Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 142 (1), 159-170.e2

Hypersensitivity Reactions to Therapeutic Monoclonal Antibodies: Phenotypes and Endotypes


Hypersensitivity Reactions to Therapeutic Monoclonal Antibodies: Phenotypes and Endotypes

Ghislaine Annie C Isabwe et al. J Allergy Clin Immunol.


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.

Similar articles

See all similar articles

Cited by 3 PubMed Central articles

  • The Importance of Early Identification of Infusion-Related Reactions to Monoclonal Antibodies
    MC Cáceres et al. Ther Clin Risk Manag 15, 965-977. PMID 31447561.
    Monoclonal antibodies constitute important and useful tools in clinical practice and biotechnology for diagnosing and treating infectious, inflammatory, immunological and …
  • Pediatric Drug Hypersensitivity
    CRF Rukasin et al. Curr Allergy Asthma Rep 19 (2), 11. PMID 30793223. - Review
    This paper will discuss the safety and use of risk stratification to proceed directly to oral challenge without prior skin testing for β-lactam reactions. We review uniqu …
  • Immunogenicity of Protein Pharmaceuticals
    R Dingman et al. J Pharm Sci 108 (5), 1637-1654. PMID 30599169. - Review
    Protein therapeutics have drastically changed the landscape of treatment for many diseases by providing a regimen that is highly specific and lacks many off-target toxici …

Publication types