinants on their surfaces can be specifically destroyed by anti-idiotypic antibodies acting as...
The present report demonstrates that cells expressing idiotypic determinants on their surfaces can be specifically destroyed by anti-idiotypic antibodies acting as inducers of antibody-dependent cell-mediated cytotoxicity. Lysis of surface-idiotype-positive hybridoma cells was effected by mouse spleen cells, mouse peritoneal cells, or human blood mononuclear cells, in the presence of anti-idiotypic antibodies. In order for lysis to occur, the simultaneous presence of Fc receptor-bearing cytotoxic cells and anti-idiotypic antibodies was required. Specificity of lysis was conferred by the anti-idiotypic antibody. Hybridoma cells expressing a different idiotype could not be lysed. Anti-idiotypic antibody-dependent cell-mediated cytotoxicity against 51Cr-labeled cells expressing a particular idiotype could be induced by the specific anti-idiotypic antibodies and inhibited by unlabeled idiotype-positive cells or by idiotype in a soluble form. Cytotoxicity could not be inhibited by the presence of bystander cells or monoclonal antibodies expressing a different idiotype. It is proposed that ADCC lysis of idiotype-positive cells has important implications for understanding the regulation of immune responses by an idiotype-anti-idiotype network. This cytolytic pathway provides an extremely specific and effective mode of control of idiotype-positive cells by anti-idiotype antibody. Previous observations that an intact Fc fragment was necessary for anti-idiotype antibodies to exert suppressive effects in vivo further support this hypothesis.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibody Specificity; Antibody-Dependent Cell Cytotoxicity; Cell Line; Female; Humans; Hybridomas; Immunoglobulin Idiotypes; Male; Mice; Mice, Inbred A; Mice, Inbred BALB C
PubMed: 6602001
DOI: 10.1016/0008-8749(83)90256-3 -
Journal of Clinical & Laboratory... May 1988Anti-idiotype antibodies (Anti-Id Ab) are believed to normally exert a form of feedback control on Ab production. An abnormality in this network might lead to excess Ab...
Anti-idiotype antibodies (Anti-Id Ab) are believed to normally exert a form of feedback control on Ab production. An abnormality in this network might lead to excess Ab production. To detect the abnormalities in immunoregulation in autoimmune thyroid disease, we tried to demonstrate anti-Id Ab to anti-thyroglobulin antibody (ATA) and to correlate them to the clinical course of disease. We developed two assays, one based on the binding of anti-Id Ab to ATA (Id) and a second on the inhibitory activity of anti-Id Ab in the reaction of human thyroglobulin (hTG) and ATA. We could not demonstrate anti-Id Ab in either assay. Possibly anti-Id Ab to ATA is not formed sufficiently to be detected in our assays, or is only present in specific phases of the course of autoimmune thyroid disease. During studies of anti-Id Ab we found "pepsin site" Ab in patients and normal subjects. We developed a new solid phase radioimmune assay for this Ab, an antibody which reacts with antigens exposed on IgG when F(ab')2 fragments of IgG are prepared. The incidence of this Ab did not differ between patients and normal subjects. IgG from patients with autoimmune thyroid disease which contained high levels of anti-pepsin site Ab, did not show any specificity for ATA (Id), nor did it inhibit the reaction between hTG (Ag) and ATA (Id). The importance of this anti-F(ab')2 antibody remains to be determined, but it does not represent an anti-Id Ab.
Topics: Antibodies, Anti-Idiotypic; Autoantibodies; Autoimmune Diseases; Graves Disease; Humans; Immunoglobulin Fab Fragments; Immunoglobulin Idiotypes; Pepsin A; Radioimmunoassay; Thyroiditis, Autoimmune
PubMed: 3141624
DOI: No ID Found -
PloS One 2014Pre-clinical and clinical studies of therapeutic antibodies require highly specific reagents to examine their immune responses, bio-distributions, immunogenicity, and...
Pre-clinical and clinical studies of therapeutic antibodies require highly specific reagents to examine their immune responses, bio-distributions, immunogenicity, and pharmacodynamics in patients. Selective antigen-mimicking anti-idiotype antibody facilitates the assessment of therapeutic antibody in the detection, quantitation and characterization of antibody immune responses. Using mouse specific degenerate primer pairs and splenocytic RNA, we generated an idiotype antibody-immunized phage-displayed scFv library in which an anti-idiotype antibody against the therapeutic chimera anti-CD22 antibody SM03 was isolated. The anti-idiotype scFv recognized the idiotype of anti-CD22 antibody and inhibited binding of SM03 to CD22 on Raji cell surface. The anti-idiotype scFv was subsequently classified as Ab2γ type. Moreover, our results also demonstrated firstly that the anti-idiotype scFv could be used for pharmacokinetic measurement of circulating residual antibody in lymphoma patients treated with chimera anti-CD22 monoclonal antibody SM03. Of important, the present approach could be easily adopted to generate anti-idiotype antibodies for therapeutic antibodies targeting membrane proteins, saving the cost and time for producing a soluble antigen.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibody Specificity; Cell Line, Tumor; Female; Lymphoma; Mice; Recombinant Fusion Proteins; Sialic Acid Binding Ig-like Lectin 2; Single-Chain Antibodies
PubMed: 24816427
DOI: 10.1371/journal.pone.0096697 -
Autoimmunity Reviews Jul 2010A common serologic finding in autoimmune diseases is the presence of autoantibodies against intracellular autoantigens. Recent data suggest that an anti-idiotypic... (Review)
Review
A common serologic finding in autoimmune diseases is the presence of autoantibodies against intracellular autoantigens. Recent data suggest that an anti-idiotypic network exists in these diseases, regulating the production of autoantibodies (idiotypic response). The anti-idiotypic antibodies can be monitored using complementary epitopes, designed according to the “molecular recognition” theory. The role of antiidiotypic antibodies in neonatal lupus and type 1 diabetes are discussed. In neonatal lupus, mothers with high anti-idiotypic antibody activity against anti-La autoantibodies are at lower risk of giving birth to an un-healthy child, as compared with mothers without anti-idiotypic antibodies. Similarly,the lack of particular anti-idiotypic antibodies against anti-GAD65 autoantibodies predispose in type 1 diabetes. These findings imply that antiidiotypic antibodies may confer protection from the harmful effect of autoantibodies in certain autoimmune diseases [corrected].
