De novo sensitization during subcutaneous allergen specific immunotherapy - an analysis of 51 cases of SCIT and 33 symptomatically treated controls

Abstract

Since the beneficial implementation of allergen specific subcutaneous immunotherapy (SCIT), there are only a few studies on the risk of SCIT-induced neosensitizations. In 51 patients, we retrospectively analyzed sige and sigG patterns by a multiplex eLiSA as well as demographic and clinical features before and after SCIT. 33 allergic patients, who only received symptomatic treatment, served as controls. In 12 of 51 SCIT-treated patients (24%), we found new sIgE against allergen components of the allergen source treated by Scit; eight of them were adults. Among controls, no adult patient showed neosensitization to components of the primarily affected allergen source. Only two children of the control group were affected by neosensitization, which was limited to major allergen components and rarely accompanied by sIgG. In the SCIT-treated group, neosensitization affected major and minor allergen components, and was accompanied by a strong induction of sIgG against major components. A clear clinical predictor of neosensitization during Scit was not found. comparing symptom scores, patients seem to profit more from SCIT, if neosensitization remained absent. Patients undergoing SCIT might carry an enhanced risk of neosensitization towards formerly unrecognized allergen components. According to anamnestic data, these neosensitizations might be of clinical relevance -supporting attempts towards personalized recombinant vaccines.Since the implementation of allergen specific immunotherapy (SIT) in clinical practice, many studies have been conducted to analyze the immunological changes during SIT 1 . Many publications focus on the antibody responses induced by SIT in general and the antibody shift from IgE to IgG subclasses in particular 2 .However, there are only a few studies on the potential induction of new sensitizations by SIT. The exposure to allergens, especially if combined with adjuvants, might lead to new sensitization to formerly unrecognized allergen epitopes 3,4 . With regard to venom SIT, the neosensitization to minor allergens has been described 5 . Concerning other important allergen sources, conflicting results are found: Regarding house dust mite (HDM) and grass pollen, the percentage of de novo sensitizations toward minor allergens differ from 0% 6-10 to 8-12% 11-13 .One major influencing variable might be the observation period: Studies with short-term observation after one course of SIT or less tend to exclude neosensitization 7-10 , possibly by missing middle-or long-term immunological changes occurring only after longer period of repetitive exposure to the allergen. However, all studies reporting de novo sensitization induced by SIT had a longer observation period 12,13 except for the publication by Baron-Bodo et al. in 2013 11 detecting neosensitization in 10% of patients treated by grass pollen sublingual immunotherapy (SLIT) for four months only. With regard to de novo sensitization induced by birch pollen SIT, all three published studies report on cases of neosensitization [14][15][16] .Another ...

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

“…No major change was observed in prevalence of IgE reactivity after 1 year treatment. In agreement with previous studies reporting limited neosensitizations in patients undergoing AIT, 33,34,46,47 we observed in the present study, a few patients with IgE levels rising above the 0.3 ISU positivity threshold. In most cases, the induction of IgE was counterbalanced by an increase of IgG/IgG 4 .…”

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

“… 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.…”

“…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. 19 …”

Sensitisation to Imbrasia belina (mopane worm) and other local allergens in rural Gwanda district of Zimbabwe

“…A categorical variable was generated from duration of mopane worm harvesting whereby a period of 2 years was considered a reasonable period in which a neo-sensitisation can occur. This was derived from studies reporting sensitisation to neo-allergens following immunotherapy [ 47 , 48 ]. Participants reporting a harvesting duration of less than 2 years, including no harvesting at all, were included in the comparison group for this variable.…”