John E. Moffitt

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)

Increased frequency of large local reactions among systemic reactors during subcutaneous allergen immunotherapy

BACKGROUND Large local reactions are not uncommon during allergen immunotherapy (AIT). Dosage adjustments after large local reactions are commonly instituted despite literature that suggests individual large local reactions do not seem to predict subsequent systemic reactions. OBJECTIVE To investigate the relationship between large local reactions and the risk of systemic reactions to AIT. METHODS Retrospective review of the AIT database of a large, multicenter allergy practice group was conducted between June 1, 2003, and May 31, 2005. Numbers of large local reactions in 258 patients who experienced systemic reactions to AIT were compared with 299 age-, sex-, and sensitivity-matched control patients who did not experience systemic reactions during AIT. RESULTS A total of 283 systemic reactions occurred in 258 patients during the surveillance period, which included 661,123 patient visits for 1,108,621 allergy injections. The systemic reaction rate was 0.043% of visits and 0.025% of injections. The large local reaction rate was 35.2% of visits and 19.5% of injections among systemic reactors compared with 8.9% of visits and 5.3% of injections in the controls (P < .001 each). Thus, the odds of experiencing large local reactions were significantly increased among systemic reactors. CONCLUSIONS Although AIT is a safe and effective immunomodulatory therapeutic option for the treatment of allergic diseases, patients with increased frequency of large local reactions may have increased risk for future systemic reactions. Identifying additional risk factors remains viable. Recognizing the relevance of frequent large local reactions is important for designing safer protocols for successful AIT in these patients.

Fire Ant Venom Alkaloid, Isosolenopsin A, a Potent and Selective Inhibitor of Neuronal Nitric Oxide Synthase

Massive, multiple fire ant, Solenopsis invicta, stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown. To assess a possible pharmacological basis for systemic toxicity, an alkaloid-rich, protein-free methanol extract of the venom from whole ants was assayed for inhibitory activity on the following nitric oxide synthase (NOS) isoforms, rat cerebellar neuronal (n NOS), bovine recombinant endothelial (e NOS), and murine recombinant immunologic (i NOS). Cytosolic NOS activity was determined by measuring the conversion of [3H]arginine to [3H]citrulline in vitro. Rat n NOS activity was inhibited significantly and in a concentration-dependent manner by the alkaloid-rich venom extract. For n NOS, enzyme activity was inhibited by approximately 50% with 0.33 ± 0.06 μgg of this venom extract, and over 95% inhibition of the three isoforms, n NOS, e NOS, and i NOS, was found with doses of 60 μg in 60-μl reaction mixture. These results indicate that the alkaloid components of S. invicta venom can produce potent inhibition of all three major NOS isoforms. Isosolenopsin A (cis-2-methyl-6-undecylpiperidine), a naturally occurring fire ant piperidine alkaloid, was synthesized and tested for inhibitory activity against the three NOS isoforms. Enzyme activities for n NOS and e NOS were over 95% inhibited with 1000 μM of isosolenopsin A, whereas the activity of i NOS was inhibited by only about 20% at the same concentration. The IC50 for each of three NOS isoforms was approximately 18 ± 3.9 μM for n NOS, 156 ± 10 μM for e NOS, and >1000 μM for i NOS, respectively. Kinetic studies showed isosolenopsin A inhibition to be noncompetitive with L-arginine (Ki = 19 ± 2 μM). The potency of isosolenopsin A as an inhibitor of n NOS compares favorably with the inhibitory potency of widely used n NOS inhibitors. Inhibition of NOS isoforms by isosolenopsin A and structurally similar compounds may have toxicological significance with respect to adverse reactions to fire ant stings.

