Victor Matheu

Dual effects of vitamin d-induced alteration of TH1/TH2 cytokine expression: Enhancing IgE production and decreasing airway eosinophilia in murine allergic airway disease

BACKGROUND Vitamin D, a common food additive, has been shown to prevent the induction of experimental autoimmune diseases in mice. A possible immune deviation from T(H)1 to T(H)2 responses has been postulated. Although there is no doubt about the beneficial effects of vitamin D, its role in allergy has not been investigated. OBJECTIVE To define the role of vitamin D in modulating the development of a T(H)2-mediated disease, we used a murine model of pulmonary eosinophilic inflammation. METHODS Five-week-old mice were primed on day 0 with ovalbumin intraperitoneally. Then they were nasally challenged with ovalbumin on days 7, 8, 9, and 10, and on day 11, samples were studied. Some mice received subcutaneous injections of vitamin D every second day as follows: days -3, -1, 1, 3, 5, 7, and 9. The control groups received PBS on the same days. RESULTS Early treatment with vitamin D augmented allergen-induced T-cell proliferation along with T(H)2 cytokine (IL-4 and IL-13) and IgE production. Surprisingly, the local inflammatory response in bronchoalveolar lavage fluid and lung tissue was significantly ameliorated with impaired recruitment of eosinophils and inferior levels of IL-5. These findings were attributed to late treatment with vitamin D after establishment of an early immune response. CONCLUSION We suggest that excess supplementation of vitamin D could influence the development of a sustained T(H)2 response, leading to an increasing prevalence of allergy, whereas vitamin D might hold promising beneficial effects in airway eosinophilia.

Lupine-induced anaphylaxis

BACKGROUND Legumes are one of the most common foods causing allergic reactions in children and adults. Cross-reacting antibodies are frequently demonstrated in this family but the real clinical cross-reactivity is uncommon. OBJECTIVE To report a case of lupine-induced anaphylaxis and to elucidate in vivo and in vitro cross-reactivity with some legumes. METHODS Skin prick test (SPT) with some legumes were performed. Cap-IgE, ELISA-IgE, and immunoblotting were carried out. Open oral challenges with some legumes were performed. Cross-reactivity was studied by ELISA and immunoblotting inhibition. RESULTS The results demonstrated type-I hypersensitivity reactions with lupine and some other legumes. Cap-IgE with peanut was positive but the SPT and ELISA-IgE were negative and the patient tolerated a peanut challenge. ELISA inhibition revealed a partial inhibition (62%) using lupine as the solid phase. Partial inhibition was demonstrated by immunoblotting inhibition. Open oral challenge with peanut and green bean were negative but positive with pea. CONCLUSION We present a lupine sensitized patient with positive SPT and in vitro cross-reactivity with other legumes. Clinical cross-reactivity progressively developed over a 5-year period. Discrepancies were found between the clinical aspect and in vitro study of peanut allergy. Factors determining the wide variability in cross-reactivity among individuals are still obscure.

Characterization of allergens secreted by Anisakis simplex parasite: clinical relevance in comparison with somatic allergens

Background Diagnostic methods for the study of allergic reactions to Anisakis simplex (A.s.) based on whole‐body extracts of the larva are clearly insufficient.

Insulin allergy and resistance successfully treated by desensitisation with Aspart insulin

A 25-year-old, with type I Diabetes Mellitus with a previous diagnosis of Protamine Allergy but not to human Insulin, started to notice anaphylactic reactions inmmediatly after bolus with Insulin. Skin prick and intradermal test were positive to all insulins. Skin tests to other potential allergens resulted negative. Examination after bolus of Human Insulin revealed urticaria. Daily insulin requirement were around 2-2,4 U/Kg/day. Slow desensitisation with Aspart insulin, the insulin with lowest size of skin test, was performed using subcutaneous insulin pump. Six months after the end of desensitisation his daily insulin requirement decreased to 0.8 U/Kg/day and oral corticosteroids are being reduced with no symptoms.

Anisakis simplex-sensitized patients: should fish be excluded from their diet?

