The clinical spectrum of omega-5-gliadin allergy.

BACKGROUND: IgE-mediated allergy to the wheat protein omega-5-gliadin (O5G) is associated with wheat-dependent exercise-induced anaphylaxis (WDEIA), where exercise acts as a cofactor, triggering anaphylaxis after wheat ingestion. The wider application of O5G-specific IgE (sIgE) testing has revealed that the manifestations of O5G allergy extend beyond WDEIA. AIMS: This study documents clinical manifestations in a large series of patients with sIgE to O5G. METHODS: A retrospective clinical audit was performed on adult patients with a positive O5G sIgE (>0.35kU/L) between 2007 and 2013 compared with a group who had negative O5G sIgE. Clinical characteristics and skin prick test (SPT) results were examined. RESULTS: Sixty-seven patients were characterised, 26 of whom presented with food-dependent exercise-induced allergy, whilst others presented with exercise-induced symptoms without apparent food association (16/67), idiopathic anaphylaxis (10/67), food-induced allergic symptoms without exercise (10/67) or recurrent acute urticaria (5/67). Specific IgE to O5G had 91% sensitivity and 92% specificity for wheat-related allergic symptoms. SPT had sensitivity of 92% and specificity of 84%. CONCLUSION: WDEIA is the most common manifestation of O5G allergy, but patients may present with a variety of allergic manifestations, and wheat allergy is not always obvious on history. Non-exercise cofactors or a lack of cofactors were identified in many patients. A distinctive feature of this allergy is that despite regular wheat ingestion, allergic reactions to wheat occur infrequently. Testing for sIgE to O5G should be considered in patients presenting with exercise-induced urticaria/anaphylaxis, idiopathic anaphylaxis and recurrent acute (but not chronic) urticaria.

Increased intestinal permeability in atopic eczema.

We have investigated gastrointestinal permeability in children with atopic eczema by measuring the relative urinary excretion rates of the inert di- and monosaccharides lactulose and rhamnose following their oral administration. The median lactulose/rhamnose ratio was greater in 26 children with atopic eczema than in a control group of 29 children which included both healthy individuals and others with various noneczematous dermatoses. This increased permeability may be a primary abnormality of the gut or may reflect intestinal mucosal damage caused by local hypersensitivity reactions to food antigens.

Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation.

OBJECTIVES: To assess a protocol for treatment of sting anaphylaxis. DESIGN: Prospective assessment of treatment with oxygen, intravenous infusion of adrenaline (epinephrine), and volume resuscitation with normal saline. SETTING: Sub-study of a venom immunotherapy trial. PARTICIPANTS: 21 otherwise healthy adults with systemic allergic reactions to diagnostic sting challenge. MAIN OUTCOME MEASURES: Response to treatment, total adrenaline dose and infusion duration, recurrence of symptoms after stopping the infusion, and additional volume resuscitation. RESULTS: 19 participants required intervention according to the protocol. All received adrenaline, and five received volume resuscitation. In nine cases, physical signs of anaphylaxis recurred after initial attempts at stopping adrenaline but resolved after recommencing the infusion. The median total dose and infusion duration were 590 micro g and 115 minutes respectively, but were significantly higher for eight patients who had hypotensive reactions (762 micro g and 169 minutes respectively). Hypotension was always accompanied by a relative bradycardia, which was severe and treated with atropine in two patients. Widespread T wave inversion occurred, before starting treatment with adrenaline, in one person with an otherwise mild reaction. All patients fully recovered and were fit for same day discharge, apart from the person with ECG changes who was observed overnight and discharged the following day. CONCLUSIONS: Carefully titrated intravenous adrenaline combined with volume resuscitation is an effective strategy for treating sting anaphylaxis, however severe bradycardia may benefit from additional treatment with atropine. Cardiac effects of anaphylaxis, perhaps including neurocardiogenic mechanisms, may be an important factor in some lethal reactions.

Bee venom hypersensitivity and its management: patients perception of venom desensitisation.

