Bee Venom Immunotherapy Research Articles

SUBCLASS TYPING OF SPECIFIC IGG ANTIBODIES IN ALLERGEN IMMUNOTHERAPY

Allergen immunotherapy results in the production of allergen specific antibodies. We investigated whether antibody response in one or more of the four IgG subclasses may be correlated to the clinical improvement. 10 patients suffering from systemic reactions to bee stings were hyposensitized over 3 years. All patients tolerated a bee stingchallenge one, two, and 3 years after the start of treatment, and after bee venom immunotherapy was discontinued. Almost all of the IgG antibodies were restricted to IgG1 and IgG4 subclasses. Although both rose during treatment, IgG4 were maintained at high levels when immunotherapy was discontinued. In conclusion, in serum from normal individuals IgG1 is the predominant main protective antibody. IgG4 subclass specific antibodies appear as a result of a repeat antigenic stimulation as in allergen immunotherapy. Our findings of persisting clinical protection and IgG4 predominant immune response support the protective role of IgG4 in allergic individuals undergoing a venom hyposensitization treatment.

Discontinuation of bee venom immunotherapy in children and adolescents

Sixty-six patients with a history of systemic allergy reactions to bee stings, positive skin prick test to less than or equal to 100 micrograms/ml bee venom, and positive radioallergosorbent test (RAST) results were given venom immunotherapy. IgE and IgG antibodies to bee venom were measured by RAST and enzyme-linked immunosorbent test (ELISA), respectively. IgE and IgG anti-bee venom levels rose initially, but subsequently fell during immunotherapy. In 31 patients in whom specific IgE fell to low (less than 6% counts bound) or unmeasurable levels, immunotherapy was discontinued, and sting challenge was carried out 1 to 3 years later. All patients tolerated sting challenge well. The specific IgE and IgG antibody levels did not change significantly after treatment was stopped. Our data suggest that hyposensitization treatment can be stopped when specific IgE serum concentrations have fallen to low or unmeasurable levels and specific IgG antibody values are maintained, and that in a considerable number of patients venom immunotherapy has a lasting therapeutic and immunologic effect.

Bee-sting mortality in Australia.

Death as a result of a bee sting is uncommon in Australia. During the 22 years from 1960 to 1981, 25 individuals have been recorded by the Australian Bureau of Statistics as having died shortly after a bee sting. This gives a mortality incidence of 0.086/1 000 000 population per year, but may be an underestimate, as we report two additional fatalities that did not appear in the records of the Bureau of Statistics. South Australia has the highest mortality rate from bee stings of all the Australian States, with a recorded fatality rate of 0.26/1 000 000 population per year. As in other surveys, fatalities occur predominantly in men over 40 years of age, which suggests that there may be other contributory risk factors, for example, coronary atherosclerosis. No deaths were reported in individuals aged from six to 19 years, the age group in which bee-sting anaphylaxis is particularly common. It thus appears that the prevention of death per se is not a strong rationale for routine bee-venom immunotherapy in schoolchildren and young adults.

Antibodies to purified bee venom proteins and peptides: II. A detailed study of changes in IgE and IgG antibodies to individual bee venom antigens

