IgE-associated Allergic Disease Research Articles

Enterosorbents in complex therapy of food allergies: a focus on digestive disorders and systemic toxicity in children.

The review analyzes mechanisms and concomitant factors in developing IgE-associated allergic diseases provoked by food allergens and discusses clinical symptoms and current approaches for the treatment of food allergies. The expediency of using enterosorbents in complex therapy of food allergies and skin and respiratory manifestations associated with gastroenterological disorders is substantiated. The review summarizes the experience of using enterosorbents in post-Soviet countries to detoxify the human body. In this regard, special attention is paid to the enterosorbent White Coal (Carbowhite) based on silicon dioxide produced by the Ukrainian company OmniFarma.

Temporal and Long-term Gut Microbiota Variation in Allergic Disease: A Prospective Study from Infancy to School Age

How the early-life gut microbiota changes over time has been implicated in the development of immunoglobulin E– (IgE) mediated allergic diseases, but there is lack of data from longitudinal studies. In this study, researchers compared gut microbiota from infancy to school age in relation to the onset of allergic disease while also examining the relationship of gut microbiota to T-cell activation at age 8 years.Ninety-three children were included from a randomized, placebo-controlled trial in which researchers investigated the effects of probiotics for primary prevention of allergic disease. That original trial group consisted of 179 infants without previous allergic manifestations who were randomly assigned to a daily intake of infant cereals with or without the probiotic Lactobacillus paracasei.Parents reported signs and symptoms of atopic disease and medications by using diary cards. Stool samples were collected at 4, 6, and 13 months and at age 8 years. Clinical follow-up was conducted at age 8 to 9 years. Clinical diagnoses for eczema and asthma were established primarily by history, those with allergic rhinitis also had evidence of IgE sensitization, and food allergy was diagnosed by history of reaction within 1 hour of food ingestion and/or documented IgE sensitization. The gut microbiota was profiled taxonomically using 16S ribosomal RNA gene sequencing. Mononuclear cells from peripheral blood drawn at age 8 years were polyclonally activated, and levels of interleukin-10 and FOXP3 messenger RNA were determined.At age 8 years, 21 children had allergic disease, with 20 being sensitized to airborne allergens and 13 to foods. Seventy-two children were nonallergic and nonsensitized. The longitudinal design allowed for the study of compositional changes in gut microbiota from infancy through school age in relation to development of IgE-associated allergic disease. Allergic children had temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus from infancy through age 8 years. The gut microbiota in 8-year-olds who were allergic was enriched in Bifidobacterium and depleted in Lactobacillus, Enterococcus, and Lachnospira; and in this same group, Faecalibacterium correlated with interleukin-10 messenger RNA levels. FOXP3 trended similarly and was not statistically significant. There were no significant differences in whether the children had received the Lactobacillus probiotic in infancy.There are both temporal and long-term variations in specific gut bacterial genera in children developing allergic disease. Dietary interventions aimed at expanding gut immunomodulatory taxa could be studied for preventing allergic disease.The authors describe how certain gut organisms, especially commensal Clostridia, colonize specific regions of the intestinal mucosa and may play key roles as immunomodulators. Given the compelling hereditary nature of atopic disease irrespective of diet, why are certain bacterial taxa more or less represented at this seemingly important intestinal mucosal location? Might not gut bacterial taxa be the result of the atopic milieu, therefore making efforts to ameliorate atopic disease by the planned ingestion of certain bacteria moot?

Temporal and long-term gut microbiota variation in allergic disease: A prospective study from infancy to school age.

Compositional changes in the early-life gut microbiota have been implicated in IgE-associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE-associated allergic diseases. At 8years of age, we also examined the relationship between gut microbiota and T-cell regulation, estimated as responses to polyclonal T-cell activation. Stool samples were collected from 93 children at 4, 6, 13months, and 8years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL-10 and FOXP3 mRNA copies were determined using real-time quantitative reverse transcriptase-PCR. At 8years of age, 21 children were diagnosed with IgE-associated allergic disease and 90% displayed allergic comorbidity. Seventy-two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8-year-olds was enriched in Bifidobacterium and depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8-year-olds, Faecalibacterium correlated with IL-10 mRNA levels (rs =0.49, Padj =0.02) with the same trend for FOXP3 (rs =0.39, Padj =0.08). We identified both temporal and long-term variation in the differential abundance of specific bacterial genera in children developing IgE-associated allergic disease. Improved dietary interventions aiming at expanding immune-modulatory taxa could be studied for prevention of allergic disease.

Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen.

Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development of allergen delivery systems enabling more efficient delivery and hence lower allergen load might reduce the adverse events. In the present study, we have investigated neutral and cationic liposomes as delivery systems of ovalbumin (OVA), as a model allergen, in an OVA-induced allergic airway inflammation model. We investigated the liposome carriers’ ability to improve tolerance induction of antigens compared to the corresponding dose of free OVA. Mice were treated sublingually over 2 weeks with free or liposome encapsulated OVA followed by intraperitoneal injections and intranasal challenge. Mice sublingually treated with OVA-liposomes showed a significant reduction of airway eosinophilia and splenocyte proliferation in comparison to free OVA. A similar nonsignificant pattern was seen for OVA-specific IgE antibodies. In addition, reduced levels of interferon-γ and interleukin-5 were observed in spleen cell culture supernatants from OVA-liposome-treated mice compared to the sham-treated group. In conclusion, in vivo efficacy data showed that prophylactic SLIT with OVA-liposomes is significantly more effective in preventing allergic inflammation than the corresponding dose of free OVA.

IgE-associated allergic disorders: recent advances in etiology, diagnosis, and treatment.

IgE-associated allergic diseases belong to the most common inflammatory conditions. Their clinical manifestation ranges from mild symptoms to life-threatening episodes. Often patients experience a reduction in physical and psychologic well-being and suffer from a decreased quality of life due to disease activity. The continuously rising number of people that are affected by an allergic condition indicates an urgent need for better diagnostics and more efficient treatment options. Recent progress in the understanding of pathophysiologic mechanisms underlying IgE-associated allergic disorders has led to the identification of novel therapeutic targets and the development of drug candidates that are currently under evaluation. In this review, we highlight studies and clinical trials, which have helped to gain further insight in the etiology of IgE-associated allergic conditions as well as advances in the development of diagnostic tools and therapeutic approaches recently published in Allergy (European Journal of Allergy and Clinical Immunology).

Prenatal Fish Oil Supplementation and Allergy: 6-Year Follow-up of a Randomized Controlled Trial.

Evidence from randomized controlled trials in early infancy suggest that prenatal supplementation with Ω-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease characterized by an immunoglobulin E (IgE) response. We aimed to determine whether protective effects were evident in the 6-year-old offspring of women supplemented with n-3 rich fish oil during pregnancy. Six-year follow-up of children (n = 706) with a family history of allergic disease from the Docosahexaenoic Acid to Optimize Mother Infant Outcome (DOMInO) trial. Women were randomly allocated to receive n-3 LCPUFA-rich fish oil capsules (800 mg/d docosahexaenoic acid DHA and 100mg/d eicosapentaenoic acid) or vegetable oil capsules (without n-3 LCPUFA). Allergic disease symptoms including eczema, wheeze, rhinitis, and rhino-conjunctivitis, were assessed using the International Study of Asthma and Allergies in Childhood questionnaire and sensitization to allergens was measured by skin prick test. There was no difference in the percentage of children with any IgE-associated allergic disease between the n-3 LCPUFA and control groups (116/367 [31.5%] vs 106/336 [31.5%]; adjusted relative risk, 1.04; 95% confidence interval, 0.82-1.33; P = .73). There was a reduction in the percentage of children sensitized to house dust mite Dermatophagoides farinae (49/367 [13.4%] vs 68/336 [20.3%]; adjusted relative risk, 0.67, 95% confidence interval, 0.44-1.00; P = .0495). Prenatal n-3 LCPUFA supplementation did not reduce IgE-associated allergic disease at 6 years of age. Secondary outcomes were suggestive of a protective effect of the intervention on the incidence of D. farinae sensitization.

