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Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract.
J Allergy Clin Immunol. 2016 Feb; 137(2):562-70.JA

Abstract

BACKGROUND

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.

Authors+Show Affiliations

Departments of Respiratory Medicine and Allergy, Aarhus University Hospital, Aarhus, Denmark.Global Research, ALK-Abelló, Hørsholm, Denmark.Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.Departments of Respiratory Medicine and Allergy, Aarhus University Hospital, Aarhus, Denmark. Electronic address: hjh@clin.au.dk.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

26141262

Citation

Schmid, Johannes Martin, et al. "Pretreatment IgE Sensitization Patterns Determine the Molecular Profile of the IgG4 Response During Updosing of Subcutaneous Immunotherapy With Timothy Grass Pollen Extract." The Journal of Allergy and Clinical Immunology, vol. 137, no. 2, 2016, pp. 562-70.
Schmid JM, Würtzen PA, Dahl R, et al. Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract. J Allergy Clin Immunol. 2016;137(2):562-70.
Schmid, J. M., Würtzen, P. A., Dahl, R., & Hoffmann, H. J. (2016). Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract. The Journal of Allergy and Clinical Immunology, 137(2), 562-70. https://doi.org/10.1016/j.jaci.2015.05.023
Schmid JM, et al. Pretreatment IgE Sensitization Patterns Determine the Molecular Profile of the IgG4 Response During Updosing of Subcutaneous Immunotherapy With Timothy Grass Pollen Extract. J Allergy Clin Immunol. 2016;137(2):562-70. PubMed PMID: 26141262.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract. AU - Schmid,Johannes Martin, AU - Würtzen,Peter Adler, AU - Dahl,Ronald, AU - Hoffmann,Hans Jürgen, Y1 - 2015/06/30/ PY - 2015/01/30/received PY - 2015/05/11/revised PY - 2015/05/12/accepted PY - 2015/7/5/entrez PY - 2015/7/5/pubmed PY - 2016/7/1/medline KW - Grass pollen allergy KW - allergen component–specific IgE KW - allergen component–specific IgG(4) KW - allergen immunotherapy biomarker KW - component-resolved diagnosis KW - molecular allergy KW - subcutaneous immunotherapy SP - 562 EP - 70 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 137 IS - 2 N2 - BACKGROUND: 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/26141262/Pretreatment_IgE_sensitization_patterns_determine_the_molecular_profile_of_the_IgG4_response_during_updosing_of_subcutaneous_immunotherapy_with_timothy_grass_pollen_extract_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(15)00729-0 DB - PRIME DP - Unbound Medicine ER -