BACKGROUND Anisakis simplex (A.s.) allergy is an emerging disease. The third-stage larvae of this nematode are a source of hidden allergens in fish. There are no clear guidelines concerning dietary restrictions for patients with serum-specific IgE to this parasite. OBJECTIVE To follow up the clinical data and immunological parameters of patients sensitized to A.s. during 6 to 23 months. METHODS The clinical symptoms and serologic status of 17 patients with specific IgE and positive skin prick test results to A.s. were studied prospectively. Six of these had anaphylaxis (ANA) attributed to A.s. and 11 patients experienced concomitant chronic urticaria (CU). All patients were advised not to eat fish for 6 months. RESULTS Four patients from the ANA group excluded fish, and ANA did not recur. Two other patients with ANA refused to exclude fish; one remained free of symptoms and the other experienced several urticarial episodes. During this 6-month period total IgE levels decreased in all six ANA patients; specific IgE for A.s. decreased in four patients and increased in two. Two patients from the CU group did not exclude fish, and symptoms persisted in these two patients. Clinical improvement was observed in 78% of the patients with CU who excluded fish. Total and specific IgE levels decreased in all the patients with CU. CONCLUSIONS Because ANA symptoms are very severe, patients should always be advised to exclude fish until specific food allergens are identified. However, in patients with CU and specific IgE to A.s., only the clinical response to fish ingestion will determine the need for strict fish avoidance.

T cell activity in successful treatment of chronic urticaria with omalizumab

Omalizumab, a humanized monoclonal anti-IgE antibody has the potential to alter allergen processing. Recently, it has been postulated the assessment of PHA-stimulated adenosine triphosphate (ATP) activity as maker of CD4+ T cells activity in peripheral blood cells. We present the case report of a 35-year-old woman with a history of chronic idiopathic urticaria and angioedema of 8 years of development with poor response to treatment. The patient was partially controlled with cyclosporine at doses of 100 mg/12 h. However, she was still developing hives daily. Finally treatment with omalizumab was started at dose of 300 mg every 2 weeks. The patient experienced a decrease in urticarial lesions 2 days after starting therapy. We also evaluated the effects of omalizumab therapy on the activity of peripheral blood CD4+ T cells from the patient, in order to determine the potential modification of anti-IgE therapy on the process of antigen presentation-recognition. Activity of CD4+ cells by ATP release was clearly increased demonstrating an enlarged CD4 activity. Omalizumab may be useful in the treatment of severe chronic urticaria. ATP activity of peripheral blood CD4+ T cells might be a non-subjective method to assess Omalizumab activity.

Importance of repeat testing in the diagnosis of penicillin allergy

SIR, In the May 2005 issue of this Journal Lammintausta and Kortekangas-Savolainen presented an interesting article about the usefulness of skin tests in determining drug hypersensitivity. We have found the results to be very helpful as there are only few reported works about the prevalence of positive skin tests in the context of allergic reactions. However, we have some points of contention. Although both patch tests (PTs) and intradermal tests (IDTs) are used for the diagnosis of nonimmediate reactions to aminopenicillins, and both tests appear to be valuable, delayed-reading IDTs appear to be somewhat more sensitive than PTs, but also less specific. In the report by Lammintausta and Kortekangas-Savolainen, beta-lactam antibiotics were the drugs more often suspected and tested. However, IDTs with major and minor determinants were carried out only in 31 of 342 patients with suspected penicillin allergy and none of them elicited a positive reaction. The European Network for Drug Allergy (ENDA) recommends testing in most patients in whom penicillin allergy is suspected. In fact, most diagnoses of penicillin allergy have recently been reported to be obtained by means of the IDT. Between January 2002 and June 2005 we evaluated 604 patients with suspected betalactam allergy. In all of them, after written informed consent, skin prick tests and IDTs were performed with benzylpenicilloyl polylysine (PPL), minor determinants mixture (MDM; including benzylpenicillin, benzylpenicilloic acid and sodium benzylpenicilloate), penicillin G and the suspect drug if it was other than penicillin. PPL and MDM were purchased from two different companies (Allergopen ; Allergopharma, Reinbeck, Germany and Diater SA, Madrid, Spain). If the skin tests were negative, controlled drug challenge was performed under strict supervision. After 15 days the skin tests and drug challenge were repeated, as recommended by ENDA. After completing the study, 66 patients were diagnosed with beta-lactam allergy, 60 by skin testing and 10 of those in the repeat tests. From 1108 challenges with beta-lactams in 554 patients, there were only six positives following a previously negative skin test. In the report by Lammintausta and Kortekangas-Savolainen, repeat testing was not carried out. ENDA describes that the natural history of allergy to penicillin is such that patients may lose sensitivity or become negative in skin testing. Because of that, repeat testing has been recommended in patients with a positive history and negative skin and in vitro tests, even in those showing a good tolerance after drug provocation testing. ENDA recommends that repeat testing should follow the same protocol and be performed between 2 weeks and 1 month after the first tests. Our results showed that 16% of subjects (10 of 60) who showed tolerance to beta-lactams in the first challenge were diagnosed as sensitive after repeat testing. In one patient with an unequivocal history of allergy to penicillin a third evaluation was necessary to produce a positive skin test. Although penicillin allergy has been vastly overdiagnosed, and too many people are incorrectly labelled as allergic to penicillin, misdiagnosis is also a risk to consider, as a considerable percentage of patients was able to lose sensitivity or was negative in the first evaluation. Repeat testing, which could be considered as a booster, and the determination of specific IgE levels, will help to obtain an accurate diagnosis of beta-lactam allergy, although the majority of the penicillin-allergic donors failed to produce penicillin-specific IgE in vitro, when their lymphocytes were cultured in the presence of allergen.