Allergic reactions to Triatoma bites

BACKGROUND Triatoma bugs are best known in the medical community as vectors of trypanosomiasis (Chagas disease). However, bites of Triatoma bugs are a cause of local cutaneous reactions and anaphylaxis, mainly in the western and southwestern United States. The reactions typically occur at night during sleep, and the bite may not be recognized. There is continuing public interest in medical complications of bites of these bugs, although the scope of the problem remains undefined. OBJECTIVE To review the relevant medical literature, identify present knowledge, and determine future research goals for allergy to Triatoma. DATA SOURCES Computerized databases were used to search the medical literature for articles in the English language on Triatoma bites, allergy and entomology, and Chagas disease. STUDY SELECTION Almost all identified articles on Triatoma allergy were used. Only selected articles on Triatoma bites and entomology were pertinent to the objectives. Articles on Chagas disease were limited to cases in the United States. RESULTS Bites of Triatoma bugs have been known to cause anaphylaxis for more than a century. These insects inhabit a large area of the United States, but to date most reports of allergic reactions to their bites have originated in the West and Southwest. The reactions typically occur at night during sleep following a bite on uncovered skin and may be unrecognized. Procalin has been identified as the major salivary allergen of Triatoma protracta and was recently cloned and expressed through recombinant technique. Allergenic reactivity has been demonstrated to salivary gland extracts of 2 species. The extracts of these 2 species have not shown immunologic cross-reactivity. Immunotherapy using a salivary gland extract appeared to be beneficial in a small number of patients; however, no commercial testing or treatment allergen is available. CONCLUSIONS Triatoma bites appear to be an important cause of anaphylaxis, especially in the western and southwestern United States. Because exposure to these insects often occurs during sleep, the incidence of allergic reactions to them is unclear. An epidemiologic study should be performed to determine the incidence, prevalence, and range of allergic responses to the bites of these insects. The lack of commercial antigen limits diagnostic and treatment capabilities. The development of an allergen under the Orphan Drug Act should be encouraged.

Allergens in Hymenoptera venom. XXII. Comparison of venoms from two species of imported fire ants, Solenopsis invicta and richteri

Venoms were collected by electrical stimulation from the two major species of imported fire ants found in the United States, Solenopsis invicta (Sol i) and S. richteri (Sol r). Antigens similar to three of the four known Sol i venom proteins (I, II, III, and IV) were isolated from Sol r. The N-terminal amino acid sequences for the antigens III were identical; but those for the antigens II demonstrated only nine of 20 residues to be identical. Two monoclonal antibodies raised against Sol i II did not react to Sol r. No protein IV could be detected in Sol r by molecular weight, charge, or immunologically with either polyclonal mouse antibodies or five monoclonal antibodies. Both venoms were compared with a panel of 60 sera from Sol i-allergic individuals; mean bindings were similar with an r = 0.94 for linear regression. RAST inhibition was performed with 17 individual sera representing a variety of Sol i allergen specificities. Four sera were tested from patients resident in the Sol r endemic area and five sera from patients who experienced reactions to S. xyloni stings. All sera reacted comparably to both imported fire ant venoms. The two venoms appear to be allergenically similar, although antigen IV is absent from Sol r and the antigens II have significant sequence variation. Sol i venom appears to be sufficient for diagnostic purposes.

Management of imported fire ant allergy : results of a survey

BACKGROUND Fire ant allergy is a significant health problem in the southern United States. Management of fire ant allergy is less clearly defined than management of allergy to the winged Hymenoptera. OBJECTIVE To determine how fire ant allergy is managed by practicing allergists. METHODS A survey form was developed and distributed to American College of Allergy, Asthma & Immunology members practicing in fire ant endemic states. Completed forms were returned to the American College of Allergy, Asthma & Immunology central office and forwarded to the authors for analysis. RESULTS Three hundred twenty-nine of 879 (37.4%) surveys were returned; 81% of respondents have evaluated patients with imported fire ant allergy. Immunotherapy is used by 96.7% of respondents to treat fire ant allergy. A wide range of maintenance dosages are prescribed. Skin testing is the most common diagnostic method. Systemic reactions to stings while on maintenance immunotherapy were reported by 19%. Allergists utilize different criteria in consideration for stopping immunotherapy; 19% continue it indefinitely. CONCLUSIONS There are many areas of general uniformity and other areas of divergence in how allergists manage imported fire ant allergy. These findings suggest continued need for further investigation regarding the efficacy, dosage, and duration of immunotherapy, as well as further elucidation of the natural history of fire ant allergy.

