IgE Titers Research Articles

Spontaneous food allergy in Was-/- mice occurs independent of FcεRI-mediated mast cell activation.

Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was-/- mice recapitulates the pathology of a conventional disease model and/or human food allergy. Comparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was-/- mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high-affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was-/- Fcer1a-/- mice. Polysensitization to food was detected in both WAS and food-allergic patients which was recapitulated in the Was-/- model. Oral administration of ovalbumin (OVA) in Was-/- mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was-/- mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was-/- mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells (MCs) and basophils. Was-/- mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food.

Apheresis in food allergies.

The prevalence of IgE-mediated food allergy and anaphylaxis has risen rapidly in developed countries, and countries with rapid industrialization may follow. Therapies include elimination diets, Oral ImmunoTherapy, and the administration of biologics, but high serum IgE levels may preclude their use. Consequently, decreasing IgE becomes a rational approach and could be obtained by immunoapheresis. The aim of this review is to evaluate the rationale and advantages of immunoapheresis. The majority of the available adsorbers remove aspecifically all classes of immunoglobulins. Recently, IgE-specific adsorbers have been approved. Data on immunoapheresis for the treatment of allergic diseases with pathologically elevated IgE levels are emerging. In atopic dermatitis, this therapy alone seems to be beneficial. IgE-selective apheresis appears to be sufficient to reduce the risk of anaphylaxis in multiple food allergy (MFA) and, when IgE titers are high, to open the way to treatment with Omalizumab. Prospective studies, with well designed protocols, are needed to assess the efficacy, tolerability, and cost-effectiveness of immunoapheresis in the field of food allergy.

Inducing maternal inflammation promotes leptin production in offspring but does not improve allergic symptoms in a mouse model of allergic rhinitis

AimsThe intrauterine environment is considered to affect immunological development in fetus, leading to an increased risk of developing allergy. In particular, maternal lipopolysaccharides (LPS) administration might regulate the development of allergic disease in offspring. Several studies have shown that being obese relates to a higher prevalence of allergic diseases compared to normal weight. The present study explored the effects of inducing maternal inflammation with LPS before pregnancy on body weight, physical composition including body fat, adipokine production, and pathology of allergic rhinitis in offspring.Main methodsFemale mice received a single intraperitoneal injection of LPS (2 μg/g BW). After 5 days of LPS administration, female mice were mated with males, and experimental allergic rhinitis was induced in female offspring. Immunization and nasal challenge with ovalbumin (OVA) were performed at 7 and 8 weeks of age. Allergic rhinitis-like symptoms, OVA-specific IgE and adipokines in sera, body weight, fat pad weight, and cytokine production by splenocytes in these 9-week-old offspring.Key findingsMaternal LPS administration results in a significant increase in body weight, visceral fat accumulation, and serum leptin concentration, and the dominance of Th1 in Th balance. Nevertheless, there was no statistical difference in OVA-specific IgE titer and allergic-like symptoms between the groups.SignificanceIn conclusion, maternal LPS promoted leptin production and altered Th balance in mice offspring, but not improved allergic symptoms in a mouse model of allergic rhinitis. It might suggest that inflammation during pregnancy plays a role in the adipose tissue function which could diversely influence allergic inflammation in offspring.

Fusion of Fc domain to Factor IX (FIX) modulates the Th2 biased response to FIX and triggers Th1 immunity in hemophilia B treated mice.

