Anaphylactic shock caused by immunoglobulin E sensitization after retreatment with the chimeric anti-interleukin-2 receptor monoclonal antibody basiliximab

Transplantation. 2003 Aug 15;76(3):459-63. doi: 10.1097/01.TP.0000073809.65502.8F.

Abstract

Background: Repeated administration of chimeric or humanized monoclonal antibodies is generally well tolerated. Anti-idiotypic sensitization is rare and is considered to be of no clinical significance. We observed a child who experienced anaphylactic shock when he received a second course of basiliximab at the time of his second renal transplantation. We therefore searched for the presence of anti-basiliximab immunoglobulin (Ig) E in this patient.

Methods: Serum levels of anti-basiliximab IgE, assay of the anti-murine reactivity of circulating anti-basiliximab IgE, and assays for serum anti-mouse antibodies and global anti-basiliximab anti-idiotypic antibodies were carried out by enzyme-linked immunosorbent assay. Anti-basiliximab IgE antibodies on circulating basophils were evaluated by the ability of the patient's blood to produce leukotrienes in vitro after exposure to basiliximab.

Results: Sequential assays of serum samples by enzyme-linked immunosorbent assay indicated that anti-basiliximab IgE antibodies appeared after the second basiliximab course. There was no IgE reactivity toward a control murine IgG2a monoclonal antibody (mAb), indicating that the IgE response was directed exclusively against basiliximab idiotypes. There was no IgE reactivity against the humanized anti-interleukin-2 receptor mAb daclizumab, which was derived from a distinct parental murine mAb. Patient basophils harvested months after the anaphylactic shock produced leukotrienes in vitro on exposure to basiliximab.

Conclusions: Patients exposed to chimeric antibodies may develop an anti-idiotypic IgE response that can trigger anaphylactic shock on further exposure. Specific anti-idiotypic IgE may be bound to basophils even in the absence of circulating IgE.

Publication types

  • Case Reports

MeSH terms

  • Anaphylaxis / etiology*
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal, Humanized
  • Basiliximab
  • Basophils / immunology
  • Child, Preschool
  • Cross Reactions
  • Daclizumab
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunization
  • Immunoglobulin E / analysis*
  • Immunoglobulin G / immunology
  • Immunoglobulin Idiotypes / immunology
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / immunology*
  • Male
  • Receptors, Interleukin-2 / immunology*
  • Recombinant Fusion Proteins*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Immunoglobulin Idiotypes
  • Immunosuppressive Agents
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • Immunoglobulin E
  • Basiliximab
  • Daclizumab