Pretreatment IgE sensitization patterns determine the molecular profile of the IgG₄ response during updosing of subcutaneous immunotherapy with timothy grass pollen extract

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• 作者：Johannes Martin Schmid ; MD^a ; Peter Adler Wü ; rtzen ; PhD^b ; Ronald Dahl ; DrSciMed^c ; ^&lowast ; ; Hans Jü ; rgen Hoffmann ; PhD^a ; ^{hjh@clin.au.dk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Grass pollen allergy ; subcutaneous immunotherapy ; component-resolved diagnosis ; allergen component&ndash ; specific IgE ; allergen component&ndash ; specific IgG4 ; molecular allergy ; allergen immunotherapy biomarker
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：137
• 期：2
• 页码：562-570
• 全文大小：959 K

文摘

Allergen immunotherapy is an effective treatment of allergic rhinoconjunctivitis. Clinical efficacy is associated with improvement of basophil sensitivity and an increase in allergen-specific immunoglobulin concentration.

Objective

We sought to determine whether changes in allergen component–specific serum IgE and IgG₄ levels during the updosing phase of subcutaneous immunotherapy (SCIT) are biomarkers of the immunologic changes that can lead to treatment efficacy.

Methods

Twenty-four subjects with grass pollen–induced allergic rhinoconjunctivitis were randomized 3:1 to receive SCIT (Alutard SQ) or to an open control group. IgE and IgG₄ concentrations were determined for the major allergens Phl p 1 or Phl p 5 by using ImmunoCAP and for 8 grass pollen molecules by using Immuno Solid-phase Allergy Chip (ISAC) before treatment and after updosing.

Results

Levels of specific IgE against the dominant major allergens Phl p 1 and Phl p 5 increased from a mean of 23.0 to 48.8 kU/L (P = .01, n = 18) during the updosing phase in ImmunoCAP measurements but decreased from a median of 4.6 ISAC specific units (ISU) to 2.14 ISU (P < .0001, n = 102) when measured by using ISAC against 8 grass allergen components. The updosing phase induced a specific IgG₄ level increase from a median of 0 ISU before treatment to 0.83 ISU after 12 weeks (P < .0001, n = 102) but only for allergen molecules to which pretreatment-specific IgE antibodies were detected (Spearman σ = 0.72, P < .0001, n = 102).

Conclusion

Pretreatment allergen component–specific IgE appears to determine the induction of IgG₄ in the updosing phase. Induced IgG₄ seems to suppress IgE levels on ISAC, resulting in a marked decrease in ISAC-measured specific IgE levels after updosing of SCIT. Thus this decrease in ISAC IgE levels can be used to monitor the blocking effect of allergen-specific immunotherapy–induced non-IgE antibodies.