Immuno-evasive tactics by schistosomes identify an effective allergy preventative.

Many chronic inflammatory diseases can be improved by helminth infection, but the mechanisms are poorly understood. Allergy and helminthiasis are both associated with Th2-like immune responses; thus, defining how infection with parasites leads to reduced allergy has been particularly challenging. We sought to better understand this conundrum by evaluating host-parasite interactions involved in Th2 immunity in human schistosomiasis. Immune cells were cultured with schistosomes and the effect on CD23, an IgE receptor associated with resistance in schistosomiasis, was evaluated. Cells treated with schistosomes demonstrated reduced surface CD23 levels with a parallel accumulation of soluble (s) CD23 suggesting this IgE receptor is proteolytically cleaved by the parasite. Consistent with this hypothesis, a schistosome-generated (SG)-sCD23 fragment of 15 kDa was identified. SG-sCD23 inhibited IgE from binding to CD23 and FcεRI, but lacked the ability to bind CD21. These results suggested that schistosomes target IgE-mediated immunity in immuno-evasive tactics. Based on its characteristics, we predicted that SG-sCD23 would function as an efficacious allergy preventative. Treatment of human FcεRI-transgenic mice with recombinant (r) SG-sCD23 reduced the ability of human IgE to induce an acute allergic response in vivo. In addition, an optimized form of rSG-sCD23 with an introduced point mutation at Asp258 (D258E)to stabilize IgE binding had increased efficacy compared to native rSG-sCD23. Schistosome infection may thus inhibit allergic-like protective immune responses by increasing soluble IgE decoy receptors. Allergy treatments based on this naturally occurring phenomenon may be highly effective and have fewer side effects with long-term use.

FcRγ promotes contact hypersensitivity to oxazolone without affecting the contact sensitisation process in B6 mice.

The process of sensitisation by specific contact allergens is indispensable for the induction of allergic contact dermatitis. Oxazolone is a well-characterised contact allergen. Previous studies suggested that immune cells bearing the FcRγ subunit are essential for oxazolone-induced contact hypersensitivity, but the biological functions of the FcRγ subunit in the process of sensitisation to oxazolone remain unknown. In this study, we show that FcRγ deficiency decreases ear-swelling responses to oxazolone in mice. However, we found that oxazolone-sensitised FcRγ(-/-) mice and oxazolone-sensitised wild-type (WT) mice have comparable numbers of CD11c(+) MHCII(hi) dendritic cells (DCs) in their draining lymph nodes (LNs). In addition, oxazolone-sensitised LN cells from both FcRγ(-/-) and WT mice showed considerable production of interferon-gamma (IFNγ), interleukin-4 (IL-4) and IL-17A upon oxazolone-keyhole limpet haemocyanin loading. Consistent with these data, oxazolone-sensitised FcRγ(-/-) and FcRγ(+/+) LN cells conferred contact hypersensitivity to WT naïve mice challenged with the hapten. Our findings clearly indicate that, in an experimental mouse model, the FcRγ subunit positively regulates contact hypersensitivity to oxazolone without affecting the contact sensitisation process.

Clinical value of morphine, pholcodine and poppy seed IgE assays in drug-abusers and allergic people

Background: The diagnosis of anaphylactic reactions due to opiates during anaesthesia can be difficult, since in most cases various drugs may have been administered. Detection of specific IgE to poppy seed might be a marker for sensitisation to opiates in allergic people and heroin-abusers. This study assessed the clinical value of morphine, pholcodine and poppy seed skin-prick and IgE determination in people suffering hypersensitivity reactions during anaesthesia or analgesia and drug-abusers with allergic symptoms. Methods: We selected heroin abusers and patients who suffered severe reactions during anaesthesia and analgesia from a database of 23,873 patients. The diagnostic yield (sensitivity, specificity and predictive value) of prick and IgE tests in determining opiate allergy was analysed. Results: Overall, 149 patients and 200 controls, mean age 32.9±14.7 years, were included. All patients with positive prick to opiates showed positive prick and IgE to poppy seeds, but not to morphine or pholcodine IgE. Among drug-abusers, 13/42 patients (31%) presented opium hypersensitivity confirmed by challenge tests. Among non-drug abusers, sensitisation to opiates was higher in people allergic to tobacco (25%), P<0.001. Prick tests and IgE against poppy seed had a good sensitivity (95.6% and 82.6%, respectively) and specificity (98.5% and 100%, respectively) in the diagnosis of opiate allergy. Conclusions: Opiates may be significant allergens. Drug-abusers and people sensitised to tobacco are at risk. Both the prick and specific IgE tests efficiently detected sensitisation to opiates. The highest levels were related to more-severe clinical profiles(AU)

