Simplified AIT for allergy to several tree pollens—Arguments from the immune outcome analyses following treatment with SQ tree SLIT‐tablet

BACKGROUND: The SQ tree SLIT‐tablet (containing birch extract) proved clinically significant effects during the pollen season for birch as well as alder/hazel. Immune outcomes of this treatment for allergens from multiple birch homologous trees need further investigation. We hypothesize that birch pollen extract AIT modulates a highly cross‐reactive immune response and that this may be the basis for the observed clinical cross‐protection. METHODS: Blood samples were collected from 397 birch allergic patients during SQ tree SLIT‐tablet or placebo treatment (1:1) for up to 40 weeks. Serum IgE and IgG(4) specific to birch, and birch homologous tree pollens from alder, hazel, hornbeam, beech and chestnut were measured by ImmunoCAP. IgE‐Blocking Factor (IgE‐BF) for alder, birch and hazel during treatment was measured by Advia Centaur and blocking effects for birch and all these birch homologous tree pollens were further investigated by basophil activation (BAT). Antibody readouts were investigated in patient subsets. T‐cell responses (proliferation) to allergen extracts and peptide pools (group 1 allergens) were investigated in T‐cell lines from 29 untreated birch pollen‐allergic individuals. RESULTS: Significant Pearson correlations between serum IgE towards birch, alder, hazel, hornbeam and beech were observed (r‐values > .86). T‐cell reactivity was observed throughout the birch homologous group. Almost identical kinetics for changes in IgE towards birch, alder and hazel were observed during treatment and similar species‐specific changes were seen for serum‐IgG(4). IgG(4) reactivity towards birch and alder, hazel, hornbeam and beech correlated significantly at end‐of‐treatment (r‐values > .72). Treatment resulted in similar IgE‐BF kinetics for alder, birch, and hazel and blocking of BAT for multiple trees in most actively treated patients investigated. CONCLUSIONS: Systematic analyses of T‐cell and antibody cross‐reactivities before and during birch pollen extract AIT provide the immunological basis for the observed clinical effect of SQ tree SLIT‐tablet treatment of tree pollen allergy induced by multiple trees in the birch homologous group.