Background: At present, there are no validated biomarkers reflecting or predicting the clinical efficacy of allergen-specific immunotherapy (AIT) . We aimed to investigate the correlations between clinical and immunological responses of patients undergoing house dust mite (HDM) AIT. Methods: Sixty-nine children diagnosed with HDM allergic rhinitis and/or asthma received standardized Dermatophagoidespteronyssinus (Dp) subcutaneous AIT for 12 months. Twenty HDM-allergic children served as an open control group. Clinical symptom and medication scores were recorded and Dp-specific IgE, IgG4 and IgE-blocking factor were measured before AIT and after 4 and 12 months of AIT. Results: Symptom scores decreased after 4 months and continued to decrease during 12 months of AIT. No differences in medication scores were observed between AIT and the control group during the study period. Levels of Dp IgG4 increased after 4 months and correlated to symptom scores at 12 months (r = -0.296, p = 0.013) of AIT. The Dp IgE-blocking factor increased after 4 months of AIT, and correlated with symptom scores at 4 months (r = -0.307, p = 0.010) and 12 months (r = -0.288, p = 0.016) of AIT. A strong correlation between Dp IgE-blocking factor and Dp IgG4 during AIT (4 months: r = 0.680; 12 months: r = 0.636, both p < 0.0001) was observed. Patients with IgE-blocking factor ≥0.2 after 4 months of AIT showed lower symptom scores at 12 months of AIT (p = 0.0093). Conclusions: Subcutaneous HDM AIT results in a decrease of allergic symptoms among HDM-allergic children. IgE-blocking activity increased after 4 months of AIT and correlated with clinical symptoms. A high IgE-blocking factor at an early stage of AIT is associated with fewer symptoms at a later stage of AIT.

1.
Larenas-Linnemann DES, Pietropaolo-Cienfuegos DR, Calderón MA: Evidence of effect of subcutaneous immunotherapy in children: complete and updated review from 2006 onward. Ann Allergy Asthma Immunol 2011;107:407-416.
2.
Erekosima N, Suarez-Cuervo C, Ramanathan M, Kim JM, Chelladurai Y, Segal JB, Lin SY: Effectiveness of subcutaneous immunotherapy for allergic rhinoconjunctivitis and asthma: a systematic review. Laryngoscope 2014;124:616-627.
3.
Jacobsen L, Niggemann B, Dreborg S, Ferdousi HA, Halken S, Høst A, Koivikko A, Norberg LA, Valovirta E, Wahn U, Möller C; THE PAT investigator group: Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy 2007;62:943-948.
4.
Aalberse RC, van der Gaag R, van Leeuwen J: Serological aspects of IgG4 antibodies. I. prolonged immunization results in a IgG4-restricted response. J Immunol 1983;130:722-726.
5.
Lai X, Li J, Xiao X, Liu E, Zhang C, Wang H, Gjesing B, Zhong N, Spangfort MD: Specific IgG4 production during house dust mite immunotherapy among age, gender and allergic disease populations. Int Arch Allergy Immunol 2013;160:37-46.
6.
Wachholz PA, Durham SR: Mechanisms of immunotherapy: IgG revisited. Curr Opin Allergy Clin Immunol 2004;4:313-318.
7.
van Neerven RJ, Wikborg T, Lund G, Jacobsen B, Brinch-Nielsen A, Arnved J, Ipsen H: Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation. J Immunol 1999;163:2944-2952.
8.
Wachholz PA, Kristensen Soni N, Till SJ, Durham SR: Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J Allergy Clin Immunol 2003;112:915-922.
9.
van Neerven RJ, Arvidsson M, Ipsen H, Sparholt SH, Rak S, Würtzen PA: A double-blind, placebo controlled birch allergy vaccination study: inhibition of CD23-mediated serum immunoglobulin E-facilitated allergen presentation. Clin Exp Allergy 2004;34:420-428.
10.
Würtzen PA, Lund G, Lund K, Arvidsson M, Rak S, Ipsen H: A double-blind placebo-controlled birch allergy vaccination study II: correlation between inhibition of IgE binding, histamine release and facilitated allergen presentation. Clin Exp Allergy 2008;38:1290-1301.
