RESUMO
Insect venom phospholipases have been identified in nearly all clinically relevant social Hymenoptera, including bees, wasps and ants. Among other biological roles, during the envenoming process these enzymes cause the disruption of cellular membranes and induce hypersensitive reactions, including life threatening anaphylaxis. While phospholipase A2 (PLA2) is a predominant component of bee venoms, phospholipase A1 (PLA1) is highly abundant in wasps and ants. The pronounced prevalence of IgE-mediated reactivity to these allergens in sensitized patients emphasizes their important role as major elicitors of Hymenoptera venom allergy (HVA). PLA1 and -A2 represent valuable marker allergens for differentiation of genuine sensitizations to bee and/or wasp venoms from cross-reactivity. Moreover, in massive attacks, insect venom phospholipases often cause several pathologies that can lead to fatalities. This review summarizes the available data related to structure, model of enzymatic activity and pathophysiological roles during envenoming process of insect venom phospholipases A1 and -A2.
Assuntos
Venenos de Artrópodes/enzimologia , Himenópteros/enzimologia , Mordeduras e Picadas de Insetos/imunologia , Fosfolipases A1/imunologia , Fosfolipases A2/imunologia , Sequência de Aminoácidos , Animais , Venenos de Artrópodes/imunologia , Humanos , Mordeduras e Picadas de Insetos/enzimologia , Fosfolipases A1/química , Fosfolipases A1/metabolismo , Fosfolipases A2/química , Fosfolipases A2/metabolismoRESUMO
Along with food and drug allergic reactions, a Hymenoptera insect Sting (Apoidea, Vespidae, Formicidae) is one of the most common causes of anaphylaxis worldwide. Diagnoses of Hymenoptera venom allergy (HVA) and specific immunotherapy (SIT) have been based on the use of crude venom extracts. However, the incidence of cross-reactivity and low levels of sensibility during diagnosis, as well as the occurrence of nonspecific sensitization and undesired side effects during SIT, encourage the search for novel allergenic materials. Recombinant allergens are an interesting approach to improve allergy diagnosis and SIT because they circumvent major problems associated with the use of crude venom. Production of recombinant allergens depends on the profound molecular characterization of the natural counterpart by combining some "omics" approaches with high-throughput screening techniques and the selection of an appropriate system for heterologous expression. To date, several clinically relevant allergens and novel venom toxins have been identified, cloned and characterized, enabling a better understanding of the whole allergenic and envenoming processes. Here, we review recent findings on identification, molecular characterization and recombinant expression of Hymenoptera venom allergens and on the evaluation of these heterologous proteins as valuable tools for tackling remaining pitfalls on HVA diagnosis and immunotherapy.
Assuntos
Alérgenos/imunologia , Venenos de Artrópodes/imunologia , Himenópteros/imunologia , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Alérgenos/genética , Alérgenos/uso terapêutico , Animais , Venenos de Artrópodes/genética , Venenos de Artrópodes/uso terapêutico , Clonagem Molecular , Dessensibilização Imunológica , Humanos , Himenópteros/metabolismo , Proteoma , Proteínas Recombinantes , TranscriptomaRESUMO
CONTEXT AND OBJECTIVE: The only effective treatment for patients who have severe reactions after Hymenoptera stings is venom immunotherapy. The aim of this study was to review the literature to assess the effects of venom immunotherapy among patients presenting severe reactions after Hymenoptera stings. DESIGN AND SETTING: Randomized controlled trials in the worldwide literature were reviewed. The manuscript was produced in the Discipline of Allergy and Clinical Immunology, Universidade de São Paulo (USP). METHODS: Randomized controlled trials involving venom immunotherapy versus placebo or only patient follow-up were evaluated. The risk of systemic reactions after specific immunotherapy was evaluated by calculating odds ratios (OR) and their 95% confidence intervals. RESULTS: 2,273 abstracts were identified by the keywords search. Only four studies were included in this review. The chi-square test for heterogeneity showed that two studies were homogeneous and could be included in a meta-analysis. By combining the two studies, the odds ratio became significant: 0.29 (0.10-0.87). However, analysis on the severity of the reactions after immunotherapy showed that the benefits may not be so significant because the reactions were mostly similar to or milder than the original reaction. CONCLUSIONS: Specific immunotherapy should be recommended for adults and children with moderate to severe reactions, but there is no need to prescribe it for children with skin reactions alone, especially if the exposure is very sporadic. On the other hand, the risk-benefit relation should always be assessed in each case.
