Of the 13 allergen groups identified in grass pollen, four – Phl p 4, 7, 11, and 12 – are not grass-specific, while the other groups are grass-specific. Considering the classification of allergens as major or minor depending on their recognition by IgE antibodies from more or less than 50% of sensitised patients, respectively, Group 1 and Group 5 contain the major grass pollen allergens. Group 1 allergens are acidic glycoproteins, with a m.w. of 31–35 kDA, and have high homology (about 90% of the amino acid sequence) [
16], while Group 5 allergens are proteins showing ribonuclease activity, occurring in two non-glycosilated isoforms, with a m.w. of 27–33 kDa, which have a lesser homology due to a 25-30% divergence in amino acid sequence [
4]. Instead, Phl p 7, a calcium-binding protein, and Phl p 12, a profilin, are ubiquitous molecules showing cross-reactivity in a number of allergen sources that are not naturally found as specific grass pollen allergens [
4]. Due to the complex allergen repertoire of grass pollen, the pattern of sIgE response of sensitised individual is largely variable, especially concerning the recognition of the different epitopes expressed in the various allergens. The sensitisation is obviously influenced by the kind of exposure and particularly by the distribution of the different grasses in the geographical area where the patients live. For example,
Phleum pratense clearly prevails in Northern Europe, while is less present in central and southern Italy, as demonstrated by phenologic studies [
17]. The contact of the immunologic system with the allergens introduced by means of specific immunotherapy is a different kind of stimulation, that is potentially able to induce a sIgE response to allergen components previously not recognized by natural exposure. This was true in the study by Ball et al, who found a
de novo induction of sIgE against new allergens in one of 8 patients treated with SCIT with a grass pollen extract. This finding lead the authors to suggest the
de novo sensitisation as a factor able to explain the unpredictability of specific immunotherapy performed with allergen extracts [
11]. Similar observations were reported by Moverare et al. in a larger group of 34 patients allergic to birch pollen treated with SCIT, 29% of whom developed new sensitizations to rBet v 2 and/or rBet v 4, though the sIgE levels were low and the clinical relevance was not known [
18]. Indeed, other investigations on grass-allergic patients, namely 33 subjects from North-West Italy [
12] and 19 subjects from Germany [
13] treated with SCIT did not find any new sensitisation. The only available study on sIgE profiles to grass pollen allergens during SLIT was performed on 40 adults treated with a
Phleum pratense extract in tablets. Most patients had low titers of sIgE to Phl p 1 and Phl p 5 before SLIT and showed a dose-dependent increase during the treatment, while sIgE titers to Phl p 7 and Phl p 12 were very low both before and after SLIT; no new sensitisation was detected [
14].
We addressed the present study to evaluate the changes in sIgE levels to Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 7, and Phl p 12 in children treated with SLIT using a 5-grass extract which was demonstrated to be immunologically effective [
19,
20]. Significant increases were detected for Phl p 1, Phl p 2, Phl p 5, and Phl p 6, but not for Phl p 7 and Phl p 12, which maintained the pre-treatment low levels. We confirmed the lack of new sensitisations, and this is important because the immunologic stimulation given by a 5-grass extract is wider than that by an extract with a single grass. Also sIgG4 were measured, with detection of significant increase for Phl p 2 and Phl p 5 but not for Phl p 12. Concerning the latter, the mild increase (from 0.14 to 0.21 mg/ml) excludes that the low level of sIgE was influenced by the blocking activity of IgG4. For the other allergens, a substantially parallel pattern of IgE and IgG4 response was found. This result is in agreement with previous observations [
14]. Our results cannot be generalized, considering the extreme heterogeneity of the immune-response to grass pollen, as recently reported by Tripodi et al. [
21]. In particular, it is not known whether the production of sIgE to the different allergen components is influenced by only genetic predisposition or also by the kind of allergen exposure. In addition, it remains to be investigated if a prolonged period of observation during SLIT could detect changes in sIgE specificities not occurring in early phases of treatment.