Serum total IgE level during pregnancy and postpartum

Background: Studies on serum IgE levels during pregnancy are limited. Objective: To investigate the course of serum total IgE levels during pregnancy and postpartum. Methods: 159 pregnant subjects provided 218 serum samples during various stages of pregnancy and the postpartum period. Serum total IgE geometric means were compared at various trimesters and postpartum. In addition, the postpartum IgE data were analysed according to the method of delivery. Analysis was also done according to history of allergy. Results: The geometric mean serum total IgE was 20.5 IU/ml in the first trimester, 20.8 IU/ml in the second and 22.2 IU/ml in the third. Postpartum serum IgE level showed a lower mean, 14.9 IU/ml during the early postpartum period (less than 30 days) compared to 30.3 IU/ml during the late postpartum period (30 days-25 weeks). However this was not statistically significant. Serum IgE in the postpartum period also did not differ according to method of delivery. A history of allergy was positive in 98 samples, negative in 61 and unclear in 59. Using analysis of variance, none of these three groups showed significant change in serum total IgE level during pregnancy or postpartum. Conclusion: In this cross-sectional study, serum total IgE levels showed no statistically significant changes during pregnancy or postpartum. This finding would be of greater weight if reproduced in a larger number of subjects with multiple serial samples at fixed regular time intervals during pregnancy and postpartum (AU)

Systemic administration of an Fcgamma-Fc(epsilon)-fusion protein in house dust mite sensitive nonhuman primates.

Crosslinking Fc(epsilon)RI and FcgammaRIIB receptors inhibits mast cell and basophil activation, decreasing mediator release. In this study, a fusion protein incorporating human Fcgamma and Fc(epsilon) domains, hGE2, was shown to inhibit degranulation of human mast cells and basophils, and to exhibit efficacy in a nonhuman primate model of allergic asthma. hGE2 increased the provocative concentration of dust mite aeroallergen that induced an early phase asthmatic response. The treatment effect lasted up to 4 weeks and was associated with reduction in the number of circulating basophils and decreased expression of Fc(epsilon)RI on repopulating basophils. Repeat hGE2 dosing induced production of serum antibodies against human Fcgamma and Fc(epsilon) domains and acute anaphylaxis-like reactions. Immune serum induced histamine release from human IgE or hGE2-treated cord blood-derived mast cells and basophils in vitro. These results indicate that repeat administration with hGE2 induced an antibody response to the human molecule that resulted in activation rather than inhibition of allergic responses.

Relación entre inmunoglobulina E sérica total y VEF1 como indicador de severidad del asma bronquial en pacientes adultos / Relation between total serum immunoglobulin E and VEF1 as indicator of severity of the bronchial asthma in adult patients

La prevalencia del asma bronquial se ha incrementado progresivamente en las últimas décadas, particularmente en los países industrializados. También es mayor la presencia de formas graves de la enfermedad y por lo tanto resulta necesario reconocer condiciones que puedan relacionarse con la gravedad de la misma. El objetivo primario del presente trabajo fue investigar si los niveles de IgE sérica total (IgEST) guardan relación con la severidad del asma bronquial determinada por la disminución del volumen espiratorio forzado en el primenr segundo (VEF1). Como objetivos secundarios se evaluaron si otros marcadores de atopia, tales como las respuestas cutáneas a alergenos ambientales, u otros datos clínicos (edad, género, síntomas rinosinuales crónicos, alergia alimentaria y antecedentes heredofamiliares de asma o alergia) podrían resultar también predictores de la gravedad de la patología, valorada por espirometría. Se incluyeron 63 pacientes asmáticos adultos, sin tratamientos óptimos para su patología bronquial y sin otras condiciones capaces de modificar la función ventilatoria mensurable por espirometría. Se excluyeron los enfermos con afecciones capaces de elevar la IgE, distintas de la atopia.