Abstract Fusion of the IgG1 constant region domain (Fc) to therapeutic proteins increases the plasma half-life of drugs via binding to the neonatal Fc receptor (FcRn). However, potential interactions with Fc gamma-receptors (FcγR) expressed by immune cells may effect the immunogenicity of these drugs. The coagulation factors VIII (FVIII) and IX (FIX) for the treatment of hemophilia A & B (HA & HB) are the only drugs available with and without Fc fusion and offer an opportunity to experimentally study the effect of Fc fusion. Anti FVIII & FIX antibodies (ADAs) and rare cases of anaphylaxis in HB patients, are serious safety concerns. Using a mouse model for HB, we compared the immune responses to infusions of recombinant human FIX (hFIX) and hFIX fused to mouse IgG2a-Fc (hFIX-mFc). The mFc allowed species-specific Fc-FcγR interactions and prevented immune response to the foreign hFc. Treatment with hFIX-mFc caused earlier onset of anti-FIX IgG and elicited higher FIX-neutralizing antibody levels. Treatment with hFIX triggered Th2 biased immunity i.e., elevated plasma IgE titers, and Th2 cytokine profile of FIX-specific CD4 T cells and a few anaphylactic events. The fusion of Fc altered the response to a Th1 type with increased plasma IFN-γ levels, and IFN-γ secretion by effector CD4 T cells. hFIX-mFc binds to soluble FcγRs and FcγRs on natural killer cells (which also secrete IFNγ) and antigen presenting cells (dendritic cells, and macrophages source of IL-12). We show that Fc fusion enhances the presentation of hFIX to CD4 T cells. We propose that high plasma availability and targeting of APC provide plausible mechanisms by which the Fc fusion may modulate the CD4 T cell response to hFIX towards a Th1 like response, thus avoiding allergic responses.

Aerobic Exercise Decreases Lung Inflammation by IgE Decrement in an OVA Mice Model.

Aerobic exercise (AE) reduces lung function decline and risk of exacerbations in asthmatic patients. However, the inflammatory lung response involved in exercise during the sensitization remains unclear. Therefore, we evaluated the effects of exercise for 2 weeks in an experimental model of sensitization and single ovalbumin-challenge. Mice were divided into 4 groups: mice non-sensitized and not submitted to exercise (Sedentary, n=10); mice non-sensitized and submitted to exercise (Exercise, n=10); mice sensitized and exposed to ovalbumin (OVA, n=10); and mice sensitized, submitted to exercise and exposed to OVA (OVA+Exercise, n=10). 24 h after the OVA/saline exposure, we counted inflammatory cells from bronchoalveolar fluid (BALF), lung levels of total IgE, IL-4, IL-5, IL-10 and IL-1ra, measurements of OVA-specific IgG1 and IgE, and VEGF and NOS-2 expression via western blotting. AE reduced cell counts from BALF in the OVA group (p<0.05), total IgE, IL-4 and IL-5 lung levels and OVA-specific IgE and IgG1 titers (p<0.05). There was an increase of NOS-2 expression, IL-10 and IL-1ra lung levels in the OVA groups (p<0.05). Our results showed that AE attenuated the acute lung inflammation, suggesting immunomodulatory properties on the sensitization process in the early phases of antigen presentation in asthma.

Oralair ® real-world treatment pattern from a French cohort study

Introduction Allergic rhinitis (AR) has been reported to affect between 20% and 40% of the world population. Oralair ® obtained indication for the treatment of grass pollen allergic rhinitis with or without conjunctivitis in adults, adolescents and children (above the age of 5) with clinically relevant symptoms, confirmed by a positive skin test and/or a positive titre of specific grass pollen IgE. The French Health Technology Assessment agency requested to set up a post-authorisation cohort study to describe Oralair ® real-world treatment pattern and patients characteristics. Methods Patients with an initiation of Oralair ® before pollen season in 2015, were included in a cohort study and followed by allergy specialists to the end of the pollen season. Results 90 allergy specialists included 280 adults and 203 children, with a mean age of 33.8 years and 11.8 years at inclusion, 49.6% men and 63.5% boys, age of onset of AR = 15.2 (±10.2) and 4.0 (±2.9) years, 87.1% and 83.7% with conjunctivitis, 41.4% and 34.3% had asthma, 87.9% and 85.2% of AR classified as persistent during the year before, 98.6% and 92.6% as moderate-severe (ARIA classification). A skin test was performed for all patients. Oralair ® was started 3–5 months before pollen season for 85.1% and continued during pollen season for most patients, with a mean duration of 2.5 months. Treatment was discontinued early ( Conclusion This study shows that the conditions of Oralair ® prescriptions by allergy specialists followed the indication recommendations well, and were associated with an improvement of AR severity observed for more than 3 patients out of 5, with a resolution of main previous AR symptoms for about half of the patients.