11.
van der Zee JS, van Swieten P, Aalberse RC: Inhibition of complement activation by IgG4 antibodies. Clin Exp Immunol 1986;64:415-422.
12.
Aalberse RC, Stapel SO, Schuurman J, Rispers T: Immunoglobulin G4: an odd antibody. Clin Exp Allergy 2009;39:469-477.
13.
Flicker S, Valenta R: Renaissance of the blocking antibody concept in type I allergy. Int Arch Allergy Immunol 2003;132:13-24.
14.
Shamji MH, Ljørring C, Francis JN, Calderon MA, Larché M, Kimber I, Frew AJ, Ipsen H, Lund K, Würtzen PA, Durham SR: Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. Allergy 2012;67:217-226.
15.
James LK, Shamji MH, Walker SM, Wilson DR, Wachholz PA, Francis JN, Jacobson MR, Kimber I, Till SJ, Durham SR: Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies. J Allergy Clin Immunol 2011;127:509-516.e5.
16.
Li J, Sun B, Huang Y, Lin X, Zhao D, Tan G, Wu J, Zhao H, Cao L, Zhong N; China Alliance of Research on Respiratory Allergic Disease: A multicenter study assessing the prevalence of sensitizations in patients with asthma and/or rhinitis in China. Allergy 2009;64:1083-1092.
17.
Francis JN, James LK, Paraskevopoulos G, Wong C, Calderon MA, Durham SR, Till SJ: Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J Allergy Clin Immunol 2008;121:1120-1125.e2.
18.
Petersen AB, Gudmann P, Gronager PM, Morkeberg R, Bogestrand S, Linneberg A and Johansen N: Performance evaluation of a specific IgE assay developed for the ADVIA Centaur® immunoassay system. Clin Biochem 2004;37:882-892.
19.
Glymour MM, Weuve J, Berkman LF, Kawachi I, Robins JM: When is baseline adjustment useful in analyses of change? An example with education and cognitive change. Am J Epidemiol 2005;162:267-278.
20.
Garofolo KM, Yeatts SD, Ramakrishnan V, Jauch EC, Johnston KC, Durkalski VL: The effect of covariate adjustment for baseline severity in acute stroke clinical trials with responder analysis outcomes. Trials 2013;14:98.
21.
Wang H, Lin X, Hao C, Zhang C, Sun B, Zheng J, Chen P, Sheng J, Wu A, Zhong N: A double-blind, placebo-controlled study of house dust mite immunotherapy in Chinese asthmatic patients. Allergy 2006;61:191-197.
22.
Blumberga G, Groes L, Dahl R: SQ-standardized house dust mite immunotherapy as an immunomodulatory treatment in patients with asthma. Allergy 2011;66:178-185.
23.
Pevec B, Radulovic Pevec M, Stipic Markovic A, Batista I, Rijavec M, Silar M, Kosnik M, Korosec P: House dust mite-specific immunotherapy alters the basal expression of T regulatory and FcεRI pathway genes. Int Arch Allergy Immunol 2012;159:287-296.
24.
Yukselen A, Kendirli SG, Yilmaz M, Altintas DU, Karakoc GB: Effect of one-year subcutaneous and sublingual immunotherapy on clinical and laboratory parameters in children with rhinitis and asthma: a randomized, placebo-controlled, double-blind, double-dummy study. Int Arch Allergy Immunol 2012;157:288-298.
25.
Shamji MH, Wilcock LK, Wachholz PA, Dearman RJ, Kimber I, Wurtzen PA, Larché M, Durham SR, Francis JN: The IgE-facilitated allergen binding (FAB) assay: validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses. J Immunol Methods 2006;317:71-79.
26.
Holm J, Willumsen N, Wurtzen PA, Christensen LH, Lund K: Facilitated antigen presentation and its inhibition by blocking IgG antibodies depends on IgE repertoire complexity. J Allergy Clin Immunol 2011;127:1029-1037.
27.
James LK, Bowen H, Calvert RA, Dodev TS, Shamji MH, Beavil AJ, McDonnell JM, Durham SR, Gould HJ: Allergen specificity of IgG4-expressing B cells in patients with grass pollen allergy undergoing immunotherapy. J Allergy Clin Immunol 2012;130:663-670.
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