Molecular reactivity profiling upon immunotherapy with a 300 IR sublingual house dust mite tablet reveals marked humoral changes towards major allergens

Abstract

Background Molecular antibody reactivity profiles have not yet been studied in depth in patients treated by sublingual house dust mite (HDM) tablet immunotherapy. Humoral immune responses to a large panel of HDM mite allergens were studied using allergen microarray technology in a subset of clinically defined high and low responder patients from a double‐blind placebo‐controlled allergen‐specific immunotherapy (AIT) trial using sublingual 300 IR HDM tablets. Methods Serum levels of IgE, IgG and IgG4 to 13 Dermatophagoides pteronyssinus molecules were measured at baseline and after 1‐year AIT, using allergen microarrays in 100 subjects exhibiting high or low clinical benefit. Results Der p 1, Der p 2 and Der p 23 were the most frequently recognized allergens in the study population. Patients with HDM‐related asthma had significantly higher allergen‐specific IgE levels to Der p 1 and Der p 23. No significant difference in the distribution of allergen sensitization pattern was observed between high and low responders. An increase in serum allergen‐specific IgG and IgG4 occurred upon AIT, in particular to allergens Der p 1, Der p 2 and Der p 23 (p < 0.0001). Conclusions We confirm for our study population that Der p 1‐ and Der p 23‐specific IgE levels are associated with asthma. IgE reactivity profiles were not predicitive of sublingual AIT outcomes, with 300 IR tablets as efficacious in pauci‐ and multi‐sensitized subjects. Our study is the first to demonstrate the induction of IgG and IgG4 specific for the HDM allergens Der p 1, Der p 2 and Der p 23 by sublingual AIT.

Monitoring of molecular profiling of allergen-antibody responses in HDM-immunotherapy patients

“…Similar conclusions were drawn by other authors who investigated the problem of neosensitization in the course of 12 months-long AIT with HDM extract. 13–15 – 18 In agreement with our findings, those authors did not report significant changes in the profiles of molecular sensitizations against major and minor molecules during subcutaneous 15 , 16 and sublinqual 13 , 14 immunotherapy. Running counter to both the abovementioned and our own observations is the paper of Gellrich et al, regarding the development of neosensitizations in the cohort of 51 patients subject to SCIT with different groups of allergens for over 12 months (Fagales (N = 18), Poaceae (N = 19) and HDM (N = 14)), which suggests that such occurrences may take place.…”

“…Overall, the baseline reactivity of sIgE as well as the molecular sensitization profile regarding the major and minor HDM allergens examined in our study were coincident with the profiles analyzed in other studies. 14 Similar to other authors, we determined dominant sensitizations to three molecules Der p 2, Der p 1 and Der p 23, whereby sensitizations to the last one were in the lower range of the frequency of such occurrences, which may be accounted for by geographical specificity of synchronization to Der p 23 and/or by low numbers of patients with allergic rhinitis and concomitant asthma in whom sensitization to Der p 23 is more frequent. 11 …”

“… 15 , 22 However, the thesis is challenged by Potapova et al, who reported a significant rise in IgG and IgG4 against Der p 1, 2, 23 as well as Der p 4, 15, 18 and 37 during HDM SLIT. 14 Finally, it might be possible that neosensitizations in the course of AIT develop over a period of time longer than 12 months, which was raised by Gellich et al 19 This possibility was considered, and the authors of the present study continued observation of the study group. However, this investigation was conducted with unmatched stored sera in which the controls were not necessarily selected by the same criteria.…”

“…Potapova et al noted the same effect in a group of patients who were administered HDM SLIT. 14 In her study, concentrations of sIgE against most molecules decreased after 12 months of AIT. The author postulates that this phenomenon may result from an increase in IgG4 reactivity and the resultant competitive binding of IgE via IgG.…”

“… 12 Nevertheless, there is no proven clinical evidence that might confirm such claims. 13 , 14 The issue of de novo sensitizations to other HDM molecules, which might undermine the optimal efficacy of AIT, is an ongoing subject of discussion. 13–16 …”