Monoclonal anti-D antibodies to prevent alloimmunization: lessons from clinical trials

Béliard, R

doi:10.1016/j.tracli.2006.03.013

Cited by 30 publications

(43 citation statements)

References 25 publications

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“…To date, only monoclonal anti-D Abs of the IgG1 and IgG3 isotype have been attempted in human AMIS experiments, based upon their ability to mediate rapid red cell clearance (11,12,26,30,43,44), as well as because of the predominance of these two isotypes after immunization with D + RBCs (44,45). 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.…”

Section: Discussionmentioning

confidence: 99%

“…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). If rapid red cell clearance is not an important or contributing attribute to an AMIS effect, then the selection of such isotypes of Abs could be detrimental.…”

Section: Discussionmentioning

confidence: 99%

“…If rapid red cell clearance is not an important or contributing attribute to an AMIS effect, then the selection of such isotypes of Abs could be detrimental. In fact, some indirect evidence suggests that red cell clearance is not strikingly related to a successful AMIS effect in some individuals (4,12,23,50,51), and work from our laboratory using SRBCs as the Ag in a murine model has shown that forcefully directing the sensitized erythrocytes to phagocytic macrophages gave rise to enhancement rather than suppression (52).…”

Section: Discussionmentioning

confidence: 99%

“…In many of these studies and others that have followed, it was noticed that the dose of anti-D that caused clearance of the D + RBCs from the circulation was related to its ability to prevent the immune response to the Ag (3,(9)(10)(11)(12). In addition, Abs reacting with the human Kell glycoprotein (a transmembrane protein distinct from RhD) were shown to inhibit the Ab response to the RhD Ag expressed on the same cell (9), cementing the concept that RBC clearance rather than epitope masking likely explains the AMIS effect with allogeneic erythrocytes.…”

mentioning

confidence: 99%

“…As a result, a mAb capable of mimicking the effects of anti-D is highly desirable (12,26,27). There have been many attempts to make monoclonal anti-D Abs, and extreme efforts have gone into choosing those Abs that give the highest rates of RBC clearance for use in clinical studies (11,(28)(29)(30).…”

mentioning

confidence: 99%

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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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