Modulating immunogenicity of factor IX by fusion to an immunoglobulin Fc domain: a study using a hemophilia B mouse model

Background Fc fusion is a platform technology used to increase the circulating half-life of protein and peptide therapeutics. However, there are potential immunological consequences with this approach, such as changes in the molecule's immunogenicity as well as possible interactions with a repertoire of Fc receptors (FcR) that can modulate immune responses. Objectives/Methods Using a mouse hemophilia B (HB) model, we compared the immune responses to infusions of recombinant human factor IX (hFIX) and hFIX fused to mouse IgG2a-Fc (hFIX-mFc). The mFc was employed to allow species-specific Fc-FcγR interactions. Results Although treatment with hFIX-mFc altered the early development of anti-FIX IgG, no significant differences in anti-FIX antibody titers were observed at the end of the treatment regimen (5 weeks) or upon anamnestic response (5 months). However, treatment with hFIX-mFc elicited higher FIX-neutralizing antibody levels and resulted in reduced IgE titers compared with the hFIX-treated group. Additionally, differences in plasma cytokine levels and in vitro CD4+ T-cell responses suggest that whereas hFIX treatment triggered a Th2-biased immune response, hFIX-mFc treatment induced Th1-biased CD4+ T cells. We also show that hFIX-mFc bound to soluble FcγRs and engaged with FcγRs on different cell types, which may impact antigen presentation. Conclusions These studies provide a model system to study how Fc-fusion proteins may affect immune mechanisms. We used this model to demonstrate a plausible mechanism by which Fc fusion may modulate the IgE response to hFIX. This model may be appropriate for investigating the rare but severe IgE-mediated anaphylaxis reaction to hFIX infusions in HB patients.

Lifelong memory responses perpetuate humoral TH2 immunity and anaphylaxis in food allergy

A number of food allergies (eg, fish, shellfish, and nuts) are lifelong, without any disease-transforming therapies, and unclear in their underlying immunology. Clinical manifestations of food allergy are largely mediated by IgE. Although persistent IgE titers have been attributed conventionally to long-lived IgE+ plasma cells (PCs), this has not been directly and comprehensively tested. We sought to evaluate mechanisms underlying persistent IgE and allergic responses to food allergens. We used a model of peanut allergy and anaphylaxis, various knockout mice, adoptive transfer experiments, and invitro assays to identify mechanisms underlying persistent IgE humoral immunity over almost the entire lifespan of the mouse (18-20months). Contrary to conventional paradigms, our data show that clinically relevant lifelong IgE titers are not sustained by long-lived IgE+ PCs. Instead, lifelong reactivity is conferred by allergen-specific long-lived memory B cells that replenish the IgE+ PC compartment. B-cell reactivation requires allergen re-exposure and IL-4 production by CD4 T cells. We define the half-lives of antigen-specific germinal centers (23.3days), IgE+ and IgG1+ PCs (60 and 234.4 days, respectively), and clinically relevant cell-bound IgE (67.3days). These findings can explain lifelong food allergies observed in human subjects as the consequence of allergen exposures that recurrently activate memory B cells and identify these as a therapeutic target with disease-transforming potential.