Assuntos
Venenos de Artrópodes/uso terapêutico , Himenópteros/imunologia , Hipersensibilidade/terapia , Imunoterapia/métodos , Animais , Venenos de Artrópodes/imunologia , Venenos de Abelha/imunologia , Venenos de Abelha/uso terapêutico , Distribuição de Qui-Quadrado , Humanos , Hipersensibilidade/imunologia , Mordeduras e Picadas de Insetos/imunologia , Mordeduras e Picadas de Insetos/terapia , Razão de Chances , Resultado do Tratamento , Venenos de Vespas/imunologia , Venenos de Vespas/uso terapêuticoRESUMO
CONTEXT AND OBJECTIVE: The only effective treatment for patients who have severe reactions after Hymenoptera stings is venom immunotherapy. The aim of this study was to review the literature to assess the effects of venom immunotherapy among patients presenting severe reactions after Hymenoptera stings. DESIGN AND SETTING: Randomized controlled trials in the worldwide literature were reviewed. The manuscript was produced in the Discipline of Allergy and Clinical Immunology, Universidade de São Paulo (USP). METHODS: Randomized controlled trials involving venom immunotherapy versus placebo or only patient follow-up were evaluated. The risk of systemic reactions after specific immunotherapy was evaluated by calculating odds ratios (OR) and their 95 percent confidence intervals. RESULTS: 2,273 abstracts were identified by the keywords search. Only four studies were included in this review. The chi-square test for heterogeneity showed that two studies were homogeneous and could be included in a meta-analysis. By combining the two studies, the odds ratio became significant: 0.29 (0.10-0.87). However, analysis on the severity of the reactions after immunotherapy showed that the benefits may not be so significant because the reactions were mostly similar to or milder than the original reaction. CONCLUSIONS: Specific immunotherapy should be recommended for adults and children with moderate to severe reactions, but there is no need to prescribe it for children with skin reactions alone, especially if the exposure is very sporadic. On the other hand, the risk-benefit relation should always be assessed in each case.
CONTEXTO E OBJETIVO: O único tratamento eficaz para pacientes que têm reações graves após ferroada de Hymenoptera é a imunoterapia com veneno. O objetivo deste estudo foi rever a literatura para avaliar os efeitos da imunoterapia com veneno em pacientes com reações graves após ferroada de Hymenoptera. TIPO DE ESTUDO E LOCAL: Foram revisados na literatura mundial ensaios clínicos controlados e aleatórios. O manuscrito foi realizado na Disciplina de Alergia e Imunologia Clínica, Universidade de São Paulo (USP). MÉTODOS: Ensaios clínicos controlados e aleatórios envolvendo imunoterapia com veneno de Hymenoptera versus placebo ou apenas acompanhamento dos pacientes foram avaliados. Realizada imunoterapia específica, o risco de reações sistêmicas foi avaliado através de cálculo do "odds ratio" e intervalo de confiança de 95 por cento. RESULTADOS: 2.273 resumos foram identificados na busca pelas palavras chave. Apenas quatro estudos foram incluídos nesta revisão. O teste qui-quadrado de heterogeneidade mostrou que dois estudos foram homogêneos e puderam ser incluídos na metanálise. Ao combinar os dois estudos, o "odds ratio" passou a ser significativo: 0.29 (0.10-0.87). Entretanto, ao analisar a gravidade das reações ocorridas após a imunoterapia, observou-se que os benefícios podem não ser tão relevantes, pois as reações foram, na grande maioria, ou mais leves ou semelhantes à reação original. CONCLUSÕES: A imunoterapia específica deve ser recomendada para adultos e crianças com reações moderadas a graves, porém não há necessidade de prescrevê-la para as crianças apenas com reações cutâneas, especialmente se a exposição é muito esporádica. No outro lado, a relação risco-benefício deve ser sempre avaliada em cada caso.
Assuntos
Humanos , Animais , Venenos de Artrópodes/uso terapêutico , Himenópteros/imunologia , Hipersensibilidade/terapia , Imunoterapia/métodos , Venenos de Artrópodes/imunologia , Venenos de Abelha/imunologia , Venenos de Abelha/uso terapêutico , Distribuição de Qui-Quadrado , Hipersensibilidade/imunologia , Mordeduras e Picadas de Insetos/imunologia , Mordeduras e Picadas de Insetos/terapia , Razão de Chances , Resultado do Tratamento , Venenos de Vespas/imunologia , Venenos de Vespas/uso terapêuticoRESUMO
Centipedes have a venom gland connected to a pair of forceps, which are used to arrest preys. Human victims bitten by centipedes usually manifest burning pain, paresthesia and edema, which may develop into superficial necrosis. The aim of this work was to characterize and compare toxic activities found in venoms of three species of Brazilian centipedes-Otostigmus pradoi, Cryptops iheringi and Scolopendra viridicornis. By SDS-PAGE (4-20%), important differences were noticed among venoms (between 7 and 205kDa). Few bands showed feeble caseinolytic, fibrinogenolytic and gelatinolytic activities by zymography, but strong hyaluronidase activity was observed in S. viridicornis and O. pradoi venoms. In addition, such activities could be inhibited by o-phenanthroline, indicating that these enzymes are metalloproteinases. All venoms induced nociception, edema and myotoxicity in mice, but only S. viridicornis induced mild hemorrhagic activity. No coagulant activity was detected in centipede venoms. Low phospholipase A(2) activity was observed exclusively in S. viridicornis and O. pradoi venoms, but these venoms had intense direct hemolytic activity on human erythrocytes. Cross-reactivity among venoms was observed using species-specific sera raised in rabbits. Differences were noticed among centipede venoms, but S. viridicornis is indeed the most toxic venom and thereby it could induce a more severe envenomation.
