DOSE-RESPONSE OF IGE AND IGG ANTIBODIES DURING RAGWEED IMMUNOTHERAPY

The detailed dose-response relationship for ragweed (RW) antibody responses in 51 patients who received maximal-dose immunotherapy with crude RW extract was studied. Serum RW-IgG and RW-IgE levels were determined by solid-phase radioimmunoassay at frequent intervals during initiation and maintenance of immunotherapy. Pretreatment RW-IgE ranged from 0.94 to 974 ng/ml (median 105); 45/51 patients had insignificant levels (< 250 ng/ml) of RW-IgG. The maximal doses given ranged from 0.19 to 93.5 .mu.g of RW antigen E/injection. All patients produced a significant IgG response (median peak 3462 ng/ml, range 689 to 24.395), and 46/51 had significant increases in IgE antibody (median peak 231 ng/ml, range 12 to 1528). A threshold dose was defined for each patient''s IgG and IgE response as that dose level which initiated a persistent increment in immunoglobulin to .gtoreq. 25% of pretreatment levels. The median threshold dose for IgE was 0.13 .mu.g of antigen E, which was achieved in a median time of 42 days. The threshold dose for IgG was significantly higher (median 0.56 .mu.g of antigen E; P = 0.001) and occurred significantly later (median 79 days; P = 0.003). Despite variability > 3 orders of magnitude, the thresholds for IgE and IgG responses were significantly correlated for individual patients (r = 0.487, P = 0.002). The maximum RW-IgE response occurred in a median of 107 days, after which IgE antibodies declined in 46 of 49 patients. The maximal IgG response occurred significantly later (median 245 days; P < 0.001) and then plateaued or declined modestly. The doses required to achieve maximal IgE and IgG responses were significantly correlated (r = 0.638; P < 0.001). The maximum IgG response was positively correlated with the maximal dose of RW antigen E received (r = 0.592; P < 0.001). In 28 of the 51 patients, the incremental rise in total serum IgE was more than twice that observed for RW-IgE at the time of the maximum response, suggesting a nonspecific effect of RW immunotherapy on total serum IgE levels. This discrepancy could not be accounted for by environmental stimulation from other known allergens, as assessed by skin testing, or by pretreatment levels of RW-IgE or total IgE. Evidently, the human IgE antibody response during high-dose RW immunotherapy is more sensitive to both stimulation and suppression by continuous allergen administration than is the IgG response. This finding may have implication both for understanding of the in vivo regulation of immune response during allergen immunotherapy and for future attempts to modify specific IgE antibody responses in man.