Randomised controlled trial of a baked egg intervention in young children allergic to raw egg but not baked egg

Background Consumption of baked egg by raw egg allergic children is associated with immune changes suggesting development of tolerance. However, causation has not been tested using a double blind randomized controlled trial (RCT). We aimed to compare clinical and immunological outcomes after baked egg (BE) consumption in young BE tolerant egg allergic children.Methods In a double blind RCT, BE tolerant egg allergic children consumed 10 g BE (1.3 g protein) 2 to 3 times per week for 6 months (n = 21 intervention group) or similar egg free baked goods (n = 22 control group) while maintaining an otherwise egg free diet. The final assessment was a raw egg oral food challenge (OFC) 1 month after ceasing the intervention product. Egg specific IgE and IgG4 were assessed at baseline and 7 months.Results After the intervention there was no difference in raw egg tolerance between groups, (23.5% (4/17) intervention group and 33.3% (6/18) control group). This was independent of age and amount of BE consumed (aOR 0.50 CI 0.11–2.40 p = 0.39). Both groups demonstrated decreased egg specific serum IgE titres and decreased whole egg specific IgE/IgG4 ratios.Discussion We conducted this trial because inclusion of baked egg protein in the diet of egg allergic children appears to move children towards a more tolerant immune profile. Strengths of our study include design of the blinded intervention, the consistent dosing protocol and the regular monitoring of symptoms and intake. However, the study was limited by small sample size resulting in insufficient power to show statistically significant results.Conclusion Our study suggests that short term, regular consumption of BE by BE tolerant 1 to 5 year old children with IgE mediated raw egg allergy may not induce, accelerate or slow development of tolerance to raw egg in this selected population. Trials with larger sample sizes are required to further test this hypothesis.Trial Registration The trial was registered on 7th February 2012 with the Australian New Zealand Clinical Trials Registry (ACTRN 12612000173897).

Adjuvant effect of Asparagus racemosus Willd. derived saponins in antibody production, allergic response and pro-inflammatory cytokine modulation.

The study manifests the immunoadjuvant potential of saponin rich fraction from Asparagus racemosus in terms of cellular and humoral immune response that can be exploited against microbial infections. Asparagus racemosus (AR) has been attributed as an adaptogen and rasayana in traditional medication systems for enhancing the host defence mechanism. Spectrophotometric and HPTLC analysis ensured the presence of saponins. The saponin rich fractions were tested for immunoadjuvant property in ovalbumin immunised mice for the humoral response, quantified in terms of prolonged antibody production upto a duration of 56days. Proinflammatory cytokines (IL-6 and TNF) were estimated for the cellular immune response in LPS stimulated primary murine macrophages. The safety evaluation in terms of cytotoxicity and allergic response has also been evaluated through in-vitro (MTT) and in-vivo (IgE) respectively. ARS significantly inhibited the pro-inflammatory cytokines, in LPS stimulated murine macrophages with no intrinsic cytotoxicity. The significant increase in IgG production infers the utility of ARS for prolonged humoral response. Further, the antigen specific response of IL-12 at early stage and IgE titres also suggests the generation of cellular immune response and low allergic reaction respectively, as compared to conventional adjuvants. IL-6 and TNF fluctuations in LPS stimulated and non-stimulated macrophages along with IgG and IL-12 also confirmed the Th1/Th2 modulating effect of ARS. The study indicates potential effect of ARS as an adjuvant for the stimulation of cellular immune response in addition to generating a sustained adaptive response without any adverse effects paving way for further validation with pathogenic organisms.

Expression of α-1,6-fucosyltransferase (FUT8) in rice grain and immunogenicity evaluation of plant-specific glycans

