Evaluation of Recombinant and Native Timothy Pollen (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4)- Specific IgG4 Antibodies Induced by Subcutaneous Immunotherapy with Timothy Pollen Extract in Allergic Patients

Abstract

Background: Allergen immunotherapy is a widely accepted treatment for IgE-mediated allergies. The evaluation of immunotherapy-induced IgG4 antibodies based on allergen extract is questionable because the amount of allergen-extract-specific IgG4 to individual disease-eliciting allergens cannot be determined using crude allergen extracts. In this study, we examined the specific IgE and IgG4 serum binding profiles to individual Phleum pratense allergens in grass-pollen-sensitive patients who had received grass-pollen-specific immunotherapy (SIT). Methods: The study included 33 patients from North-West Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. A modified ‘cluster’ regimen of injections of a standardized aluminium-adsorbed P.pratense extract, with once-weekly visits and 10 injections for 5 weeks followed by 3 weeks of maintenance injections was instituted. Patients’ sera were analyzed for specific IgE and IgG4 reactivity to individual P. pratense allergens (recombinant Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 7, Phl p 11, Phl p12 and native Phl p 4) and natural P. pratense extract using the Pharmacia CAP system. Results: IgE reactivities to new allergen components were not detected by CAP in treated patients after 15 weeks and a cumulative dose of approximately 65 µg of the major allergen Phl p 5. Patients lacking specific IgE reactivity towards individual allergens at the start of SIT did not produce significant levels of specific serum IgG4 to serum IgE-negative allergens. On the other hand, an increase in specific IgG4 only to allergens to which patients were previously sensitized was observed. Significant increases in specific IgG4 levels to rPhl p 1 (p < 0.05), 2 (p < (0.01), 5 (p < 0.0001), 6 (p < 0.0001), 7 (p < 0.05), 11 (p < 0.05) and nPhl p 4 (p < 0.01) were observed after P. pratense extract immunotherapy. No significant rPhl p 12-specific IgG4 antibody increase was documented after treatment. Conclusion: These findings suggest that Phl p 12 was underrepresented in the extract used, as indicated by the low specific IgG4 response induced by this grass-pollen-specific vaccine. Thus, the simple detection of specific serum IgG4 antibodies a few weeks after the start of SIT could represent a valuable tool to estimate the presence of relevant allergens in a given immunotherapeutic allergen extract.

Specific allergen immunotherapy for the treatment of allergic asthma: a review of current evidence

“…In asthmatic and nonasthmatic children with house dust mites (HDM) allergy, the IgE and IgG reactivity profiles to HDM allergens, as well as IgE levels to certain allergen components, differed considerably between both groups; asthmatic children showed an expanded IgE repertoire to allergen components and increased specific IgE levels [41]. This pattern was also observed in a similar study in an Italian population [35]. One publication established an association between sensitization to minor allergens of olivetree pollen and poor tolerance to specific immunotherapy, with patients sensitized to Ole e 7 or 9 showing a 2-fold greater risk of asthmatic symptoms than patients sensitized only to Ole e 1 [42].…”

“…The detection of specific serum IgG4 antibodies a few weeks after the start of AIT was a valuable tool to estimate the presence of relevant allergens in the immunotherapeutic allergen extract [35]. It has been shown that IgE response against grass pollen molecules can start years before symptoms onset as a weak sensitization phenomenon.…”

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008*

“…Recombinant allergens have been used for the in vitro diagnosis of grass (1206,1207,1213,1246,1247), birch and Fagaleae (1248)(1249)(1250)(1251)(1252)(1253), Oleaceae (1199,1254), pollens or mites (1255)(1256)(1257). A single recombinant allergen or a combination of a few major recombinant allergens can substitute the crude extract for in vitro diagnostic purposes (1258,1259).…”

Developments in allergen‐specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen‐specific immunoglobulin E and T cell reactivity

“…Often treatment-induced increases of allergen-specific IgE are moderate and might be overcome by the induction of high levels of allergen-specific IgG [21,[48][49][50][51][52][53]. Treatmentinduced increases of allergen-specific IgE up to the fourfold baseline levels have been observed in a recent SLIT study whereas allergen-specific IgG remained very low [44,54].…”