Hypersensitivity reactions to therapeutic monoclonal antibodies: phenotypes and endotypes

Publication date: Available online 5 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ghislaine Annie C Isabwe, Marlene Garcia Neuer, Leticia de las Vecillas Sanchez, Donna-Marie Lynch, Kathleen Marquis, Mariana Castells
BackgroundThe increasing use of monoclonal antibodies (mAbs) has led to a rise in hypersensitivity reactions (HSRs), which prevent their use as first-line therapy. HSRs symptoms, diagnostic tools and directed management approaches have not been standardized.ObjectiveWe propose a novel evidence-based classification of HSRs to mAbs, based on the clinical phenotypes, underlying endotypes and biomarkers; as well as their management with desensitization.MethodsPhenotypes, endotypes and biomarkers of HSRs to 16 mAbs for 104 patients were described and compared to the outcomes of 526 subcutaneous and intravenous desensitizations.ResultsInitial reactions presented with 4 patterns: Type I like reactions (63%), Cytokine-Release reactions (13%), Mixed reactions (21%) and delayed Type IV reactions (3%). In contrast, of the 23% breakthrough HSRs during desensitization, 52% were Cytokine-Release reactions, 32% were Type 1, 12% were Mixed and 4% were Type I with delayed Type IV. Skin testing to 10 mAbs in 58 patients was positive in 41% of patients. Serum tryptase was elevated in one patient and IL-6 was elevated in 8 patients during desensitization and was associated with a Cytokine-Release phenotype.ConclusionHSRs to mAbs can be defined as Type I, Cytokine-Release, Mixed (Type I/Cytokine-Release) and Type IV reactions which are identified by biomarkers such as skin test, tryptase and IL-6. These phenotypes can be used to improve personalized and precision medicine when diagnosing HSRs to mAbs and providing management recommendations with desensitization. Desensitization provides a safe and effective re-treatment option to remain on culprit mAbs as first line therapy.Clinical implicationsWe provide novel evidence-based phenotypes and endotypes of HSRs to 16 monoclonal antibodies and provide tools for diagnosis and management to improve personalized and precision medicine for HSRs to mAbs.

Graphical abstract

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