Blocking function of allergen-specific immunoglobulin G, F(ab')2, and Fab antibodies prepared from patients undergoing Dermatophagoides pteronyssinus immunotherapy

Ann Allergy Asthma Immunol. 2022 Jun;128(6):689-696. doi: 10.1016/j.anai.2022.03.031. Epub 2022 Apr 8.

Abstract

Background: The blocking function of allergen-specific F(ab')2 [sF(ab')2] and Fab (sFab) fragment antibodies prepared from allergen immunotherapy-induced specific immunoglobulin G (sIgG) has not been fully investigated.

Objective: To investigate the inhibitory function of sIgG, sF(ab')2, and sFab antibodies in patients undergoing Dermatophagoides pteronyssinus (Der-p) subcutaneous immunotherapy (SCIT).

Methods: This study involved 10 subjects (aged 18-42 years) with house dust mite allergic rhinitis or asthma who received a 156-week course of Der-p SCIT. Total IgG levels were purified from the serum of the participants at weeks 0 and 156 by protein A affinity chromatography. Der-p sIgG was purified by affinity chromatography with Der-p as a ligand at week 156. The sF(ab')2 and sFab antibodies were prepared from Der-p sIgG by treatment with pepsin and papain, respectively. Furthermore, IgE-facilitated allergen binding assay, basophil activation inhibition test, and cytokine release inhibition assay were used to assess the inhibitory function of Der-p sIgG, sF(ab')2, and sFab antibodies.

Results: We found that the Der-p sIgG, sF(ab')2, and sFab antibodies markedly blocked Der-p-allergen sIgE complex binding to B cells, inhibited basophil activation, and markedly reduced the production of interleukin (IL)-5, IL-13, IL-17, and tumor necrosis factor-α by peripheral blood mononuclear cells.

Conclusion: SCIT-induced Der-p sIgG, sF(ab')2, and sFab antibodies may block the formation of Der-p-sIgE complexes and may serve as a potential allergen-targeted biologics candidate for the treatment of allergic asthma.

Clinical trial registration: This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University and registered in the Chinese Clinical Trial Registry (ChiCTR-OOC-15006207, https://www.chictr.org.cn/enindex.aspx).

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Animals
  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Asthma* / therapy
  • Dermatophagoides pteronyssinus
  • Desensitization, Immunologic / methods
  • Humans
  • Immunoglobulin E
  • Immunoglobulin G
  • Immunologic Factors
  • Leukocytes, Mononuclear / metabolism
  • Rhinitis, Allergic, Perennial*

Substances

  • Allergens
  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Immunoglobulin G
  • Immunologic Factors
  • Immunoglobulin E

Associated data

  • ChiCTR/ChiCTR-OOC-15006207