The objectives of the study were to review bee venom immunotherapy from the patient's perspective: in particular its benefits and its problems, and to investigate any genetic tendency for bee venom hypersensitivity. A self administered, 9 item questionnaire was sent to 219 patients who had undergone either inpatient or outpatient bee venom immunotherapy at Flinders Medical Center. The clinic records of these patients were also reviewed. The controls for the genetic study were sought from patients, staff and students at Flinders University and Flinders Medical Centre. One hundred and forty-six questionnaires (some incomplete and anonymous) were received. The female to male ratio was 1:2.5. The age at the time of the initial anaphylactic reaction to a bee sting ranged between 2 to 59 years, with 67% of patients being less then 20 years old. Forty percent of patients underwent venom immunotherapy for a period less than 2 years with only 11% maintaining therapy for the recommended period of 5 years or more. Thirty three percent of patients stopped their therapy on their own accord. Bee stings occurring during bee venom immunotherapy (n = 56) were generally well tolerated except in 8 subjects, 7 of whom had not reached the maintenance dose. The reduction in systemic reactions to subsequent bee stings was significantly better in the study group receiving bee venom than in an historic control group treated with whole bee extract (p = 0.03). Fear of bee stings and restricted life styles were improved during or after venom immunotherapy. The frequency of a positive family history of systemic reactions to bee stings in the patient cohort was 31%, whereas in controls it was 15% (p = 0.013). Bee venom immunotherapy has dual benefits: patients are protected from subsequent sting anaphylaxis and there is reduced psychological morbidity. However, to be effective, venom immunotherapy requires a prolonged period of carefully supervised treatment and each venom injection can cause local and systemic side effects. Genetic factors appear to be present in those patients who develop immediate hypersensitivity to be stings.

Immunoblot analysis of IgE and IgG antibodies to honey bee venom: cross sectional and sequential studies in bee sensitive subjects.

To investigate the specific IgE and IgG immune response to honey bee venom (bv), we performed immunoblot analysis of sera from 47 bee sensitive subjects and followed the response during and after venom immunotherapy in 15 of these subjects. Fifteen venom proteins varying in molecular size from 20 to 105 kDa were identified as being antigenic and consisted of a high molecular weight (HMW) group (5 to 105 kDa, containing the previously identified allergens B and C) and a low molecular weight group (LMW) containing hyaluronidase and phospholipase A. In general for a given individual the anti-venom IgE and IgG response was qualitatively similar although some variation between individuals was apparent. Reactivity with hyaluronidase and phospholipase A appeared only in those subjects showing reactivity with HMW components. During immunotherapy specific anti-venom IgG and IgE responses tended to be linked. Increased responses being seen against all components in 4 of 12 subjects, reductions in 3 and unchanged responses in the remainder. Following immunotherapy (mean 4.0 years), spontaneous reduction of IgE and IgG was seen in 5 of 5 subjects. Loss of reactivity with the LMW components was prominent in these sera.

Bee sting anaphylaxis in an urban population of South Australia.

The clinical manifestations and circumstances of bee sting anaphylaxis have been studied retrospectively in 98 subjects. Most reactions occurred in children but the most severe reactions were seen in adult males, of whom 7 lost consciousness and 2 required cardiopulmonary resuscitation. Most stings causing anaphylaxis occurred on the unprotected feet whilst the subject was on lawn in the afternoons in December, January and February when the maximum daily temperature was between 20 and 30 degrees C. This is the temperature range when bees are particularly active in gathering pollen. However, a significantly greater frequency of anaphylactic reactions occurred at higher temperatures when bees are less active, suggesting that high environmental temperature may predispose the individual to greater exposure to bees or possibly to anaphylactic reactions per se. The presence of atopy did not appear to predispose subjects to bee venom hypersensitivity. Considerable anxiety and lifestyle alteration were identified in some subjects. The alleviation of this anxiety is considered an appropriate indication for bee venom immunotherapy.

Common allergic skin conditions.

Skin conditions regarded as having an 'allergic' origin are extremely common. Immunologically specific hypersensitivities to food and aeroallergens and idiosyncratic reactions to food chemicals play a role in some of the individuals suffering from these conditions, but in others intrinsic or unknown factors dominate. Rashes are frequently seen in relation to food intolerance and adverse drug reactions that share common mechanisms.

A patient with anaphylaxis after alteplase infusion.

