Sensitivity to bee and wasp venoms: association with specific IgE responses to the bee and wasp venom and HLA DRB1 and DPB1

Background Stings from bees and wasps can cause systemic reactions which can be fatal in some individuals. In these venom-sensitive patients, specific IgE to the venom is produced and is considered to participate in the adverse reactions. This immune response requires antigen presentation by human leucocyte antigens (HLA) class II molecules, which includes DR and DP, which are present on antigen presenting cells. Objective To test for associations between HLA class II DRB1 and DPB1 alleles and life- threatening sensitivity to both bee and wasp venoms. To establish further whether any associations are independent of the atopy phenotype. Methods A total of 33 bee- and 44 wasp-venom-sensitive patients was studied. DRB1 genotypes were determined by single stranded oligonucleotide (SSO) probing of PCR products, and DPB1 genotypes by amplified fragment length polymorphism (AFLP) analysis. Total and specific IgE were measured using the Pharmacia Immunocap, FEIA. Patients with specific IgE to the venom antigens only were termed monosensitive and those with additional specific IgE to HDM and/or GP were termed polysensitive. Results Allele frequencies were compared to an unrelated control population. The 33 bee- sensitive patients had a greater prevalence of DRB 1*07 alleles than the control subjects, 26% vs 14%, with an odds ratio (OR) of 2.1 (95%CI, 1.2–3.7, P= 0.015, corrected for multiple comparisons, p_c > = ns). This association was confined to the 15 monosensitive bee patients, who had a 43% DRB 1*07 allele frequency when compared with 11% in the 18 polysensitive bee patients, OR 6.1 (95%CI, 1.73–22, P= 0.004, p_c= 0.05), and when compared with a control group of non-venom subjects, 43% vs 16%, OR 3.9 (95% CI, 1.72–9.0, P= 0.002, p_c= 0.02). The 44 wasp-sensitive patients had an increase in the DRB1*11 allele when compared with the control subjects, 13% vs 6%, with an OR 2.2 (95%CI, 1.0–4.6, P= 0.04, p_c= NS), and a decreased prevalence of DRB 1*04 alleles, 10% vs 19%, with an OR 0.33 (95%CI, 0.24–0.99, P= 0.04, p_c= NS), but these were not significant when multiple comparisons were taken into account. The DPB1 alleles were not significantly different between the venom sensitive patients and the controls. Conclusion Patients monosensitive to bee venom had a significantly greater prevalence of DRB 1 *07 alleles than the non-venom, control population suggesting that IgE responses in these patients may, in part be controlled by immune response HLA class II genes. These results are also suggestive of wasp-sensitive patients having a higher prevalence of DRB1*11 and a lower prevalence of DRB 1*04 than the control population.     

Paulistine—The Functional Duality of a Wasp Venom Peptide Toxin

It has been reported that Paulistine in the venom of the wasp Polybia paulista co-exists as two different forms: an oxidized form presenting a compact structure due to the presence of a disulfide bridge, which causes inflammation through an apparent interaction with receptors in the 5-lipoxygenase pathway, and a naturally reduced form (without the disulfide bridge) that exists in a linear conformation and which also causes hyperalgesia and acts in the cyclooxygenase type II pathway. The reduced peptide was acetamidomethylated (Acm-Paulistine) to stabilize this form, and it still maintained its typical inflammatory activity. Oxidized Paulistine docks onto PGHS2 (COX-2) molecules, blocking the access of oxygen to the heme group and inhibiting the inflammatory activity of Acm-Paulistine in the cyclooxygenase type II pathway. Docking simulations revealed that the site of the docking of Paulistine within the PGHS2 molecule is unusual among commercial inhibitors of the enzyme, with an affinity potentially much higher than those observed for traditional anti-inflammatory drugs. Therefore, Paulistine causes inflammatory activity at the level of the 5-lipooxygenase pathway and, in parallel, it competes with its reduced form in relation to the activation of the cyclooxygenase pathway. Thus, while the reduced Paulistine causes inflammation, its oxidized form is a potent inhibitor of this activity.     

Acute tubulointerstitial nephritis after wasp stings

A 61-year-old Caucasian man presented with acute renal failure after multiple wasp stings. The patient required dialysis support temporarily. Work-up failed to show rhabdomyolysis or hemolysis and a kidney biopsy revealed acute allergic interstitial nephritis. The patient's renal function recovered completely after a short course of steroid therapy. Acute renal failure after wasp stings is typically caused by acute tubular necrosis in the setting of hemolysis or rhabdomyolysis. Compared with previously reported cases of acute renal failure associated with bee stings, our patient is unique in that his renal failure was caused by a hypersensitivity reaction apparently to the wasp venom. © 2001 by the National Kidney Foundation, Inc.     

Engineering Venom’s Toxin-Neutralizing Antibody Fragments and Its Therapeutic Potential

Serum therapy remains the only specific treatment against envenoming, but anti-venoms are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum. Most of these anti-venoms are considered to be efficient, but their production is tedious, and their use may be associated with adverse effects. Recombinant antibodies and smaller functional units are now emerging as credible alternatives and constitute a source of still unexploited biomolecules capable of neutralizing venoms. This review will be a walk through the technologies that have recently been applied leading to novel antibody formats with better properties in terms of homogeneity, specific activity and possible safety.     

