Antibody‐Mediated Immune Suppression to the Rh Factor: Animal Models Suggesting Mechanism of Action

Pollack, William; Gorman, J.M.; Hager, Henrik; Freda, Vincent J.; Tripodi, D

doi:10.1111/j.1537-2995.1968.tb04891.x

Cited by 84 publications

(37 citation statements)

References 35 publications

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“…Studies performed in the 1960s using polyclonal anti-D showed that suboptimal doses can sometimes cause a small amount of immune enhancement (2,3), and this has been seen with some monoclonal anti-D Abs (23,50). In addition, some anti-D mAbs did not adequately prevent the immune response, although they induced rapid RBC clearance (12,23,50).…”

Section: Discussionmentioning

confidence: 99%

“…The Ab response to RBCs can be downregulated by the simultaneous administration of an RBC-specific Ab concurrent with exposure to the foreign red cell (1)(2)(3)(4). This effect has been termed Ab-mediated immune suppression (AMIS), and AMIS has been observed with a variety of different cell types, including platelets, leukocytes, microbes, and particulate Ags, such as vaccines in different mammals (5)(6)(7)(8).…”

mentioning

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.…”

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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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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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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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“…12,23,32 To model this effect of IgG, mice were transfused with SRBCs or with SRBC + anti-SRBC IgG (AMIS). An SRBC-specific IgM response was clearly detected in the SRBC-treated mice whereas this response was significantly reduced under AMIS conditions (P < 0Á001) ( Fig.…”

Section: Amis Attenuates the Initial Antigen Challenge But Not Subseqmentioning

confidence: 99%

“…5,19 This inhibitory effect of IgG has been formally described as antibody-mediated immune suppression (AMIS), a name which itself implies a suppressive event. 5,11,[20][21][22][23][24][25][26][27][28][29] Suppression of B-cell activation has been suggested to involve regulatory T cells 30 or immune suppressive cytokines such as TGF-b. 5,31 In this work, we have examined whether suppression or clonal deletion can be observed under AMIS conditions by testing the ability of the immune system to respond to RBCs during or after the induction of AMIS.…”

Section: Introductionmentioning

confidence: 99%

Immunoglobulin G‐mediated regulation of the murine immune response to transfused red blood cells occurs in the absence of active immune suppression: implications for the mechanism of action of anti‐D in the prevention of haemolytic disease of the fetus and newborn?

et al. 2008

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SummaryAnti-D has been widely and effectively used in Rhesus blood group D negative mothers for the prevention of haemolytic disease of the fetus and newborn; its mechanism of action however, often referred to as antibody-mediated immune suppression (AMIS), remains largely unresolved. We investigated, in a murine model, whether active immune suppression or clonal deletion mediated by anti-red blood cell (RBC) immunoglobulin G (IgG) could explain the phenomenon of AMIS. Transfusion of IgG-opsonized foreign RBCs (i.e. AMIS) strongly attenuated antibody responses compared to transfusion of untreated foreign RBCs. When the AMIS-mice were subsequently transfused with untreated RBCs, no immune suppression was observed at 5 and 35 days after AMIS induction; in fact, the mice responded to retransfusion with untreated RBCs in a manner that was characteristic of a secondary immune response. When IgG-opsonized RBCs were transfused concurrently with untreated RBCs, a dose-dependent reduction of the antibody response was observed. This work suggests that the attenuation of the antibody responsiveness by anti-RBC IgG is not associated with active immune suppression or clonal deletion at either the T-cell or B-cell level; rather, the effect appears more characteristic of B-cell unresponsiveness to IgG-opsonized RBCs. These results may have implications for the understanding of the mechanism of action of anti-D in haemolytic disease of the fetus and newborn.

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Rho (D) Immune Globulin (Human)

Ascari¹

1968

JAMA

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Antibody‐Mediated Immune Suppression to the Rh Factor: Animal Models Suggesting Mechanism of Action

Cited by 84 publications

References 35 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

Immunoglobulin G‐mediated regulation of the murine immune response to transfused red blood cells occurs in the absence of active immune suppression: implications for the mechanism of action of anti‐D in the prevention of haemolytic disease of the fetus and newborn?

Rho (D) Immune Globulin (Human)

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