Anaphylaxis to alteplase is a rare but reported complication of intravenous thrombolysis. We report a patient with a documented episode of anaphylaxis that occurred following an initial bolus and a subsequent delayed infusion of alteplase for thrombolysis of acute ischaemic stroke. The patient was treated with hydrocortisone, adrenaline, prochlorperazine and ranitidine, as per the hospital anaphylaxis protocol, intubation and admission to the intensive care unit. Serum tryptase levels performed during the anaphylactic event (at the end of the infusion) and 1.5 hours later showed an increase of 2 µg/L, suggestive of an anaphylactic reaction. Anaphylaxis remains largely a clinical diagnosis even in the absence of an elevated serum tryptase. The patient would benefit from further allergen testing given the severity of the reaction to alteplase. We report this patient to indicate that although rare, anaphylaxis is a recognised adverse event following alteplase. In the case of any symptoms suggestive of a minor anaphylactic reaction to alteplase, further infusion should be ceased to avoid a dose dependent major reaction.

Myrmecia pilosula (Jack Jumper) ant venom: identification of allergens and revised nomenclature.

BACKGROUND: The 'Jack Jumper Ant' (JJA; Myrmecia pilosula species complex) is the major cause of ant sting anaphylaxis in Australia. Our aims were to determine the allergenicity of previously described venom peptides in their native forms, identify additional allergens and if necessary, update nomenclature used to describe the allergens according to International Union of Immunological Societies criteria. METHODS: Various polyacrylamide gel electrophoresis methods were used to separate JJA venom. Gel resolved venom was Western-blotted and probed with individual sera taken from patients with a history of JJA sting anaphylaxis and immunoglobulin E radioallergosorbent test (IgE RAST) tracer uptakes of >1% to whole venom. RESULTS: Of 67 available sera, 54 had RAST uptakes >1%. Thirteen IgE binding bands were identified using these sera. Pilosulin 3, [Ile(5)]pilosulin 1, and pilosulin 4.1 were recognized by 42 (78%), 18 (33%) and nine (17%) of the 54 sera that were tested. Immunoglobulin E-binding proteins with estimated molecular masses of 6.6, 22.8, 25.6, 30.4, 32.1, 34.4 and 89.8 kDa were each recognized by three or more individual sera. Two of these (25.6 and 89.8 kDa) were recognized by 46% and 37% of sera, respectively. CONCLUSION: Nomenclature used to describe JJA venom allergens has been revised. Pilosulin 3 (Myr p 2) is the only major allergen, whilst [Ile(5)]pilosulin 1 (Myr p 1), and pilosulin 4.1 (Myr p 3) are minor allergens. There are an additional five IgE-binding proteins that require further characterization before they can be named as allergens. These findings provide a framework for standardizing venom extracts for diagnosis and immunotherapy.

Extrinsic factors in atopic eczema.

The debate over the role of extrinsic allergens in atopic eczema has been enlightened in recent years by some well-controlled studies and improvements in our understanding of conditions which lead to hypersensitivity. This paper reviews some of these findings, which have preventative and therapeutic implications. No attempt is made here to review other aspects of this multifactorial disease, nor to enter into detailed discussion of dietary or allergen avoidance regimens, which have been covered in several recent reviews. Such regimens are not without risk, and require expert supervision.

The source of IgM and IgG in the dog intestine.

The source of IgM and IgG2a,b in the dog intestine was investigated, using labelled dog immunoglobulins and chronic Thiry-Vella loops of dog small intestine. Clearancess of IgM and IgG2a,b from serum into intestinal secretions were similar, reflecting transfer of a greater mass of IgG2a,b than of IgM. Only 20% of the intestinal IgM derived from serum, irrespective of the marker used. About one third of the total intestinal IgG, of all sub-classes and accrued from all sources, was serum-derived IgG2a,b. This indicates that serum is a major contributor to dog intestinal IgG2a,b.

Dog immunoglobulins. II. The antibacterial properties of dog IgA, IgM and IgG antibodies to Vibrio cholerae.