Report of the 4th international conference on envenomations by snakebites and scorpion stings in Africa, Dakar, April 25–29, 2011

The authors present a summary of the proceedings and the recommendations of the the 4th International Conference on Envenomations by Snakebites and Scorpion Stings in Africa, held from April 25th to 29th in Dakar. After a two day training workshop for Senegalese health personnel on the most relevant aspects of the management of envenomations, about 270 participants met to share their experiences in the field. Nearly a hundred oral and poster contributions concerning the epidemiology of snakebites and scorpion stings in Africa, the composition and action of venoms, as well as the manufacture and use of antivenoms, were presented and discussed. The last day was devoted to an institutional debate joining experts, representatives of national health authorities and concerned professionals (physicians, pharmacists, nurses and traditional healers) as well as members of the pharmaceutical industry, to discuss and elaborate a set of recommendations. It was agreed that it is necessary to improve knowledge of the epidemiological situation by case reporting. Quality control of anivenoms and procedures for their registration at the level of national health authorities should aim at improving the distribution of safe and effective antivenoms in peripheral health centers, which bear the heaviest burden of cases. It was also recommended that adequate training of health personnel in all aspects of medical management of envenomations should constitute a priority. Finally, financing mechanisms to ensure an equitable distribution of resources must be sought, as well as the constitution of a network of African experts were discussed at length.     

重症胡蜂蜇伤致溶血、多器官功能衰竭的救治体会

【】 目的 总结重症胡蜂蜇伤的成功救治经验,探索蜂毒中毒新的救治方法。 方法 分析我院被同一宗胡蜂蜇伤的2例重症患者,其中一例被蜇伤252针,另一例被蜇伤246针,入院时,均已出现溶血、多脏器功能衰竭。通过杂合式血液净化,局部外敷季德胜蛇药片及蜂蜇草,对症支持等综合治疗,患者溶血得到有效控制,脏器功能逐渐恢复。 结果 一例患者逐渐好转,住院16日后出院;另一患者迅速好转,两日后出院。出院后,电话随访,患者均已痊愈。 结论 杂合式血液净化能有效清除体内蜂毒,保护重要脏器功能,促进受损器官恢复;季德胜蛇药片与蜂蜇草可能有一定的解毒功效,有待进一步研究。     

Unconscious Woman in Shock and Covered with Ants Pulled from an Abandoned Automobile

BackgroundA middle-aged woman was taken from an abandoned automobile unconscious and covered with ants in Tucson, Arizona. When hospitalized in July 2018, she had an extensive papular-pustular skin eruption on her abdomen and thigh and disseminated intravascular coagulation. She was stung innumerable times by native golden fire ants (Solenopsis aurea) while sleeping in the vehicle. The large amount of venom injected by stings into this individual may have triggered dissemnated intravascualar coagulation because the venom contains powerful hemolytic factors.MethodsThe patient history is presented and ants were captured and identified.ResultsClinical findings of fire ant stings are presented and the importance of recognizing the distinctive skin lesions that occur is emphasized. Stings of the red imported fire ant, Solenopsis invicta, and the black imported fire ant, Solenopsis richteri, cause skin lesions recognized by physicians and victims alike in the southern and southeastern United States. Native fire ant stings are documented much less often. However, there is significant cross-reactivity among the venoms of Solenopsis species.ConclusionIt is important for clinicians to recognize the characteristic skin lesions of fire ant envenomation as fire ant populations are expanding and they sting millions of people each year.     

蚂蚁叮蜇伤56例临床分析

目的总结蚂蚁叮蜇伤的临床表现、实验室检查、诊断和治疗,提高对蚂蚁叮蜇伤的认识。方法对2005年4月—2009年7月收集的56例蚂蚁叮蜇伤患者的临床资料进行回顾性分析。结果单纯荨麻疹型（皮肤型）21例;复杂荨麻疹型35例,其中休克23例、严重心律失常5例、Ⅲ度和Ⅳ度喉阻塞各1例。治疗以糖皮质激素为主,辅以相应的抢救措施,56例均治愈。结论蚂蚁毒素刺激机体免疫系统引起免疫功能紊乱,局部组织坏死、溶血,促使肥大细胞释放组胺和血管活性胺类物质,引起细胞坏死,触发Ⅰ型变态反应、全身炎症反应综合征,导致微循环障碍、休克。经及时内科综合治疗预后良好。     

Defining the T cell antigen proteome of wasp venom

BACKGROUND: While modulation of T cell function is believed to be important in the successful acquisition of clinical tolerance during venom immunotherapy, little is known of the role of wasp venom specific T cell antigens. OBJECTIVE: We sought comprehensively to characterize the T cell proteome for wasp venom to facilitate the future development of T cell-based immunotherapeutic approaches. METHODS: Using peripheral blood mononuclear cells from wasp venom-allergic individuals and IL-4 ELISPOT analysis, we characterized T cell responses to whole venom and gel filtration/ion exchange-fractionated venom. Reactive fractions were purified and identified using highly sensitive electrospray ion-trap mass spectrometry. RESULTS: Wasp venom-allergic individuals have detectable whole wasp venom-specific T cells directly ex vivo, which show rapid IL-4 effector function. T cell responses to gel filtration/ion exchange fractionated venom were dominated by responses to phospholipase A(1), hyaluronidase and antigen 5. CONCLUSION: Although it is likely that there are many T cell antigens within wasp venom, the main responses are to proteins coincident with the known IgE-binding proteins.