Rice seed is a cost-effective bioreactor for the large-scale production of pharmaceuticals. However, convincing evidence of the immunogenicity of plant-specific glycans is still limited although plant-specific glycans are considered potential allergic antigens. In the present study, we found that the α-1,3-fucose content of the glycoprotein produced from rice seed was much lower than that in leaf, and conversely, a higher β-1,2-xylose content was detected in seed than that in leaf. We detected the α-1,6-fucose content in the glutelin and recombinant human α1-antitrypsin (OsrAAT). The further results in a line containing AAT and FUT8 genes indicated that the α-1,6-fucose content of modified glycosylated recombinant α1-antitrypsin (mgOsrAAT) was 38.4%, while glutelin was only 6.8%. Interestingly, the α-1,3-fucose content of mgOsrAAT was significantly reduced by 59.8% compared with that of OsrAAT. Furthermore, we assessed the immunogenicity of OsrAAT, mgOsrAAT and human α1-antitrypsin (hAAT) using an animal system. The PCA results indicated no significant differences in the IgG, IgM and IgE titers among OsrAAT, mgOsrAAT and hAAT. Further studies revealed that those antibodies were mainly from α-1,3-fucose, but not from β-1,2-xylose, indicating that α-1,3-fucose was the major immunogenic resource. Our results demonstrated that α-1,3-fucose contents in seed proteins was much less than that of leaf, and could not be a plant-specific glycan because it also exists in human proteins.

Immunodominance in allergic T-cell reactivity to Japanese cedar in different geographic cohorts

BackgroundJapanese cedar (JC) pollen is a common trigger for allergic rhinitis in Japan. Pollen proteins targeted by IgE, including Cry j 1 and Cry j 2, and isoflavone reductase (IFR) have been identified. ObjectiveTo compare antigen-specific IgE titers and T-cell responses to JC pollen–derived extract and peptides in cohorts with high and low pollen exposure. MethodsPeripheral blood mononuclear cells from JC pollen allergic or nonallergic patients who have lived in Japan for at least 1 year and JC pollen allergic patients who have never been to Japan were tested for T-cell responses against JC pollen extract and peptide pools derived from Cry j 1, Cry j 2, or IFR. T-cell reactivity was assessed by interleukin 5 and interferon γ production by ELISPOT. ResultsJC pollen–specific T-cell reactivity and IgE titers were significantly higher in the allergic compared with the nonallergic Japanese cohort, which was also associated with different patterns of polysensitization. Interestingly, a significant overlap was observed in the hierarchy of the T-cell epitopes in the allergic Japanese cohort compared with the allergic non-Japanese cohort. In all 3 cohorts, T-cell reactivity was dominantly directed against peptides from the major allergens Cry j 1 and 2, with few T-cell responses detected against IFR. ConclusionOur studies identify common denominators of T-cell reactivity in patient populations with different sensitization patterns, suggesting that generally applicable immunotherapeutic approaches might be developed irrespective of exposure modality.

Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency.

Deficiency of secreted IgM (sIgM-/-) accelerates atherosclerosis in Ldlr-/-mice. Several atheroprotective effects of increased levels of IgM antibodies have been suggested, including preventing inflammation induced by oxidized low-density lipoprotein and promoting apoptotic cell clearance. However, the mechanisms by which the lack of sIgM promotes lesion formation remain unknown. To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice. We here show that both sIgM-/- and Ldlr-/-sIgM-/- mice develop increased plasma IgE titers because of impaired generation of B cells expressing the low-affinity IgE receptor CD23, which mediates the clearance of IgE antibodies. We further report that Ldlr-/-sIgM-/- mice exhibit increased numbers of activated mast cells and neutrophils in the perivascular area of atherosclerotic plaques. Treatment with an anti-IgE-neutralizing antibody fully reversed vascular inflammation and accelerated atherosclerotic lesion formation in cholesterol-fed Ldlr-/-sIgM-/- mice. Thus, our data identify a previously unsuspected mechanism by which sIgM deficiency aggravates atherosclerosis.

