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J Allergy Clin Immunol. 2018 Jul;142(1):159-170.e2. doi: 10.1016/j.jaci.2018.02.018. Epub 2018 Mar 5.

Hypersensitivity reactions to therapeutic monoclonal antibodies: Phenotypes and endotypes.

Author information

1
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Division of Allergy and Immunology, Department of Pediatrics, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
2
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
3
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Department of Allergy, Marqués de Valdecilla University Hospital-Instituto de Investigacion Marques de Valdecilla, Santander, Spain.
4
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Electronic address: mcastells@bwh.harvard.edu.

Abstract

BACKGROUND:

The increasing use of 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.

OBJECTIVE:

We 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.

METHODS:

Phenotypes, endotypes, and biomarkers of HSRs to 16 mAbs for 104 patients were described and compared with the outcomes of 526 subcutaneous and intravenous desensitizations.

RESULTS:

Initial 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 1 patient and IL-6 was elevated in 8 patients during desensitization and was associated with a cytokine-release phenotype.

CONCLUSIONS:

HSRs 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 retreatment option to remain on culprit mAbs as first-line therapy.

KEYWORDS:

IL-6; Monoclonal antibody; biomarkers; desensitization; endotype; hypersensitivity reaction; phenotype; precision medicine; skin testing; tryptase

PMID:
29518427
DOI:
10.1016/j.jaci.2018.02.018
[Indexed for MEDLINE]

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