Oral mite anaphylaxis by Thyreophagus entomophagus in a child: a case report.

Sensitization to Thyreophagus entomophagus, a storage mite, is uncommon and might produce occupational respiratory disorders in farmers. We present the first case of a child suffering anaphylaxis produced by ingestion of contaminated flour with Thyreophagus entomophagus.

Impact on allergic immune response after treatment with vitamin A

BackgroundVitamin A may have some influence on the immune system, but the role in allergy modulation is still unclear.ObjectiveTo clarify whether high levels of retinoic acid (RA) affects allergic response in vivo, we used a murine experimental model of airway allergic disease.MethodsOvalbumin (OVA)-immunization/OVA-challenge (OVA/OVA) and house dust mite (HDM)-immunization/HDM-challenge (HDM/HDM) experimental murine models of allergic airway disease, using C57Bl.10/Q groups of mice (n = 10) treated subcutaneously with different concentrations of all-trans RA (0, 50, 500 and 2,500 ug) every 2-days were used to assess the allergic immune response.ResultsLevels of total and specific-IgE in sera were increased in all groups of RA treated OVA/OVA and HDM/HDM mice. Percentage and total amount of recruited eosinophil in airways by bronchoalveolar lavage fluid (BALF) were significantly enhanced in groups treated with 50, 500 and 2,500 ug of RA compared to non-treated mice. However, the group of mice treated with 2,500 ug had less eosinophil recruitment than the other two groups (50 and 500 ug). In parallel, levels of IL-5 and total IgE in BALF were also significantly diminished in the group treated with 2,500 ug compared to the other 2 groups (50 and 500 ug). Finally, total lung resistance was decreased in group treated with 2,500 ug compared to non-treated mice.ConclusionOur results suggest that retinoic acid directly enhances allergic response in vivo, but in higher doses may produce of immune suppression.

Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-β knock-out mice

BackgroundCpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-β in the immunomodulatory effects of CpG-ODN is not known.ObjectiveHere, we aimed to elucidate the role of IFN-β in the anti-allergic effect of CpG motifs.MethodsWe assessed the immune response in OVA-primed/OVA-challenged IFN-β knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment with synthetic CpG motifs.ResultsVaccination with CpG-ODN reduced the number of cells in airways of OVA-sensitized WT but not IFN-β-/- mice. Although airway eosinophilia was reduced in both treated groups, they were significantly higher in IFN-β-/- mice. Other inflammatory cells, such as lymphocytes and macrophages were enhanced in airways by CpG treatment in IFN-β-/- mice. The ratio of IFN-γ/IL-4 cytokines in airways was significantly skewed to a Th1 response in WT compared to IFN-β-/- group. In contrast, IL-4 and IgE were reduced with no differences between groups. Ag-specific T-cell proliferation, Th1-cytokines such as IFN-γ, IL-2 and also IL-12 were significantly lower in IFN-β-/- mice. Surprisingly, we discovered that intranasal treatment of mice with CpG-ODN results in mild synovitis particularly in IFN-β-/- mice.ConclusionOur results indicate that induction of Th1 response by therapy with CpG-ODN is only slightly and partially dependent on IFN-β, while IFN-β is not an absolute requirement for suppression of airway eosinophilia and IgE. Furthermore, our finding of mild synovitis is a warning for possible negative effects of CpG-ODN vaccination.