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Allergens in Hymenoptera venom. XXI. Cross-reactivity and multiple reactivity between fire ant venom and bee and wasp venoms.

The relationships between fire ant venom and bee and wasp venoms were explored by studying sera from five groups of subjects. Group 1 included adults not allergic to any venoms and who were not exposed to fire ants. Group 2 included adults with fire ant exposure who were not allergic to venoms. Group 3 included patients with recent systemic reactions to fire ant venom. Group 4 included patients allergic to bee and vespid venoms with no fire ant exposure. Last, group 5 included patients allergic to bee and vespid venoms with fire ant exposure. None of the serum samples from group 1 was RAST reactive to fire ant venom, but 24% of those from group 2 were fire ant positive, as were 100% of those from group 3, 51% of those from group 4, and 87% of those from group 5. The RAST-positive patients in groups 2 and 5 were also skin test positive. RAST inhibition studies demonstrated cross-reactivity in some cases and multiple reactivity in others. The serum samples were further investigated via nondenaturing electrophoretic immunoblot studies and RAST with highly purified allergens. Serum samples from group 4 reacted to a single band on immunoblots and with only one of the four purified allergens from fire ant venom (Solenopsis invicta I, or Sol i I). Serum samples from groups 2, 3, and 5 showed various patterns of allergen reactivity. All serum samples from patients allergic to fire ant venom who also reacted to bee and/or vespid venoms by RAST contained IgE antibodies binding to Sol i I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Allergens in Hymenoptera venoms. IV. Comparison of venom and venom sac extracts.

Honeybee venom sac extract is compared with pure venom. All five known allergens of venom are present in venom sac extract. Enzyme analyses indicate that the sac extracts contain 11% to 16% venom. At least 10 additional components, several of which are proteins, are present in venom sac extract. Radioallergosorbent test (RAST) studies of yellow jacket venom and venom sac extract yielded a correlation of r = 0.94, with only some weakly reactive sera positive to only one preparation. A few sera were substantially more reactive with venom sac extract. Venom sac extracts appear to be suitable for in vitro diagnostic use, but the extraneous proteins and peptides may make them less suitable than pure venoms for use in immunotherapy.

Acid Phosphatase

Analysis of differing patterns of cross-reactivity of honeybee and yellow jacket venom-specific IgE: use of purified venom fractions.

Prior studies of sera from insect sting-allergic patients have analyzed the relationship of coexisting honeybee venom- and yellow jacket venom-specific IgE. Radioallergosorbent (RAST)-inhibition tests with these venoms revealed four different patterns of activity. In this present study, purified fractions prepared from these venoms were used to analyze these varying patterns. The hyaluronidases of yellow jacket venom and honeybee venom showed extensive cross-reaction. The phospholipases from these venoms showed minimal cross-reactivity; antigen 5 was restricted to yellow jacket venom. There was a high molecular weight component in yellow jacket venom with immunologic properties similar to honeybee venom acid phosphatase. Sera from individual patients showed quantitative and qualitative differences in the reactions to the major components of both venoms. The differences in the RAST-inhibition patterns in patients with elevated levels of both honeybee venom- and yellow jacket venom-specific IgE are accounted for by these differences as well as by differences in the cross-reactivity between the individual components.

Animals

Late onset reactions following venom immunotherapy and venom skin tests.

This report describes patients who had late onset reactions following venom immunotherapy and venom skin tests. Six adult patients had symptoms of fatigue, malaise, fever, headache, and joint ache, starting four to six hours after venom immunotherapy and lasting up to four days. Two of the patients had prolonged reactions at or adjacent to the skin test sites. All of these patients had a history of venom anaphylaxis; four had severe cardiovascular symptoms. All received yellow jacket venom immunotherapy and four honeybee venom immunotherapy. In four patients, the reactions occurred following small venom doses, 0.1 to 2 micrograms. Two patients reacted after maintenance doses of 50 micrograms. There was no relationship to the serum IgE or IgG antibody titers. All but one patient had serum venom-specific IgE but the titers covered a wide range. Serum venom-specific IgG was present in four patients. There was no response in lymphocyte culture to bee venom stimulation in two patients. Two of these patients stopped venom immunotherapy; one had reached the maintenance dose. In three patients, prophylactic parenteral steroids have ameliorated the reactions. After a temporary dose reduction, the sixth patient is now asymptomatic. A seventh patient developed asthma, 12 hours following a maintenance dose of 50 micrograms of yellow jacket venom. Concomitant steroid administration has effectively prevented the reaction. Another patient, a 6-year-old boy, developed fever, edema of the face and lips, erythema of the leg, and a large, tender right inguinal node eight hours following venom skin tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans

Classification of myonecrosis induced by snake venoms: venoms from the prairie rattlesnake (Crotalus viridis viridis), western diamondback rattlesnake (Crotalus atrox) and the Indian cobra (Naja naja naja).

The pathogenesis of myonecrosis induced by three different snake venoms was studied by light microscopic examination of skeletal muscle tissue taken at time periods ranging from 0.25 hr to 4 weeks after an intramuscular injection of the venom into mice. It was possible to identify different types of myonecrosis based on the abnormal morphologic states of the damaged cells. The types of myonecrosis observed correlated with the types of components present in the venom injected. Venoms containing direct acting toxins such as myotoxin a or phospholipase A2 induced specific types of myonecrosis. Also, venoms containing hemorrhagic toxins produced a type of myonecrosis similar to that induced by pure hemorrhagic toxins. The pathogenesis of each type of myonecrosis could be divided into the same four phases based on the pathologic states of the affected cells and the time after injection. During the 'early phase' (0.25-3 hr) affected muscle cells were in several different pathologic states reflecting the types of components present in the venom injected. During the 'intermediate phase' (6-24 hr) the pathologic state of the damaged cells had changed and depending on the venom new states might be present. By the 'late phase' (48-96 hr) all damaged cells have reached a common pathologic state of necrosis. The 'final phase' (1-4 weeks) is characterized by regeneration (partial or complete) of muscle cells. Although the number of different types of myonecrosis depended on the type of venom injected, i.e. Naja naja naja venom produced only two different types whereas Crotalus atrox venom produced at least four different types, cells of each tpe of myonecrosis progressed through the same four phases. In studies of the myotoxicity of snake venoms it is important to examine tissues taken during the early and intermediate phases to obtain accurate and useful information on the types of myonecrosis caused by the venom.

Animals

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.

Bee Venoms

Antigenic relationship between the venom of the night adder Causus maculatus and venoms of other viperids.

Monovalent antivenoms were raised in mice against the venoms of Causus maculatus, Vipera ammodytes, Echis carinatus, Cerastes cerastes, Bitis arietans, Agkistrodon rhodostoma and Bothrops atrox. These antivenoms as well as four commercially available antivenoms were tested against the venoms of 15 viperid species by means of immunoelectrophoresis and/or ELISA. Cross-reactive protein bands were determined by immunoblot. ELISA cross-reactions of C. maculatus antivenom were low with all heterologous venoms. When investigating the other viperine antivenoms in ELISA stronger cross-reactions were observed with several heterologous venoms. In immunoblot, two heterologous antivenoms cross-reacted with one or two protein bands of C. maculatus venom whereas there were at least four heterologous antivenoms cross-reacting with each of the other venoms. The findings indicate that there is little antigenic affinity between C. maculatus venom and the other venoms investigated. Broad in vitro cross-reactions between viperine antivenoms and Causus venom which were reported in literature seem to be attributable to the use of antivenoms of commercial grade. Specificity of commercially produced, mono- or polyvalent antivenoms may not be strictly limited to those venoms, against which potency is claimed on the label of the product.

Animals

The Hymenoptera venom study. II: Skin test results and safety of venom skin testing.

Data are summarized in this Hymenoptera venom study (HVS) article on the safety of skin testing with venom extracts. Of the 3236 subjects studied, 89% had experienced an historical sting systemic reaction (SSR). Seventy-four percent of all subjects and 76% of subjects who had experienced an historical SSR had a positive skin test to at least one venom. More subjects tested positive to yellow jacket venom (51.8%) than to any other venom. There were no significant differences of the wheal and erythema sizes associated with different venoms or different historical sting reactions. Forty-five percent of subjects with positive venom skin tests (VST) were positive to wasp, and 89% of these subjects were also positive to at least one of the following venoms: yellow jacket, yellow hornet, or white-faced hornet. Sixty-four of the 3236 subjects studied (2%) had a systemic reaction (SR) during VST; 13 of the SRs (0.4%) were severe. Thirteen of 64 adverse reactions (20%) were possibly vasovagal, and six other subjects (9%) demonstrated no symptoms of immediate-type hypersensitivity. Thus, 45 (1.4%) of the 3236 subjects tested had an SR that was considered to be a reaction of hypersensitivity, of which eight reactions (0.25%) were severe. Allergic SRs are associated with VST but are unusual and are rarely severe.