Secretory IgA antibodies to Vibrio cholerae were purified from the parotid saliva and mammary secretions of locally and orally immunized dogs using gel filtration, ion-exchange chromatography and anti-immunoglobulin immuno-absorbents. IgM and IgG antibodies were isolated from serum by gel filtration and ion-exchange chromatography. IgA antibodies proved to have minimal, if any, activity in direct killing of bacteria in the presence of complement or in the promotion of phagocytosis. The minimal activity which IgA had in these assays could be accounted for by extremely small quantities of IgM antibody. The same IgA antibodies, mixed with the challenge innoculum of Vibrio cholerae and fed to infant mice, protected these mice as efficiently as IgG or IgM antibodies.

Dog immunoglobulins. I. immunochemical characterization of dog serum, parotid saliva, colostrum, milk and small bowel fluid.

The levels of immunoglobulins A, M and G were measured in dog serum, colostrum, milk, parotid saliva and small bowel fluid using the single radial immunodiffusion method. All the external secretions except early colostrum, by contrast with serum, were found to be rich in IgA with small quantities of IgM and IgG. Exocrine immunoglobulins were partially characterized by gel filtration.

Specific IgM and IgG antibodies in IgA deficiency.

Evidence of an abnormality of IgM- and IgG-specific antibody responses was sought in subjects with selective IgA deficiency. Twenty-four patients having a serum IgA level less than 0 . 37 g/l were detected by local-population screening. Total IgM and IgG levels were measured as well as specific antibody to the lipopolysaccharides of six 0 serotypes of E. coli which are frequently isolated from human faeces. Serum IgM-class E. coli antibodies were significantly lower in IgA-deficient patients than in age- and sex-matched controls. The respective IgG-class antibody was generally elevated although more variation existed in this class. There was no correlation of specific antibody in either class with the degree of IgA deficiency. Possible explanations for these patterns of antibody response are discussed. It is concluded that some subjects with 'selective IgA deficiency' may be deficient in specific IgM antibody responses to certain antigens.

Development of monoclonal mouse antibodies specific for allergenic components in ryegrass (Lolium perenne) pollen.

The development of monoclonal mouse antibodies against ryegrass (Lolium perenne) pollen allergens is described. Hybridoma colonies secreting antibodies specific for allergenic components were detected using an enzyme-linked immunosorbent assay. Positive colonies were cloned and expanded. The pollen components with which the monoclonal antibodies interact were identified and characterised following sodium dodecyl sulphate polyacrylamide gel electrophoresis and electrophoretic transfer to nitrocellulose. In this paper six monoclonal mouse antibodies are described. Three antibodies interact with a single molecule of between 30,000 and 35,000 daltons. One antibody interacts with a component of 16,000 daltons whereas the remaining two antibodies react with more than one component, one reacting with two components at 28,000 and 30,000, and the other with five components having molecular weights between 18,000 and 71,000 daltons.

Urticaria and angio-oedema.

Urticaria and angio-oedema are a symptom complex covering a wide range of clinical disorders. Specific types are now well described, and it appears that many cases of idiopathic chronic urticaria which make up the vast majority of patients referred for assessment are due to intolerance to natural salicylates, preservatives and colouring agents. There is, therefore, an urgent need for legislation to enforce the clear identification of these chemicals in processed food and drugs.

In vitro degradation of mouse, rabbit and dog antibodies to Vibrio cholerae by succus entericus.

Purified antibodies to Vibrio cholerae from mouse, rabbit and dog were digested in vitro by homologous intestinal secretions. When assessed with regard to their complement-dependent vibriocidal activity, IgG antibodies were generally more susceptible to degradation than IgM antibodies, High levels of tryptic inhibitors were required to inhibit this digestion. Rabbit IgG was unusual in being quite resistant to digestion. Gel filtration studies demonstrated that secretory IgA, isolated from mouse intestinal secretions, was resistant to proteolysis. Similar studies on dog IgG and mouse IgM demonstrated production of F(ab') 2-like fragments. Digestss of these antibodies, while devoid of Fc-mediated vibriocidal activity, retained significant protective activity for baby mice.

The effect of lysozyme on the complement-dependent bactericidal action of different antibody classes.

Preparations of rabbit, dog and sheep IgA, IgA and IgM were examined for their antibacterial effects using a complement-dependent bactericidal assay. IgM and IgG were efficient bactericidal antibodies in the presence of complement; IgA, however, contained negligible activity. Except for sheep IgG no enhancement of bactericidal activity was observed in the presence of added lysozyme.