Diagnosis and immunotherapy of mould allergy. VIII. Qualitative and quantitative estimation of IgE in Cladosporium immunotherapy.
The interrelation of in vitro IgE-mediated parameters, i.e. serum-specific IgE (RAST), basophil cell-bound specific IgE, and histamine release from basophil leucocytes was investigated in a 1-year placebo-controlled, double-blind Cladosporium immunotherapy study involving 22 adult asthmatics. The intense and early burst (within 6 weeks of immunotherapy) of serum-specific IgE did not result in a corresponding increased binding of specific IgE molecules to basophils. Cell-bound IgE increased in the Cladosporium season in both groups at the same time as serum levels of specific IgE declined in the Cladosporium group. In the placebo group histamine release from circulating basophils paralleled changes in basophil-bound IgE. In Cladosporium-treated patients, histamine release cell sensitivity after a lag phase (during immunotherapy dose-increase) declined two log steps, i.e. the cells became less responding in spite of a significant increase in cell-bound IgE. To further evaluate the sensitizing capacity of circulating specific IgE, passive sensitization studies were performed using basophils from a single donor. Although sera taken at the maximal IgE-response showed an enhanced capacity of passive sensitization, the ratio between RAST and passive sensitization capacity increased significantly in Cladosporium-treated patients, implying a less than expected sensitization capacity of immunotherapy-induced specific IgE. The lack of active binding of IgE to basophils might be explained by a reduced Fc-affinity of immunotherapy-induced IgE in contrast to the Cladosporium-seasonally induced IgE. Regarding the decrease in histamine release in Cladosporium-treated patients in spite of an increased amount of cell-bound specific IgE, immunotherapy may initiate a decrease in mediator releasibility which is not caused by a reduction in the number of Fc-receptors but rather some yet unknown subcellular mechanisms regulating the histamine release. The described changes in IgE-mediated parameters do not seem to be caused by interference with either specific IgG1 or IgG4. Changes in histamine release in the Cladosporium season were the only IgE-mediated parameter significantly related to the graded clinical efficacy of immunotherapy.
Malling
H J
HJ
Laboratory of Clinical Allergology, Medical Department TTA, State University Hospital, Copenhagen, Denmark.
Stahl Skov
P
P
D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000628:therapy*; D001491:Basophils / Q000378:metabolism; D002963:Cladosporium / Q000276:immunology*; D006636:Histamine Release; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000032:analysis* / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D003904:Mitosporic Fungi / Q000276:immunology*; D011897:Random Allocation
D007074:Immunoglobulin G; D007073:Immunoglobulin E