Wasp venom immunotherapy induces a shift from IL-4-producing towards interferon-gamma-producing CD4+ and CD8+ T lymphocytes

BACKGROUND: Venom immunotherapy (VIT) has proven to be very effective in hymenoptera venom anaphylaxis. However, the underlying immunoregulatory mechanisms of venom immunotherapy remain poorly understood. Recent studies measured the total amount of cytokine in culture supernatans, suggesting a shift in cytokine production from Th2 to a Th1 cytokine profile during VIT. We wanted to examine the contribution of specific T lymphocyte subpopulations, which is impossible using an extracellular method to determine cytokines in supernatants. OBJECTIVE: The present study was designed to evaluate the effect of VIT on the percentages of type 1 (IL-2, interferon-gamma (IFN-gamma)) and type 2 (IL-4) CD4+ and CD8+ T lymphocytes of patients with wasp venom anaphylaxis during immunotherapy. METHODS: Peripheral blood mononuclear cells of 20 individuals with a history of wasp sting anaphylaxis and a positive serum wasp venom specific IgE were isolated and in vitro stimulated with phorbol-12-myristate-13-acetate and ionomycin before VIT, at the end of a 5-day semirush VIT and at 6 months during VIT. Three-colour flow cytometric analysis was used for intracellular cytokine (IL-2, IFN-gamma, IL-4) detection in CD4+ (CD3+CD8-) T lymphocytes and CD8+ (CD3+CD8+) T lymphocytes. RESULTS: At the end of a 5-day semirush VIT, there was a significant decrease in percentage of IL-4-producing CD4+ and CD8+ T cells, compared with cytokine-producing cells before VIT (P = 0.0002 and 0.004). After 6 months of VIT, patients showed an increased number of IL-2-producing stimulated CD4+ and CD8+ lymphocytes compared with values before VIT (P = 0.002 and P = 0.0003). A higher amount of IFN-gamma-producing stimulated CD4+ and CD8+ cells was found after 6 months of VIT (P = 0.001 and P = 0.0006). There was no correlation between cytokine-producing cells and specific IgE for wasp. CONCLUSION: Venom immunotherapy induced a shift from IL-4-producing towards IFN-gamma-producing CD4+ as well as CD8+ T lymphocytes.     

Efficacy and Safety of Allergen-Specific Immunotherapy in Rhinitis,Rhinoconjunctivitis, and Bee/Wasp Venom Allergies

The prevalence of allergic diseases, such as rhinoconjunctivitis, is increasing worldwide, particularly in Westernized countries, where more than 30% of the population is affected. Insect venom allergy is also very common, affecting up to 5% of the population. Allergen-specific immunotherapy is the only immunomodulatory treatment that may alter the natural course of allergic disease, for example by preventing the development of asthma in rhinitic patients. Nonetheless, the risk-benefit ratio for subcutaneous immunotherapy has changed little from when it was first developed a century ago. However, the rapid evolution of new developments, including new methods of administration and new forms of antigen to stimulate the immune system, now offers improvements in both the safety and the efficacy of specific immunotherapy. These developments include the sublingual administration of the relevant antigens, which has a superior safety profile than the original subcutaneous route. This may enable higher dosages to be used over shorter treatment periods, with a lower risk of anaphylactic reactions. Improvements in the purity, specificity, and immunogenicity of the antigens, often as a result of advances in biotechnology, coupled with the development of new adjuvants, may further increase the efficacy of this form of treatment. This review describes and discusses these new developments in the context of the many recent advances in our understanding of the mechanisms by which immunotherapy appears to act.     

Component-resolved diagnosis in hymenoptera allergy

Component-resolved diagnosis based on the use of well-defined, properly characterised and purified natural and recombinant allergens constitutes a new approach in the diagnosis of venom allergy. Prospective readers may benefit from an up-to-date review on the allergens. The best characterised venom is that of Apis mellifera, whose main allergens are phospholipase A2 (Api m1), hyaluronidase (Api m2) and melittin (Api m4). Additionally, in recent years, new allergens of Vespula vulgaris have been identified and include phospholipase A1 (Ves v1), hyaluronidase (Ves v2) and antigen 5 (Ves v5). Polistes species are becoming an increasing cause of allergy in Europe, although only few allergens have been identified in this venom.In this review, we evaluate the current knowledge about molecular diagnosis in hymenoptera venom allergy.     

Insect Allergy

One hundred and seventeen persons all stung by yellow jacket (YJ) and/or bee were examined by means of skin prick test with venom of these insects, skin prick test with 10 inhalant allergens and analyses of total IgE. Specific IgE and IgG against honey bee and YJ venom. Eighty-seven persons had had a systemic reaction. Positive correlations ( P < 0.05) were found between results of skin prick tests and specific IgE against venoms and, for YJ, between the severity of symptoms after sting and the size of skin prick test with the venom. That some of the more severe symptoms could have been caused by non-immunological mechanisms could explain why a significant correlation was present only between the results of the prick test and specific IgE and not between these tests and the clinical symptoms. Specific IgE values against YJ and honey bee venom showed convariation, although no correlation could be demonstrated between the clinical symptoms after stings from these insects, or between skin prick test results using the two different extracts. The severity of the sting reactions was not correlated to age, atopic disposition, amount of total IgE, number of stings during life, or positive skin prick test to inhalant allergens. It is concluded that in insect allergy, specific IgE analysis and skin prick tests are supplementary.     

