Yonsei Med J.  2016 Nov;57(6):1427-1434. 10.3349/ymj.2016.57.6.1427.

Different Responses in Induction of Allergen Specific Immunoglobulin G4 and IgE-Blocking Factors for Three Mite Subcutaneous Immunotherapy Products

• Park KH
• Lee SC
• Son YW
• Jeong KY
• Shin YS
• Shin JU
• Sim DW
• Park HJ
• Lee JH
• Lee KH
• Park JW

• KMID: 2427161
• DOI: http://doi.org/10.3349/ymj.2016.57.6.1427

Abstract

PURPOSE
Specific immunoglobulin G4 (sIgG4) and immunoglobulin E (IgE)-blocking factors produced by subcutaneous immunotherapy (SCIT) play a critical role in the induction of allergen tolerance. However, comparative studies of available SCIT reagents on the induction of sIgG4 are limited. We compared increases in sIgG4 for three different house dust mite (HDM) SCIT reagents.
MATERIALS AND METHODS
Seventy-two HDM sensitized allergic patients were enrolled and classified into four groups: 1) control (n=27), 2) SCIT with Hollister-Stier® (n=19), 3) Tyrosine S® (n=16), and 4) Novo-Helisen® (n=10). Levels of specific IgE (sIgE), sIgG4, and IgE blocking factor to Dermatophagoides farinae (D. farinae) were measured using ImmunoCAP (sIgE, sIgG4) and enzyme-linked immunosorbent assay (ELISA) (IgE-blocking factors). Levels were measured before and 13.9±6.6 months after the SCIT. The allergen specificity and the induction levels of sIgE and sIgG4 were confirmed by immunoblot analysis.
RESULTS
After SCIT, sIgG4 levels to D. farinae increased significantly; however, the increases differed significantly among the SCIT groups (p<0.001). Specific IgG4 levels to D. farinae were highest in Hollister-Stier® (3.7±4.1 mg/L), followed by Novo-Helisen® (2.2±2.3 mg/L) and Tyrosine S® (0.7±0.5 mg/L). In addition, patients who were administered using Hollister-Stier® showed the most significant decrease in IgE/IgG4 ratio (p<0.001) and increase in blocking factor (p=0.009). Finally, according to IgE immunoblot results, the Hollister-Stier® group showed the most significant attenuation of IgE binding patterns among others.
CONCLUSION
Currently available SCIT reagents induce different levels of specific IgG4, IgE/IgG4 ratio, and IgE-blocking factor.

Keyword

Blocking factor; house dust mite; IgG4; immunotherapy; specific IgE

MeSH Terms

Adult
Allergens/administration & dosage/*immunology
Animals
Antibody Specificity/immunology
Antigens, Dermatophagoides
*Antigens, Neoplasm
Dermatitis, Atopic/blood/*immunology/*therapy
Desensitization, Immunologic/*methods
Enzyme-Linked Immunosorbent Assay
Female
Humans
Immunoglobulin E/blood/*immunology
Immunoglobulin G/blood/*immunology
Injections, Subcutaneous
Male
Mites/*immunology
Pyroglyphidae/immunology
Treatment Outcome
Young Adult
Allergens
Antigens, Dermatophagoides
Antigens, Neoplasm
Immunoglobulin G
Immunoglobulin E

Figure

• 

  Fig. 1 Comparison of immunologic parameters before and after immunotherapy. Dermatophagoides farinae-specific IgE titers (A), specific IgG4 titers (B), specific IgE/IgG4 ratio (C), before and after immunotherapy. Data represent the mean±standard error of the mean. *p value<0.05, †p value<0.005. IT, immunotherapy; IgE, immunoglobulin E; IgG4, immunoglobulin G4.

• 

  Fig. 2 BF index. Measurement of BF index (A), and its results (B). Data represent the mean±standard error of the mean. *p value<0.05. IT, immunotherapy; IgE, immunoglobulin E; OD, optical density; BF, blocking factor.

• 

  Fig. 3 Dermatophagoides farinae-specific IgE immunoblot using sera from five patients in each group: Hollister-Stier® (A), Tyrosine S® (B), Novo-Helisen® (C), (a) before (b) after immunotherapy. Numbers 1–5 designate individual patients in each group. Specific IgE levels of Der p 2 of the five patients in each group are also shown (D). IgE, immunoglobulin E.

• 

  Fig. 4 Dermatophagoides farinae-specific IgG4 immunoblot using sera from five patients in each group: Hollister-Stier® (A), Tyrosine S® (B), Novo-Helisen® (C), (a) before (b) after immunotherapy. Numbers 1–5 designate individual patients in each group. Specific IgG4 levels (D) and blocking factor index (E) of the five patients in each group. IgG4, immunoglobulin G4.

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