The IgE humoral response in OKT3-treated patients. Incidence and fine specificity.
We recently described a case of anaphylaxis occurring at the time of retreatment with OKT3 of a renal allograft recipient in whom, for the first time, high anti-OKT3 IgE levels were documented. This led us to examine a large series of sera from 181 OKT3-treated patients to better define the frequency of IgE sensitization, its fine specificity (anti-isotypic and/or anti-idiotypic) and its relation to the appearance of IgG anti-OKT3 antibodies (Abs). Six patients out of the 181 assayed have developed anti-OKT3 IgE Abs as detected by ELISA. The earliest time of appearance of IgE anti-OKT3 Abs was 10 days after starting OKT3 (range, 10-25). The IgE response peaked by day 18 (range, 11-35) and had usually disappeared at 3 months after treatment. A more careful dissection of the fine specificity of the IgE response revealed that three of the four patients tested had developed an exclusive anti-idiotypic response. In the last patient, an anti-isotypic component was present since anti-OKT3 IgE Abs also reacted with control IgG2a, IgG2b, and IgG3 monoclonal antibodies. Importantly, anti-OKT3 IgE Abs were only detected in heavily sensitized patients also showing high titers of IgG specific Abs by ELISA (> or = 1/1000) as well as "blocking" anti-OKT3 antibodies, as assessed by immunofluorescence. We conclude that (1) exposure to OKT3 may lead to specific IgE sensitization that, however, only appears in about 38% of the patients; (2) IgE Abs mostly appear in patients also showing high levels of conventional IgG anti-OKT3 Abs including the presence of "blocking" anti-idiotypic Abs, and (3) IgE Abs may be directed to both idiotypic and isotypic determinants of the monoclonal antibody.
Abramowicz
D
D
Department of Nephrology, Hopital Erasme, Brussels, Belgium.
Crusiaux
A
A
Niaudet
P
P
Kreis
H
H
Chatenoud
L
L
Goldman
M
M
D000818:Animals; D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D001667:Binding, Competitive; D000939:Epitopes; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D007700:Kinetics; D051379:Mice; D016853:Muromonab-CD3 / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*
D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D000939:Epitopes; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; C026408:anti-IgE antibodies; C048844:anti-IgG; D007073:Immunoglobulin E