The role of immunotherapy in ragweed hay fever has been investigated by a combination of clinical and laboratory technics. In the clinical study a course of immunization with the principal antigen of ragweed (antigen E) was compared to placebo injections in matched groups of patients. Double blind evaluation of the patient's symptoms was performed in a semiquantitative fashion by patient diary and physician examination. The laboratory study involved an in vitro model of human allergic reactions: the antigenically induced release of histamine from the isolated leukocytes of sensitive donors. This system allows an independent evaluation of cellular reactivity and the level of blocking antibodies, the latter measured by their ability to inhibit the in vitro allergic response. The sensitivity of an untreated donor's cells to ragweed antigen E correlated significantly (P < 0.01) with the degree of clinical illness suffered during the season of ragweed pollination. Immunotherapy did not change the dose-response relationships of the sensitive cells, but the cell sensitivity symptom correlation was altered so that the symptoms in the treated patients were less than predicted by their cell sensitivity. Blocking antibody was increased by immunization to levels several thousandfold greater than control. The antibody response correlated significantly with the quantity of antigen E administered (17 to 800 μg.). Of eighteen pairs of treated and placebo patients, matched by cell sensitivity measurements, the treated partner had an appreciably lower symptom score in 10 pairs, there was little difference in 7 pairs and the untreated partner had a lower score in one pair (p < 0.01). The patients with the higher levels of antibody did better, on the average, than those with the lower. The relationship, however, was neither precise nor constant. This may be due to the lack of precision inherent in evaluating symptoms, but it is also possible that antibodies closer to the target organ, e.g., in the nasal secretions, are more important than serum antibodies.
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