Assuntos
Venenos de Artrópodes/imunologia , Venenos de Artrópodes/toxicidade , Artrópodes/fisiologia , Animais , Antivenenos/metabolismo , Venenos de Artrópodes/química , Reações Cruzadas/efeitos dos fármacos , Reações Cruzadas/imunologia , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/patologia , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Hemorragia/induzido quimicamente , Hemorragia/patologia , Humanos , Metaloproteases/antagonistas & inibidores , Metaloproteases/metabolismo , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/enzimologia , Músculo Esquelético/fisiopatologia , Dor/induzido quimicamente , Dor/fisiopatologia , Medição da Dor , Fenantrolinas/farmacologia , Fosfolipases A/análise , Fosfolipases A/metabolismo , Coelhos , Pele/efeitos dos fármacos , Pele/patologiaRESUMO
Lines of mice genetically selected for high (H) or low (L) antibody response and for maximal (AIRMAX) or minimal (AIRMIN) acute inflammatory reaction, in which the opposite extreme potentialities have been clearly defined, offer an appropriate model for investigating the environmental and genetic factors acting on innate and adaptative immunobiological functions. This model has been successfully employed to study the resistance or susceptibility against pathogens and/or toxins. It had been demonstrated that the skin contact with Lonomia obliqua caterpillar bristles induces local inflammation and may elicit severe hemorrhagic disorders. In the present study, blood coagulation time, and the acute inflammatory reaction were scored 24 h after injection of the Lonomia bristles crude extract in a subcutaneous dorsal air pouch. The acute inflammation was determined by the leukocyte concentration in the local exudates. The highest interline differences were observed between the AIRMAX (10(6) cells/ml) and AIRMIN (2 x 10(5) cells/ml) and this distinct expression involves the number of monocytes, eosinophils and mainly neutrophils. Regarding coagulation, the highest interline difference was observed between the HIII and LIII mice, and the F1)[LIII x HIII] hybrids showed the overdominance of the fast clotting character. The adaptative immune response was evaluated by comparing the anti-Lonomia bristle extract IgG titer among the lines: the antibody titers were higher in the H lines than in the L ones and equivalent in the AIRMAX and AIRMIN mice, in accordance to the phenotype profiles generated by the distinct selective processes. The genetically selected mice lines-AIRMAX, AIRMIN, HI, HIII, HG, LIII and LG-showed an almost continuous distributions for inflammation, coagulation time and IgG antibody titers, being the interline variances always higher than the intraline ones for the individually measured phenotypes. Altogether, these results suggest the independent polygenic regulation of these traits, being indicative of the genetic control to Lonomia toxin innate and adaptative sensitivity in humans.
Assuntos
Venenos de Artrópodes/toxicidade , Imunização , Mariposas/química , Análise de Variância , Animais , Venenos de Artrópodes/imunologia , Coagulação Sanguínea/efeitos dos fármacos , Cruzamentos Genéticos , Ensaio de Imunoadsorção Enzimática , Granulócitos/efeitos dos fármacos , Imunoglobulina G/metabolismo , Inflamação/induzido quimicamente , Contagem de Leucócitos , Camundongos , Especificidade da EspécieRESUMO
To investigate the risk of life-threatening reactions to future stings, we sequentially challenged 113 children (aged 2 to 17 years) allergic to insect stings with a sting by the relevant insect. The time interval between the challenges varied from 2 to 6 weeks. The history of the index stings was a large local reaction (LR) in 16% and a systemic reaction (SR) in 84% of the test subjects. On the first challenge, 76% had a normal LR, 11% a large LR, and 13% an SR. On the second challenge, 78% of the children had a normal LR, 5% a large LR, and 17% an SR. Thirty-nine of the untreated children were exposed to a field sting during the subsequent 3-year follow-up period. In comparison with other diagnostic evaluations such as skin-prick tests, determinations of specific IgE and IgG antibodies, and single-sting exposure, the dual sting challenge scheme appears to be the best predictor of reactions to subsequent stings. It also appears to be helpful in selecting patients with an uncertain sensitization status for venom immunotherapy.
Assuntos
Himenópteros , Hipersensibilidade/diagnóstico , Mordeduras e Picadas de Insetos/diagnóstico , Adolescente , Animais , Venenos de Artrópodes/imunologia , Criança , Pré-Escolar , Dessensibilização Imunológica/métodos , Feminino , Seguimentos , Humanos , Hipersensibilidade/classificação , Hipersensibilidade/terapia , Imunoglobulina E/sangue , Mordeduras e Picadas de Insetos/classificação , Mordeduras e Picadas de Insetos/terapia , Masculino , Testes Cutâneos , Fatores de TempoRESUMO
The clinical dermal manifestations induced by hypersensitivity toward mosquito bites were studied in 50 patients of both sexes whose ages ranged between 0 and 15 years. Among 13 forms of lesions found papules and vesicles were the most frequent. A predominance of females when compared to other statistical data was evidenced. The correlation of these lesions with atopy is assessed, and pruritus, scratching and secondary infection are pointed out as factors worsening this state. Among sensitive subjects, skin tests using a 100 UNP concentration of the whole mosquito body extract were the most reliable.