Anti-infliximab IgE and non-IgE antibodies and induction of infusion-related severe anaphylactic reactions.
BACKGROUND
Infliximab is a chimeric monoclonal antibody against TNF-alpha useful in the treatment of many chronic inflammatory diseases. Severe anaphylaxis has been reported during therapy, although the exact mechanism has not been fully defined. The reactions have been related to the infliximab immunogenicity and development of specific antibodies.


OBJECTIVE
Evaluation of the development of IgE and non-IgE antibodies to infliximab and their relationship with infusion reaction.


METHODS
Seventy-one patients (11 reactives, 11 therapeutically nonresponders, and 49 unreactive therapeutically responders) and 20 non-infliximab-exposed control subjects (ten rheumatoid arthritis, five spondyloarthropathies, five vasculitis) were evaluated for the presence of IgE (ImmunoCAP assay), IgM, and non-isotype-specific (ELISA assays) anti-infliximab antibodies. Sera were obtained at baseline and during the course of treatment, before each infliximab infusion.


RESULTS
Eleven out of 71 patients had a hypersensitivity reaction to infliximab. Non-isotype-specific anti-infliximab antibodies were detected in eight reactive and two nonresponder patients. Three patients with severe reactions displayed anti-infliximab IgE antibodies and positive skin testing. Detectable levels of anti-infliximab IgM antibodies were shown in three additional IgE- and skin testing-negative patients. IgE and IgM antibodies to infliximab were not detectable in the two nonresponder patients. Antibodies developed before the 2nd and the 3rd infusion, and their appearance was strictly related to the timing of the reaction.


CONCLUSIONS
This report indicates that in some patients with infliximab-related severe reactions, IgE or IgM antibodies against infliximab were detectable. The majority of reactions could be predicted by the appearance of anti-infliximab antibodies.
Vultaggio
A
A
Department of Biomedicine, Policlinico di Careggi, Florence, Italy.
Matucci
A
A
Nencini
F
F
Pratesi
S
S
Parronchi
P
P
Rossi
O
O
Romagnani
S
S
Maggi
E
E
D000328:Adult; D000707:Anaphylaxis / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012882:Skin Tests
D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D000069285:Infliximab