Post-Fecal Microbiota Transplantation (FMT) Constipation and Abdominal Distention Due to Methane-Predominant Bacterial Overgrowth Contracted from the Donor

FMT is becoming increasingly used in patients with severe, recurrent and/or relapsing Clostridium difficile infections (CDI). Despite durable benefits associated complications are poorly defined. Up to 10% of patients develop bloating and constipation after FMT (Lee CH 2014); however, causality is not established as most patients undergoing FMT are ill and suffer from significant gastrointestinal (GI) symptoms. Excessive methane production (>10 ppm) is present in up to 25% of the general population and can lead to constipation and bloating. (Chang 2015) Here we report a 21 year-old female with history of recurrent sinusitis due to IgA deficiency requiring multiple courses of antibiotics and no prior GI-related complaints. She contracted CDI in Jan 2014, which persisted despite treatment with vancomycin and metronidazole. In July 2014, she underwent FMT via colonoscopy from her stepbrother. Despite eradication of CDI, she developed significant post-prandial bloating, distention, fatigue and constipation without rectal bleeding or constitutional symptoms. Her physical exam was without focal abnormalities. Laboratory evaluation showed normal IgG and IgM levels, but undetectable IgA and IgE titres. ANA was slightly elevated at 1:80, however CRP, anti-CCP, anti-tTG, C3, C4, LFTs, lipase CBC, and electrolytes were normal. Anti-vinculin and anti-CdtB antibodies were negative, as were stool for C. difficile, elastase, calprotectin and O&P. EGD and ileocolonoscopy were normal with normal gastric and duodenal biopsies. Capsule endoscopy and CT of the abdomen were normal. Antidepressants, low FODMAPs diet, peppermint, over-the-counter laxatives, linaclotide, lubiprostone and prucalopride proved to be minimally effective. Breath testing performed in Oct 2014 showed normal hydrogen levels, but significantly elevated methane peaking at 51 ppm (Figure 1). On further testing, FMT donor was also found to be an excessive methane producer, with a methane level of 35 ppm. The patient was treated with 14 days of rifaximin 550 mg TID and neomycin 500 mg BID leading to eradication of excessive methane production to 0 ppm and resolution of her GI symptoms. CDI has not recurred as of June 2016. This is the first report of methane-predominant bacterial overgrowth contracted from the FMT donor as a potential cause of post-FMT IBS-like symptoms such as bloating and constipation. Screening of FMT donors for excessive methane production may prevent such complications.Figure 1

Relationship between specific IgE to egg components and natural history of egg allergy in Danish children.

The majority of egg-allergic children develop tolerance over time. However, it may take numerous of consecutive egg challenges to get there as no good indices to predict tolerance exist. To investigate whether serial measurements of specific IgE to egg white, ovomucoid, ovalbumin, conalbumin, lysozyme, and egg yolk could improve the specificity of the diagnostic workup and aid in the decision when to rechallenge egg-allergic children. The outcome of oral food challenges with hen's egg and corresponding specific IgE levels were evaluated in children referred to The Allergy Center within an 8-year period. The egg-allergic children were rechallenged and had specific IgE levels measured once a year. During a median follow-up of 26 months, 287 challenges and corresponding 287 serum analyses were performed in 130 children. Of the 130 children, 99 were egg allergic and 82 of these were rechallenged. Based on the initial diagnostic challenges only, area under the curve (AUC) estimates of the ability of specific IgE titers to distinguish between egg sensitization and egg allergy were only modest (maximum 0.83) and provided no clinical meaningful decision points. Specific IgE levels at baseline did not differ between tolerant and persistent allergic children. However longitudinally, acquisition of tolerance was associated with a decrease in IgE to egg white and to ovomucoid. In all cases of an increase in IgE to ovomucoid, the rechallenge was positive. The decision when to rechallenge egg-allergic children should encounter the course of specific IgE.