Candida endocarditis in a child with hyperimmunoglobulinemia E syndrome

Hyperimmunoglobulin E syndrome (HIE) is a disorder characterized by extremely elevated serum levels of IgE and recurrent infections. Patients are particularly predisposed to have staphylococcal abscesses, usually involving skin, lungs, and joints; but they are also at risk for infections with other bacteria and fungi. We report the case of a 46-month-old boy with HIE who had Candida endocarditis and sepsis with a large fungal mass extending through the tricuspid valve and into the surrounding heart tissue, requiring surgical excision and replacement with a prosthetic valve. He had an indwelling central line for previous antibiotic therapy and had oral thrush for a month before presentation, which had been treated with oral nystatin. He was first seen with very dark urine, a new murmur, petechial rash, in shock, and disseminated intravascular coagulation. The white blood cell count was 38,700 with 70% segmented neutrophils, 9% banded neutrophils, 15% lymphocytes, 4% monocytes, and 2% eosinophils. Hemoglobin was 7.1, and platelet count was 14,000. Prothrombin time was 15.5, and partial thromboplastin time was 31; fibrinogen level was 110 mg/ml, and fibrin degradation products were greater than 40 mg/ml. Serum IgE was 38,664 and 44,510 on repeat measurement. He has had recurrent staphylococcal pneumonias with pneumatoceles, twice requiring segmental lung resection. Blood and tricuspid valve cultures grew Candida albicans. He was treated with amphotericin and flucytosine, and later switched to fluconazole, with good response to therapy. A literature search revealed no other reported case of Candida endocarditis in patients with HIE. Fungai endocarditis is a rare complication, which may occur in patients with HIE and indwelling central catheters.

Comparison of acellular (B type) and whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines as the first booster immunization in 15-to 24-month-old children

We compared an acellular (B type) pertussis-component diphtheria-tetanus-pertussis (DTP-Ac) vaccine containing equal amounts of filamentous hemagglutinin and lymphocytosis-promoting factor with a conventional whole-cell vaccine as the first booster immunization in 162 healthy children 15 to 24 months of age. Fewer local reactions (e.g., erythema, swelling, and tenderness at the injection site) were seen in DTP-Ac vaccine recipients during the first 48 hours of observation. This group also had fewer episodes of fever (> or = 38 degrees C) and other systemic reactions (e.g., irritability, drowsiness, and anorexia). Overall, 57% of the DTP-Ac vaccine recipients had no obvious adverse reactions, in contrast to 5% in the comparison group. At 4 to 8 weeks after vaccination, serum antibody responses to filamentous hemagglutinin and lymphocytosis-promoting factor were greater in recipients of the acellular vaccine as determined by an enzyme-linked immunosorbent assay. We conclude that this B-type acellular vaccine is both immunogenic and much less likely to cause an adverse reaction than a currently licensed whole-cell vaccine, and is suitable for routine booster immunizing doses to protect against pertussis.

Type I diabetes in an adolescent with common variable immunodeficiency

A male adolescent with common variable immunodeficiency developed type I diabetes approximately 1 year after the initiation of immunoglobulin therapy. Immunologic evaluation revealed decreased numbers of T cells and an intrinsic B cell defect in immunoglobulin production. Lymphocytes from the patient failed to generate normal suppressor activity. There were no insulin or islet cell antibodies present in the patients serum or in the commercial immunoglobulin preparations he received. The patients HLA phenotype included HLA-DR3 and 4, placing him genetically at high risk for type I diabetes.

ALLERGY TO INSECT STINGS : A NEED FOR IMPROVED PREVENTIVE MANAGEMENT

Allergy to insect venom is a major health problem for a significant number of people. Immunotherapy can reduce the risk of subsequent reaction from about 60% to less than 5%. Standard preventive care should include (1) advice concerning avoidance of insects, (2) prescription of an epinephrine kit or syringe for self-administration (unless medically contraindicated), and (3) referral for evaluation. Results of several studies from various regions of the country raise concern about the preventive care and advice given these patients and suggest a need for continuing medical education to improve preventive management of allergy to insect stings.