Animals

Snake venoms in science and clinical medicine. 2. Applied immunology in snake venom research.

Enzyme-linked immunosorbent assay (ELISA) is a very important tool for studying both the epidemiology and clinical effects of snake bite in man. For epidemiology ELISA depends on the development and persistence of specific humoral venom antibody in previous snake bite victims. In the Nigerian savanna 63% of previous bite victims possessed specific venom antibodies against Echis carinatus venom; in Ecuador, where there is a 5% annual mortality due to snake bite in a population of Waorani Indians, venom antibodies against a wide range of different venoms were identified in previous bite victims using ELISA. In certain areas it is often not possible, using the symptoms of envenoming, to determine which species of snake has bitten the patient. Field studies using ELISA in Nigeria and Thailand have been successful in establishing the species responsible for envenoming. Current studies are in progress on the development of a rapid immunoassay which should be capable of detecting the biting species within 5-10 min of sampling from the admission patient. This will be useful for the clinician as it will enable the rapid detection of the species responsible for envenoming and, therefore, the use of the correct antivenom. Experimental work on the development of new methods of antivenom production includes immunization of experimental animals with venom/liposome preparations, the preparation of venom antigens using monoclonal antibodies on affinity columns, and recombinant deoxyribonucleic acid technology. Liposomal immunization requires only a single injection of venom to obtain a rapid, high level and protective immune response. Venom liposomes may also be given orally resulting in a serum immunoglobulin G immune response in experimental animals. Use of such a system may eventually result in immunization of man in areas of high snake bite incidence and mortality.

Animals

Factors influencing the hemolysis of human erythrocytes by cardiotoxins from Naja naja kaouthia and Naja naja atra venoms and a phospholipase A2 with cardiotoxin-like activities from Bungarus fasciatus venom.

The effects of red blood cell age and incubation conditions (temperature, divalent cation type and concentration, pH and glucose) on hemolysis induced by cardiotoxin fractions from Naja naja atra and Naja naja kaouthia venoms, a phospholipase A2 with cardiotoxin-like activities from Bungarus fasciatus venom and bee venom phospholipase A2 were examined. Hemolysis by the snake venom toxins was dependent on red blood cell age (aged more susceptible than fresh) and the temperature of incubation (37 degrees C greater than 20 degrees C). Divalent cations at 0.5-2.0 mM enhanced (Ca2+) or slightly decreased (Sr2+, Ba2+) hemolysis due to N. n. kaouthia and N. n. atra toxins, and greatly decreased (Ca2+, Sr2+, Ba2+) hemolysis by these toxins at higher concentrations (5-40 mM). For the B. fasciatus phospholipase A2, Ba2+ and Sr2+ could not fully support hemolysis in any concentration while both low (less than 0.5 mM) and high (greater than 40 mM) Ca2+ enhanced hemolysis. Bee venom phospholipase A2 only induced hemolysis (greater than 10% at greater than 40 mM) at high concentrations of Ca2+. Increasing the pH from 7.5 to 8.5 greatly increased the levels of hemolysis by the snake venom toxins and enzyme. Glucose (5.3 mM) increased hemolysis by the snake venom components at low concentrations of divalent cations (2 mM) and slightly decreased hemolysis at high concentrations (40 mM). Treatment with p-bromophenacyl bromide abolished phospholipase A2 activity of bee venom and B. fasciatus phospholipases, but did not affect hemolytic potency of N. n. kaouthia or B. fasciatus toxins. A similar mechanism, which is independent of phospholipase A2 activity, may be involved in hemolysis by the N. n. kaouthia and N. n. atra cardiotoxins. The B. fasciatus cardiotoxin-like phospholipase A2 appears to have two mechanisms of hemolysis; the first is similar to that of the two typical cardiotoxins and the second appears dependent on phospholipase A2 activity and is only evident at high Ca2+ concentrations.