Scrotal dog bites

PURPOSE: Dog bites to the scrotum are rare but they potentially result in morbidity if improperly managed. MATERIALS AND METHODS: Between 1991 and 1999 we treated 4 men and 3 boys with dog bites to the scrotum. All 7 patients presented to the emergency department shortly after the injury. Of the 4 adults 3 were ingesting alcohol and 2 were obviously intoxicated, and 1 had a T4 spinal cord injury and was bitten during sleep. Of the children 2 were apparently bitten without provocation, while a 5-year-old boy was bitten when the family dog was disturbed while eating. RESULTS: All wounds were explored, irrigated and débrided. There was no involvement of the testes or spermatic cord. Each wound was closed primarily and 5 healed without sequelae. The spinal cord injured man had partial dehiscence of the incision and in another man superficial hematoma required drainage. Each patient received antibiotics and tetanus prophylaxis but none required rabies inoculation. CONCLUSIONS: Although there are reports of devastating scrotal injuries from dog bites, most such wounds may be treated by careful inspection for intrascrotal injuries followed by débridement and closure. Antimicrobial prophylaxis should be administered, as for any bite wound.     

The excision of polydnavirus sequences from the genome of the wasp Cotesia congregata (Braconidae, Microgastrinae) is developmentally regulated but not strictly restricted to the ovaries in the adult

Cotesia congregata polydnavirus (CcPDV) is essential for the successful parasitism of Manduca sexta larvae by the braconid wasp Cotesia congregata. In the absence of PDV, parasitoid eggs are encapsulated. Molecular analysis has demonstrated that polydnavirus sequences are integrated in the wasp chromosomes, and an ultrastructural analysis has shown that PDV replication occurs in the calyx region in the ovaries of the wasp. The bracovirus sequences appear to be excised from the wasp genome in the calyx cells where the virus replicates. Following excision of the virus sequences, the flanking sequences are rejoined. We analysed the production of two polydnavirus circles during wasp development and in different body parts of the adults of both sexes. Our study indicates that the excision of viral sequences is developmentally regulated, beginning in the pupal stage. In the adult wasp, excision occurs ubiquitously. However, regulation in the adult seems to occur only in diploid individuals, as no excision is detected in haploid males produced from virgin females.     

急诊毒虫叮咬伤的临床特点及救治分析

目的总结毒虫叮咬伤的种类、临床特点和治疗效果。方法对1997年4月—2007年10月急诊处理的3250例毒虫叮咬伤患者的临床资料和中西医治疗效果进行总结分析。结果毒虫叮咬伤主要包括蝎子伤(33·4%)和毒蚊伤(28·9%)等;受伤部位主要为四肢(71·4%)和头面部(14·0%);主要症状有局部反应、全身症状和严重并发症。叮咬后在急诊根据其分类进行中西医结合处理,均预后良好,但对过敏体质者要留观处理。结论根据毒虫叮咬伤的受伤种类和相应症状采用中西医结合疗法进行处理效果好,适用于各基层单位。     

Australian scorpion stings: a prospective study of definite stings.

There is little information on scorpion stings in Australia. The aim of this study is to describe the circumstances and clinical effects of stings by Australian scorpions. Cases of scorpion stings were collected prospectively from calls and presentations to Australian poison information centres and emergency departments from February 2000 to April 2002. Only definite scorpion stings where the scorpion was immediately collected and expertly identified were included. There were 95 patients, 33 males and 62 females, with a mean age of 32 (SD 19.5; range 1-71) and 23 children (age<15 years). Three families of scorpions caused all stings: Buthidae (79), Bothruiridae (11, all Cercophonius spp.) and Urodacidae (five, all Urodacus spp.). The majority of stings (76%) were by one genus of scorpion Lychas spp. Seventy one percent of stings occurred between 6pm and 8am and 82 (86%) occurred indoors. Sixty percent of stings occurred on distal limbs. The median duration of effects was 6 h (interquartile range (IQR): 1-24 h). Immediate localised pain occurred in all cases and was severe in 76 cases (80%). Other local effects included red mark/redness (66%), tenderness (35%), numbness (12%) and paraesthesia (11%). Minor systemic effects (nausea, headache and malaise) occurred in 11% of cases. There were no deaths or major systemic envenoming. Less severe effects were observed for the larger Urodacus species, compared to Lychas spp. Scorpion stings in Australia do not appear to cause severe or life-threatening effects, even in children. This differs from other parts of the world, where severe envenoming is reported. The major clinical effect is severe pain, consistent with other scorpion stings. Most stings occurred indoors and at night.