Determination of specific IgE in pericardial and cerebrospinal fluids in forensic casework

The aim of this study was to characterize total and specific IgE distribution in postmortem serum as well as pericardial and cerebrospinal fluid samples and evaluate the diagnostic usefulness of total and specific IgE determination in pericardial and cerebrospinal fluids in the forensic setting. Three groups were investigated (non-allergic deaths in non-atopic individuals, fatal allergic anaphylaxis deaths and non-allergic deaths in individuals without medical records). In the first group (non-allergic deaths in non-atopic individuals), total IgE concentrations in postmortem serum from femoral blood, pericardial and cerebrospinal fluids were lower than 40, 32 and 11kU/l, respectively. No specific IgE were identified in any of the sampled fluids. In the second group (fatal allergic anaphylaxis deaths), total IgE concentrations in postmortem serum from femoral blood ranged from 139kU/l to 818kU/l, in pericardial fluid from 89kU/l to 622kU/l and in cerebrospinal fluid from 4kU/l to 11kU/l. A positive Phadiatop® test and specific IgE antibodies >0.35kU/l were found exclusively in postmortem serum from femoral blood and pericardial fluid. In the third group (non-allergic deaths in individuals without medical records, possibly including atopic individuals), total IgE concentrations ranged from 42kU/l to 516kU/l in postmortem serum from femoral blood, from 34kU/l to 417kU/l in pericardial fluid and from 3kU/l to 12kU/l in cerebrospinal fluid. A positive Phadiatop® test and specific IgE antibodies >0.35kU/l were found exclusively in postmortem serum from femoral blood and pericardial fluid. These results seem to suggest that total and specific IgE may be measured in postmortem serum from femoral blood and pericardial fluid to estimate total and specific IgE titers at the time of death. Conversely, cerebrospinal fluid total and specific IgE measurement in suspected IgE mediated fatal anaphylaxis cases is of no value for diagnostic purposes.

Changes over Time in IgE Sensitization to Allergens of the Fish Parasite Anisakis spp.

BackgroundSensitization to Anisakis spp. can produce allergic reactions after eating raw or undercooked parasitized fish. Specific IgE is detected long after the onset of symptoms, but the changes in specific IgE levels over a long follow-up period are unknown; furthermore, the influence of Anisakis spp. allergen exposure through consumption of fishery products is also unknown.ObjectiveTo analyse the changes in IgE sensitization to Anisakis spp. allergens over several years of follow-up and the influence of the consumption of fishery products in IgE sensitization.MethodsTotal IgE, Anisakis spp.-specific IgE, anti-Ani s 1 and anti-Ani s 4 IgE were repeatedly measured over a median follow-up duration of 49 months in 17 sensitized patients.ResultsAnisakis spp.-specific IgE was detected in 16/17 patients throughout the follow-up period. The comparison between baseline and last visit measurements showed significant decreases in both total IgE and specific IgE. The specific IgE values had an exponential or polynomial decay trend in 13/17 patients. In 4/17 patients, an increase in specific IgE level with the introduction of fish to the diet was observed. Three patients reported symptoms after eating aquaculture or previously frozen fish, and in two of those patients, symptom presentation was coincident with an increase in specific IgE level.ConclusionsIgE sensitization to Anisakis spp. allergens lasts for many years since specific IgE was detectable in some patients after more than 8 years from the allergic episode. Specific IgE monitoring showed that specific IgE titres increase in some allergic patients and that allergen contamination of fishery products can account for the observed increase in Anisakis spp.-specific IgE level.Clinical RelevanceFollowing sensitization to Anisakis spp. allergens, the absence of additional exposure to those allergens does not result in the loss of IgE sensitization. Exposure to Anisakis spp. allergens in fishery products can increase the specific IgE level in some sensitized patients.

Mucosal expression of DEC-205 targeted allergen alleviates an asthmatic phenotype in mice

Considering the rising incidence of allergic asthma, the symptomatic treatments that are currently applied in most cases are less than ideal. Specific immunotherapy is currently the only treatment that is able to change the course of the disease, but suffers from a long treatment duration. A gene based immunization that elicits the targeting of allergens towards dendritic cells in a steady-state environment might have the potential to amend these difficulties. Here we used a replication deficient adenovirus to induce the mucosal expression of OVA coupled to a single-chain antibody against DEC-205. A single intranasal vaccination was sufficient to mitigate an OVA-dependent asthmatic phenotype in a murine model. Invasive airway measurements demonstrated improved lung function after Ad-Dec-OVA treatment, which was in line with a marked reduction of goblet cell hyperplasia and lung eosinophilia. Furthermore OVA-specific IgE titers and production of type 2 cytokines were significantly reduced. Together, the here presented data demonstrate the feasibility of mucosal expression of DEC-targeted allergens as a treatment of allergic asthma.

