Monitoring allergen immunotherapy of pollen-allergic patients: the ratio of allergen-specific IgG4 to IgG1 correlates with clinical outcome

Background Although allergen immunotherapy has been established as a treatm ent of type I allergy back in 1911, until now the underlying mechanisms hav e not been fully understood, nor are there any parameters which would allow one to monitor an ongoing treatment or to assess therapeutic success in th e meantime. Objective We wanted to define allergen-specific parameters that change due to treatment in correlation with the clinical outcome. Methods We conducted a controlled study with grass pollen-allergic children and compared allergen-specific antibody titres before and 1 year after the onset of immunotherapy in contrast with untreated allergic and healthy chi ldren. Two recombinant forms of the major allergen group V of Phleum praten se (Phl p 5) served as model allergens. Results No change in IgE levels and no significant reduction of skin prick test (SPT) reactivity were seen. On the other hand, a significant reduction of symptom scores in the treated group and a significant rise in allergen- specific IgG1, IgG2 and IgG4 due to the treatment could be observed, but in neither case could we establish a correlation between the increasing amoun ts of the single antibody classes and the reduction of symptom scores. But most interestingly, when comparing the ratio of IgG4 to IgG1 with the symto m scores, we found significant correlations. Nevertheless, treated allergic patients still differ considerably from healthy controls as nonatopics hav e hardly any measurable allergen-specific IgG antibodies and no IgE antibod ies at all. Conclusion The ratio of IgG4 to IgG1 can serve as a valuable parameter that allows us to assess the success of immunotherapy already 1 year after the onset. The increase of specific IgG1 in relation to IgG4 during treatment r eflects a possible influence of this subclass on the induction of tolerance towards allergens.