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IgG4 anti‐infliximab in treated patients: Clinical impact and temporal evolution
Author(s) -
Vultaggio A.,
Nencini F.,
Carraresi A.,
Pratesi S.,
Movérare R.,
Eriksson C.,
Venemalm L.,
Maggi E.,
Matucci A.
Publication year - 2018
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13471
Subject(s) - medicine , infliximab , antibody , cohort , immunoglobulin e , gastroenterology , immunology , tumor necrosis factor alpha
Background Infliximab (IFX) carries potential risk of immunogenicity with the production of anti‐drug antibodies (ADA). ADA may belong to different isotypes and are usually measured by ELISA bridging assay. This test is not designed to detect IgG4 antibodies. The aim was to measure IgG4 anti‐IFX antibodies in a cohort of IFX‐treated patients and to evaluate their relationship with ADA and their clinical impact. Methods Anti‐drug antibodies were detected using a bridging ELISA in the serum of 222 treated patients with different clinical outcomes to IFX. The same samples were analyzed for IgG4 anti‐IFX antibodies using an experimental ImmunoCAP assay with reduced serum IgG4 background levels. A longitudinal evaluation was performed in a subgroup of 38 patients to define the temporal evolution of IgG4 anti‐IFX. Results IgG4 anti‐IFX was found in 26.6% of patients. Eighty of 222 patients were ADA+ (36%) and the majority (57/80, 71.3%) had IgG4 anti‐IFX. Two IgG4‐positive but ADA‐negative patients were identified. IgG4 anti‐IFX levels correlated with the serum levels of ADA. IgG4 anti‐IFX was more common in both reactive and nonresponder patients than in tolerant/responder patients. Patients who had experienced IgE‐mediated reactions displayed significantly higher IgG4 anti‐IFX than IgE‐negative reactive patients. The majority of patients tested positive for IgG4 anti‐IFX after the first seven infusions. Conclusions IgG4 anti‐IFX is common in treated patients and a large part of ADA producing patients produce IgG4 antibodies. The IgG4 anti‐IFX response does not prevent hypersensitivity reactions to IFX and correlates with the IgE anti‐IFX response.