Trichinella spiralis infection and transplacental passage in human pregnancy

Infection by Trichinella spp. during pregnancy still arises many questions. Worldwide an important number of trichinellosis outbreaks have occurred over time where pregnant women were or might have been involved.Parasitological and immunoserological parameters, clinical background and transplacental passage of Trichinella spiralis of six pregnant women, from different outbreaks, were studied.Serum samples were collected from patients and their children: at pregnancy, at delivery, newborn and/or infant (≥1 year-old). Total immunoglobulins (Igs) and isotypes against excretion-secretion products from muscle larvae (ESP-ML) and newborn larvae (NBL) of T. spiralis were detected by immunoserological techniques. Sera helminthocytotoxic activity against NBL was evaluated by antibodies dependent cell cytotoxicity assay.Patients presented similar clinical symptoms. Mother's sera showed differences in the presence and titres of Igs, IgE, IgG1 and IgG4 against NBL surface. All of them showed helminthocytotoxic activity against NBL, four in progesterone dependent manner and the other two by antibodies. Igs anti ESP-ML were present in mother's sera, with differences in the isotypes detected. Anti-ESP-ML IgE, IgA and/or IgM in newborn sera were observed. Three out of four infants showed specific Igs; one even at 8 years-old.The distinct immune response between mothers at pregnancy evidenced by sera helminthocytotoxic activity and immunoserological parameters may be associated with a different parasite burden exposition. Specific Igs observed in newborns would be a suggestion of transplacental passage of this Igs and/or their production by the fetus. Specific Igs found in infants sera suggests that newborn larvae transplacental passage is possible.

Transiently increased IgE responses in infants and pre-schoolers receiving only acellular Diphtheria–Pertussis–Tetanus (DTaP) vaccines compared to those initially receiving at least one dose of cellular vaccine (DTwP) – Immunological curiosity or canary in the mine?

BackgroundSeveral previous studies have highlighted the strong Th2-polarising and IgE-promoting activity of the DTaP vaccine, but there is no evidence that this has pathological consequences and accordingly there is no current interest amongst vaccine developers in reformulating DTaP to attenuate these properties. In light of an apparent resurgence in pertussis in many countries, and emerging evidence from other areas of paediatric immunology of IgE-mediated interference with host defence mechanisms, this issue requires more detailed clarification. MethodsWe have re-evaluated the impact of DTaP-only versus mixed DTwP/DTaP vaccination on Th2-dependent “bystander” IgE responses in three cohorts of children under different priming conditions, encompassing both vaccine-targeted and unrelated antigens including food allergens. ResultsWe confirm the generalised IgE-trophic activity of the DTaP vaccine in pre-schoolers and demonstrate similar (albeit transient) effects in infants. We additionally demonstrate that use of an alternative mixed infant priming schedule encompassing an initial dose of DTwP significantly attenuates this property. InterpretationCentral to our interpretation of these findings are studies demonstrating: (i) mixed DTwP/DTaP priming improves resistance to pertussis disease and attenuates the IgE-stimulatory component of long term vaccine-specific memory; (ii) IgE-mediated mechanisms can interfere with innate antiviral immunity and accordingly exacerbate airway symptoms in infected children. These observations, taken together with the data presented here, suggest a plausible mechanistic link between baseline pertussis-specific IgE titres in DTaP vaccinees and susceptibility to pertussis disease, which merits testing. Retrospective IgE analyses on sera collected from children at the time of presentation with pertussis could resolve this issue.