Bungarotoxins

Venom immunotherapy: 10 years of experience with administration of single venoms and 50 micrograms maintenance doses.

For the past 10 years, we have administered venom immunotherapy with single venoms, whenever it is possible, and maintenance doses of 50 micrograms. The choice of venoms was based on clinical history, skin test reactions, and a knowledge of venom cross-reactivity. There have been 258 re-stings in 108 patients with only three systemic reactions (2.7% per patient; 1.2% per sting). Two of these re-stings reactions were very mild, hives and facial edema, in patients who had had initial severe anaphylaxis. Five other patients had transient ill-defined symptoms, not considered allergic after re-stings. The patients covered a wide age range. Twenty-seven patients, nine under age 16 years, had initial dermal reactions only, and 44 patients had severe anaphylaxis. Most patients had multiple positive skin tests. Seventy-five patients received single venoms (yellow jacket, 58; honeybee, 15; hornet, 2), and 30 patients received two venoms. Re-stings occurred from 1 month to 8 years, (mean, 2 years) after starting treatment. Results indicate that this approach with 50 micrograms top doses and single venom immunotherapy may be sufficient in most patients with an associated decrease in the cost as well as possible increased morbidity associated with the use of multiple venom antigens.

Adolescent

Venomous Lepidoptera: defensive toxin systems, venom composition, and clinical significance.

Venomous Lepidoptera constitute an underrecognized yet medically significant group of toxin-producing arthropods that employ contact-mediated defensive envenomation through specialized integumentary structures such as setae, spines, and scoli. Unlike actively stinging arthropods, these insects deliver venom passively upon contact, eliciting a diverse spectrum of clinical manifestations collectively termed lepidopterism. Clinical outcomes range from localized pain and dermatitis to severe systemic effects, including hemorrhagic syndromes, complement activation, and chronic inflammatory disorders. Recent advances in proteomic and transcriptomic technologies have transformed our understanding of lepidopteran venoms, revealing unexpectedly complex toxin repertoires comprising serine proteases, phospholipases, pore-forming proteins, disulfide-rich peptides, neuroactive RF-amide peptides, and immune-modulating components. These findings have provided new insights into the molecular basis of toxicity, host-pathogen interactions, and the evolutionary diversification of venom systems within Lepidoptera. This review synthesizes current knowledge on the morphology of venom-delivery structures, venom composition, mechanisms of action, and associated clinical manifestations, while highlighting medically important taxa, particularly species of the genus Lonomia. The successful development of antivenom against Lonomia envenomation underscores the translational relevance of lepidopteran toxin research and its potential for therapeutic innovation. By integrating molecular, clinical, and evolutionary perspectives, this review repositions venomous Lepidoptera as a legitimate and important component of arthropod toxinology. Furthermore, it identifies critical methodological limitations and key knowledge gaps, providing a framework for future investigations aimed at advancing our understanding of toxin biology, immunopathology, and the development of novel biomedical applications.

Animals

Inhibition of human platelet aggregation and secretion by ant venom and a compound isolated from venom.

Venom from the tropical ant, Pseudomyrmex triplarinus, has activity against rheumatoid arthritis. Since platelets are involved in inflammatory responses, they were employed to study the effects of venom on prostaglandin-dependent human platelet aggregation and secretion. The assay is very sensitive and uses microliter volumes, which makes it useful as a screen during isolation and characterization of venom components. Whole venom inhibited arachidonic acid- and U46619-induced platelet aggregation with IC50s of 45 and 39 micrograms/ml, respectively. This suggested that venom prevented the action of prostaglandins. Pure venom was fractionated by gel filtration and at least three materials with antiplatelet activity were detected. The smallest component (factor F) was most active and was purified by additional molecular filtration and characterized by UV absorbance, thin-layer chromatography, nuclear magnetic resonance spectra, and activity to platelets. Factor F was identified as adenosine, which is known to stimulate platelet adenylate cyclase and has not been previously reported to be a component of insect venom.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

Immunotherapy with honeybee venom and yellow jacket venom is different regarding efficacy and safety.

