Section 1C: Assessment of the functional activity and IgG Fc receptor utilisation of 64 IgG Rh monoclonal antibodies. Coordinator’s report

Kumpel, Belinda M.; Béliard, R; Brossard, Y.; Edelman, L; Haas, Masja de; Jackson, Dave; Kooyman, P; Ligthart, Peter; Monchatre, Elizabeth; Overbeeke, M. A. M.; Puillandre, Philippe; Romeuf, Christophe de; Wilkes, Anthony M.

doi:10.1016/s1246-7820(01)00215-4

Cited by 23 publications

(36 citation statements)

References 15 publications

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“…Other isotypes of anti-D have also been detected (11,(44)(45)(46)(47)(48), and it is not yet clear which anti-D Abs actually mediate AMIS effects versus some that could be disadvantageous. In human clinical trials, some IgG1/3 mAbs were shown to mediate an enhanced immune response to the D Ag, whereas others mediated AMIS effects almost as well as polyclonal anti-D (12,23,30,49,50).…”

Section: Discussionmentioning

confidence: 99%

Antibody-Mediated Immune Suppression of Erythrocyte Alloimmunization Can Occur Independently from Red Cell Clearance or Epitope Masking in a Murine Model

Stowell

Bernardo

et al. 2014

The Journal of Immunology

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Anti-D can prevent immunization to the RhD Ag on RBCs, a phenomenon commonly termed Ab-mediated immune suppression (AMIS). The most accepted theory to explain this effect has been the rapid clearance of RBCs. In mouse models using SRBC, these xenogeneic cells are always rapidly cleared even without Ab, and involvement of epitope masking of the SRBC Ags by the AMIS-inducing Ab (anti-SRBC) has been suggested. To address these hypotheses, we immunized mice with murine transgenic RBCs expressing the HOD Ag (hen egg lysozyme [HEL], in sequence with ovalbumin, and the human Duffy transmembrane protein) in the presence of polyclonal Abs or mAbs to the HOD molecule. The isotype, specificity, and ability to induce AMIS of these Abs were compared with accelerated clearance as well as steric hindrance of the HOD Ag. Mice made IgM and IgG reactive with the HEL portion of the molecule only. All six of the mAbs could inhibit the response. The HEL-specific Abs (4B7, IgG1; GD7, IgG2b; 2F4, IgG1) did not accelerate clearance of the HOD-RBCs and displayed partial epitope masking. The Duffy-specific Abs (MIMA 29, IgG2a; CBC-512, IgG1; K6, IgG1) all caused rapid clearance of HOD RBCs without steric hindrance. To our knowledge, this is the first demonstration of AMIS to erythrocytes in an all-murine model and shows that AMIS can occur in the absence of RBC clearance or epitope masking. The AMIS effect was also independent of IgG isotype and epitope specificity of the AMIS-inducing Ab.

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Section: Discussionmentioning

confidence: 99%

Antibody-Mediated Immune Suppression of Erythrocyte Alloimmunization Can Occur Independently from Red Cell Clearance or Epitope Masking in a Murine Model

Stowell

Bernardo

et al. 2014

The Journal of Immunology

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“…The D antigen is a 32-kD erythrocyte (red blood cell [RBC]) protein encoded by the RHD gene, which has several allelic variants that can generate different epitopes; this allows the production of many MoAnti-D. [6][7][8][9][10][11][12][13] Hundreds of MoAnti-D have been produced for phenotypic studies, and many have been characterized for their ability to inhibit physiologic processes in models of HDN. [9][10][11][12][13] With respect to AITP, however, only one study attempted to treat patients with AITP with MoAnti-D, but platelet counts were not increased.…”

Section: Introductionmentioning

confidence: 99%

Epitope specificity and isotype of monoclonal anti-D antibodies dictate their ability to inhibit phagocytosis of opsonized platelets

Kjaersgaard

Aslam

Kim³

et al. 2007

Blood

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Rh immune globulin (WinRho SDF; Cangene, Mississauga, ON, Canada) is an effective treatment for autoimmune thrombocytopenic purpura; however, maintaining a sustained supply for its use in autoimmune thrombocytopenic purpura and its primary indication, hemolytic disease of the newborn, makes the development of alternative reagents desirable. We compared Rh immune globulin and 6 human monoclonal anti-D antibodies (MoAnti-D) with differing isotypes and specificities for their ability to opsonize erythrocytes and inhibit platelet phagocytosis in an in vitro assay. Results demonstrated that opsonization of erythrocytes with Rh immune globulin significantly (P < .001) reduced phagocytosis of fluorescently labeled opsonized platelets in an Fcdependent manner. Of the MoAnti-D that shared specificity but differed in isotype, only IgG3 antibodies could significantly (P < .001) inhibit platelet phagocytosis. In contrast, 2 MoAnti-D shared isotypes and differed in specificity; however, only one could significantly (P < .001) inhibit platelet phagocytosis. The results suggest that MoAnti-D epitope specificity and isotypes are critical requirements for optimal inhibition of opsonized platelet phagocytosis.

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“…1b). Antibody interactions with different types of FcγR can be studied using blocking antibodies against corresponding receptors (Kumpel et al, 2002a). Sometimes researchers apply a modification of the test, the so-called K-ADCC, which is designed to evaluate the interaction of antibodies with FcγRIIIA only.…”

Section: Fcγ Receptors and Assays For Evaluation Of The Functional Prmentioning

confidence: 99%

“…In contrast, only a few monoclonals have this property, which was demonstrated, for example, by a study of the functional activity of monoclonal anti-D IgGs submitted to the Fourth International Workshop on Monoclonal Antibodies against Human Red Blood Cells (Kumpel et al, 2002a). Only 8 out of 64 anti-D were shown to be able to mediate hemolysis in ADCC in the presence of monomeric IgG (ADCC+IG, Fig.…”

Section: Characteristic Features Of Poly-and Monoclonal Antibodies Inmentioning

confidence: 99%

Anti-RhD-Mediated Immunosuppression: Can Monoclonal Antibodies Imitate the Action of Polyclonal Antibodies?

Оловникова¹

2012

Immunosuppression - Role in Health and Diseases

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Section 1C: Assessment of the functional activity and IgG Fc receptor utilisation of 64 IgG Rh monoclonal antibodies. Coordinator’s report

Cited by 23 publications

References 15 publications

Antibody-Mediated Immune Suppression of Erythrocyte Alloimmunization Can Occur Independently from Red Cell Clearance or Epitope Masking in a Murine Model

Antibody-Mediated Immune Suppression of Erythrocyte Alloimmunization Can Occur Independently from Red Cell Clearance or Epitope Masking in a Murine Model

Epitope specificity and isotype of monoclonal anti-D antibodies dictate their ability to inhibit phagocytosis of opsonized platelets

Anti-RhD-Mediated Immunosuppression: Can Monoclonal Antibodies Imitate the Action of Polyclonal Antibodies?

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