Anaphylactic shock caused by immunoglobulin E sensitization after retreatment with the chimeric anti-interleukin-2 receptor monoclonal antibody basiliximab.
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.
Baudouin
Véronique
V
Department of Nephrology, Hopital Robert Debré, Paris, France.
Crusiaux
Alain
A
Haddad
Elie
E
Schandene
Liliane
L
Goldman
Michel
M
Loirat
Chantal
C
Abramowicz
Daniel
D
D000707:Anaphylaxis / Q000209:etiology*; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized; D000077552:Basiliximab; D001491:Basophils / Q000276:immunology; D002675:Child, Preschool; D003429:Cross Reactions; D000077561:Daclizumab; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000032:analysis*; D007074:Immunoglobulin G / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011993:Recombinant Fusion Proteins
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E; D000077552:Basiliximab; D000077561:Daclizumab