Venom immunotherapy (VIT) for Hymenoptera allergy is accepted as safe and effective. However, widely varying success rates and frequencies of side effects are reported. Differences between various Hymenoptera species could account for these diverging results. We therefore analyzed 205 patients with a history of systemic allergic reactions to either honeybee (148 patients) or yellow jacket stings (57 patients) during VIT. All patients had a positive skin test to the respective venom before VIT, were monitored for side effects of VIT, and submitted to a sting challenge while they were receiving VIT. Patients with honeybee-venom allergy had a higher sensitivity in both skin tests (p less than 0.05) and RAST (p less than 0.001) than patients with yellow jacket-venom allergy. They developed systemic side effects to VIT injections significantly more often (41% versus 25%; p less than 0.01) and also reacted more frequently to the sting challenge (23% versus 9%; p less than 0.01) than patients with yellow jacket-venom allergy. We conclude that results obtained from studies on the allergy to one Hymenoptera venom cannot be extrapolated to allergies to other Hymenoptera venoms.

Acute Disease

Kinins in ant venoms--a comparison with venoms of related Hymenoptera.

1. Venom preparations have been made of six ant, one pompilid wasp, two mutillid wasp, and four social wasp species. 2. The venoms were analysed pharmacologically in order to detect kinin-like activity. 3. Due to the small amounts of venoms available only a cascade of smooth muscle preparation could be used. 4. Kinin activities have been found in five ant venoms and in four social wasp venoms. 5. No kinin activity has been found in the venoms of the pompilid and mutillid wasps. 6. All ant venoms also contain unidentified agonists for vertebrate smooth muscle preparations.

Animals

Clinical correlation of the venom-specific IgG antibody level during maintenance venom immunotherapy.

Allergen immunotherapy is associated with a significant increase of specific IgG antibodies that have been suggested as a mechanism of action and as a marker of efficacy for immunotherapy. The value of venom-specific IgG antibody determinations as a measure of clinical protection against sting anaphylaxis has been difficult to prove in individual patients. We performed 211 insect sting challenges in 109 patients over a 4-year period to determine the significance of venom IgG levels 3 micrograms/ml or lower. Systemic symptoms occurred in only 1.6% of those with venom IgG more than 3 micrograms/ml, but in 16% of those with less than 3 micrograms/ml IgG, and notably in 26% of patients with low venom IgG who had received less than 4 years of treatment. The venom IgG level had no predictive value in patients who had received more than 4 years of therapy. Honeybee sting data were inconclusive because of the small number of subjects. We conclude that low venom-specific IgG levels are associated with an elevated risk of treatment failure during the first 4 years of immunotherapy with yellow jacket or mixed vespid venoms.

Adult

The use of enzyme-linked immunosorbent assay for the quantitation of Calloselasma rhodostoma (Malayan pit viper) venom and venom antibodies.

The specificity and sensitivity of an indirect and two (an 'ordinary' and a 'rapid') double sandwich enzyme-linked immunosorbent assay (ELISA) procedures for the quantitation of Calloselasma rhodostoma (Malayan pit viper) venom were examined. The three assays were equally sensitive and the accuracy of the assays was not substantially affected by individual variation in the venom composition. The specificity of the assays was examined against 26 venoms from snakes of the families Viperidae and Elapidae. While the double sandwich ELISA procedures were sufficiently specific to be used in the clinical immunodiagnosis of C. rhodostoma bite in Malaysia, the indirect ELISA procedure exhibited extensive cross-reactivity with other Malaysian pit viper venoms. Attempts were made to improve the specificity of the indirect ELISA procedure for the quantitation of C. rhodostoma venom. A 'low ELISA cross-reactivity' venom fraction (termed VF52) was isolated from C. rhodostoma venom by repeated Sephadex G-100 gel filtration chromatography. The indirect ELISA procedure using antibodies to VF52 as immunoreagent showed an improvement in specificity. The use of the indirect ELISA procedure for the detection of C. rhodostoma antibodies was also examined and the results show that the assay was sufficiently specific to be used for retrospective diagnosis of C. rhodostoma bite in Malaysia, in particular when VF52 was used as the coating antigen.

Antibody Specificity