Topics: Antibodies, Anti-Idiotypic; Autoantibodies; Autoantigens; Autoimmune Diseases; Diabetes Mellitus, Type 1; Epitopes; Humans; Immunoglobulin Idiotypes; Lupus Erythematosus, Systemic
PubMed: 20478412
DOI: 10.1016/j.autrev.2010.05.013 -
MAbs 2020Antibody formation to human(ized) therapeutic antibodies in humans is highly skewed toward anti-idiotype responses, probably because the idiotype is the only 'foreign'...
Antibody formation to human(ized) therapeutic antibodies in humans is highly skewed toward anti-idiotype responses, probably because the idiotype is the only 'foreign' part of the antibody molecule. Here, we analyzed antibody responses to F(ab')2 fragments of a panel of 17 human(ized) therapeutic antibodies in rabbits. Homology between the rabbit germline and the human(ized) antibodies is moderate not only for the variable domains (both the complementarity-determining regions and the framework regions), but also for the constant domains (66% or less). Nevertheless, we observed a highly skewed anti-idiotype response in all cases, with up to >90% of the antibodies directed toward the idiotype. These results indicate that the idiotype may be inherently immunodominant. We used these biased responses to raise monoclonal rabbit anti-idiotype antibodies against secukinumab, ustekinumab, reslizumab, mepolizumab, palivizumab, and dupilumab and demonstrate the potential to develop sensitive pharmacokinetic assays with these antibodies.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibody Formation; Humans; Immunization; Immunoglobulin Fab Fragments; Rabbits
PubMed: 32887534
DOI: 10.1080/19420862.2020.1814661 -
Journal of Immunological Methods Mar 2003Anti-idiotype antibodies recognizing the variable regions of a particular anti-hapten antibody are valuable tools, which can be used in sensitive hapten immunoassays...
Monoclonal anti-idiotype antibodies recognizing the variable region of a high-affinity antibody against 11-deoxycortisol. Production, characterization and application to a sensitive noncompetitive immunoassay.
Anti-idiotype antibodies recognizing the variable regions of a particular anti-hapten antibody are valuable tools, which can be used in sensitive hapten immunoassays based on a noncompetitive format. Here, we describe the production and characterization of monoclonal anti-idiotype antibodies against idiotopes on the variable regions of an antibody showing high affinity and specificity to 11-deoxycortisol (11-DC). 11-DC is the biosynthetic precursor of cortisol and a diagnostic index for the assessment of pituitary-adrenal function. BALB/c or A/J mice were repeatedly immunized with the anti-11-DC antibody conjugated with keyhole limpet hemocyanin and their spleen cells were then fused with P3/NS1/1-Ag4-1 myeloma cells. Seven kinds of anti-idiotype antibodies were generated, one of which was a beta-type antibody recognizing the paratope and others which were alpha-type antibodies recognizing the framework region. A noncompetitive ELISA based on idiotype-anti-idiotype reactions was established using one of these alpha-type antibodies in combination with the beta-type antibody and with the anti-11-DC antibody. This noncompetitive assay system provided improved sensitivity (detection limit: 1.0 pg=2.9 fmol), which is approximately 10 times higher than the corresponding competitive enzyme immunoassay, and offered a practical specificity for clinical use. Appropriate serum 11-DC levels were obtained for normal subjects [0.16+/-0.09 (S.D.) microg/l (n=6), ranging from 0.086 to 0.316 microg/l] using the present assay system.
Topics: Animals; Antibodies; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibody Affinity; Antibody Specificity; Cortodoxone; Enzyme-Linked Immunosorbent Assay; Female; Haptens; Humans; Immunoglobulin Variable Region; Mice; Mice, Inbred BALB C; Sensitivity and Specificity
PubMed: 12609533
DOI: 10.1016/s0022-1759(02)00501-x -
Progress in Clinical and Biological... 1980Anti-IgGb2a allotype antibodies produced by various responder strains of mice expressed a cross-reactive idiotype. This cross-reactive idiotype was evidenced with BAB.... (Review)
Review
Anti-allotype antibody response in mice: expression of a cross-reactive idiotype and its regulation by auto-anti-idiotypic antibodies in maternally allotype suppressed F1 hybrids.
Anti-IgGb2a allotype antibodies produced by various responder strains of mice expressed a cross-reactive idiotype. This cross-reactive idiotype was evidenced with BAB. 14 and CXBI anti-idiotypic sera raised following immunization with affinity chromatography purified BALB/c anti-CBPC 101 (IgGb2a) antibodies originating from a single BALB/c mouse. F1 hybrids of BALB/c X C.B20 parents, which have been maternally suppressed for IgGb2a allotype as a result of immunization with CBPC 101, produced anti-allotype antibodies lacking cross-reactive idiotype. Furthermore, these mice produced auto-antibodies directed at the IdX of anti-IgGb2a allotypic antibodies.
Topics: Animals; Antibodies, Anti-Idiotypic; Autoantibodies; Cross Reactions; Female; Hybrid Cells; Immunoglobulin Idiotypes; Male; Mice
PubMed: 6994111
DOI: No ID Found