Antibodies to individual bee venom antigens were studied in detail in nine bee sting-allergic patients who received venom immunotherapy without side effects, in two patients who failed to reach maintenance, and in two whose sensitivity returned. The study was confined to patients who had IgE antibodies to at least one of four purified bee venom antigens at the start of treatment. IgE and IgG antibodies to phospholipase A 2 (PLA 2 ), hyaluronidase (HYAL), and acid phosphatase (ACID P) and IgE antibodies to melittin (MEL) were measured, and changes in the antibody levels were followed during bee venom immunotherapy. Two contrasting patterns of antibody response were seen in the nine successfully treated patients. In five patients there was a rise in serum IgG antibodies to the same antigens as the IgE antibodies. In two patients' serum IgE antibody to HYAL or ACID P fell without a marked IgG antibody response to these antigens, although high levels of IgG antibody to PLA 2 were present in both. Although the first pattern is consistent with a “blocking” role for IgG antibody, clearly the second is not. Not all patients can be conveniently divided into these two categories, and two patients did not show any significant change in either IgG or IgE antibody but were nevertheless able to tolerate the maintenance dose of 100 μg of venom. Two patients who failed to reach the maintenance dose of 100 μg because of their allergic reactions to the injections of venom were distinguished by (1) very high serum IgE antibody and (2) a low ratio of IgG/IgE antibody. Passive immunization with IgG antibody from a hyperimmune beekeeper was, however, protective in these patients, although it did not raise their overall serum IgG antibody level very much. We are unable to explain either the failure of conventional therapy or the beneficial effect of passive immunization in these two patients. Two bee sting-allergic beekeepers lost their sensitivity to stings, but later, when their sera contained IgE antibody to another bee venom antigen, they reacted to stings and inhalation of beehive dander. These data suggest that either falling IgE antibody or IgG-“blocking” antibody could be responsible for providing clinical protection to bee venom-allergic subjects. Renewed clinical sensitivity was observed when the IgE response was modulated, with patients making IgE antibody first to one antigen and then to another.

Enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G antibodies against insect venoms

IgG “blocking” antibodies were measured in patients receiving insect venom immunotherapy. The enzyme-linked immunosorbent assay (ELISA) described herein was found to be sensitive and reproducible. Results with ELISA correlated well with values obtained with a radioimmunoassay and with inhibition of the release of histamine from sensitive basophils. Also, specific antibody titers against phospholipase A and whole bee venom were correlated. Serial determinations of venom-specific IgG antibodies were made in 17 patients receiving Polistes wasp or bee venom immunotherapy. The majority of patients showed a rise in IgG antibodies, which peaked after administration of approximately 500 μg of venom. Only one out of 13 of these venom-treated patients had allergic symptoms after an insect sting while on maintenance therapy.

IgE antibodies to bee venom, phospholipase A, melittin and wasp venom.

Specific IgE antibodies against bee venom, phospholipase A, melittin and wasp venom have been examined in fifty patients with an unusually severe reaction after bee or wasp sting. Two thirds of the bee venom-sensitive patients also have detectable IgE antibodies to wasp venom. More than 50% of the wasp venom-sensitive patients are also allergic to bee venom. Phospholipase A and melittin IgE antibodies were found, respectively, in two thirds and one third of the bee venom-sensitive cases. Specific IgE antibody determinations by the Radioallergosorbent test play an essential role in the diagnostic work. After a reaction to hymenoptera stings both bee and wasp venom tests are necessary due to the high incidence of a false or incomplete identification of the stinging insect. Melittin, known for its potent pharmacological activity and possibly responsible for most of the side effects in bee venom immunotherapy, can probably not be excluded from therapeutic venom preparations since IgE antibodies to the melittin preparation were detected in one third of the cases.

Clinical and immunological studies of venom immunotherapy

SummaryClinical and immunological studies were conducted in fifty insect‐sensitive patients receiving bee and yellow jacket venom immunotherapy. All patients had had anaphylactic reactions and had elevated serum levels of venom‐specific IgE (RAST) prior to therapy. Venom injections were given weekly starting at a dose of about 0.001 μg and aiming for a maximum of 50 μg or greater. Maintenance injections were administered monthly.In the majority of patients, venom‐specific IgG was produced by immunizing doses above 1 μg. Highest titres were related to higher doses. Almost all patients receiving doses of 50 μg of venom had an IgG antibody response.Sequential measurements of venom‐specific IgE were done in thirty‐seven patients. Twenty‐two had a declining titre, ten had a persistently elevated titre and five patients had a rise in antibody titre. There was no relationship between IgE and IgG antibody titres except for four patients who had a marked rise of both antibodies following venom therapy. Ten of the fifty patients received subsequent stings with no reactions. At the time of the subsequent uneventful sting, all but one had detectable serum IgG antibodies.These studies suggest: (1) venom immunotherapy appears effective for immunization of insect‐sensitive individuals; and (2) considerable variability in individual immunological response to therapy and thus the probable need to individualize the degree and extent of venom therapy.