Altered MicroRNA Expression Profiles in Activated Mast Cells Following IgE-FcεRI Cross-Linking with Antigen

Background/Aims: MicroRNAs (miRNAs) are critical regulators of immune responses and immunologic disorders. However, little is known about miRNA expression and function during mast cell differentiation, proliferation and activation. This study aimed to determine the miRNA expression profiles in mast cells stimulated by immunoglobulin E (IgE) and antigen and to analyze the potential functions of specific miRNAs. Methods: Bone marrow-derived mast cells (BMMCs) generated from differentiated mouse bone marrow cells were untreated (Unstimu) or stimulated with IgE-antigen complexes for 1 h or 6 h (Stimu). The miRNA profiles were evaluated by miRNA microarray. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. Results: Seven significantly up-regulated and 10 down-regulated miRNAs were identified in the 1 h Stimu group relative to the Unstimu group (fold change>2; P<0.05). Of 8 miRNAs randomly selected from the 17 identified, the expression levels of 6 were confirmed by quantitative real-time PCR (qRT-PCR). The potential target genes of several candidate miRNAs were enriched in FcεRI signaling, response to stimulus and cellular exocytosis. Conclusion: The expression of many miRNAs changes following IgE-FcεRI cross-linking in activated mast cells, and these miRNAs probably play key regulatory roles in core signaling pathways and biological behaviors. Evaluating the functions of these characteristic miRNAs will further our understanding of IgE-associated allergic disease pathogenesis and the development of therapeutic strategies.

Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies

Diets high in n-3 long chain polyunsaturated fatty acids (LCPUFA) may modulate the development of IgE-mediated allergic disease and have been proposed as a possible allergy prevention strategy. The aim of this study was to determine whether n-3 LCPUFA supplementation of pregnant women reduces IgE-mediated allergic disease in their children. Follow-up of children (n = 706) at hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome randomized controlled trial. The intervention group (n = 368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n = 338) received matched vegetable oil capsules without n-3 LCPUFA. The diagnosis of allergic disease was made during medical assessments at 1 and 3 years of age. No differences were seen in the overall percentage of children with IgE-mediated allergic disease in the first 3 years of life between the n-3 LCPUFA and control groups (64/368 (17.3%) vs 76/338 (22.6%); adjusted relative risk 0.78; 95% CI 0.58-1.06; P = 0.11). Eczema was the most common allergic disease; 13.8% of children in the n-3 LCPUFA group had eczema with sensitization compared with 19.0% in the control group (adjusted relative risk 0.75; 95% CI 0.53-1.05; P = 0.10). Overall, n-3 LCPUFA supplementation during pregnancy did not significantly reduce IgE-associated allergic disease in the first 3 years of life. Further studies should examine whether the nonsignificant reductions in IgE-associated allergies are of clinical and public health significance.

No effect of probiotics on respiratory allergies: a seven‐year follow‐up of a randomized controlled trial in infancy

Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy. This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age. To evaluate whether perinatal and infant supplementation with L. reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects. A randomized, placebo-controlled trial with oral supplementation with L. reuteri ATCC 55730 (1 × 10(8) CFU) during the last month of gestation and through the first year of life comprising 232 families with allergic disease, of whom 184 completed a 7-yr follow-up. The primary outcomes at 7 yr of age were allergic disease and skin prick test reactivity (ClinicalTrials.gov ID NCT01285830). The prevalence of asthma (15% in the probiotic vs. 16% in placebo group), allergic rhinoconjunctivitis (27% vs. 20%), eczema (21% vs. 19%) and skin prick test reactivity (29% vs. 26%) was similar in the probiotic and placebo group. Growth indices and gastrointestinal symptoms were similar in the two groups. No severe adverse events were reported. The effect of L. reuteri on sensitization and IgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age. Thus, the effect of L. reuteri on the immune system seems to be transient. Administration of L. reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects.

Probiotics in primary prevention of allergic disease - follow-up at 8-9 years of age

Long-term effects of probiotics in primary prevention of allergic disease need further evaluation. We previously reported a reduced cumulative incidence of infant eczema by feeding Lactobacillus paracasei ssp paracasei F19 (LF19) during weaning. Therefore, we assessed effects of LF19 on the prevalence of allergic disease at school age. In a double-blind placebo-controlled trial infants were randomized to daily intake of cereals with (n = 89) or without LF19 10(8) CFU (n = 90) from 4-13 months of age. At age 8-9, we evaluated the prevalence of allergic disease (eczema, allergic rhinitis, asthma, and food allergy) by clinical examination and validated questionnaires. IgE sensitization was assessed by skin prick test (inhalant allergens) and specific IgE levels (food allergens). Lung function was evaluated by a spirometry reversibility test. Fractional exhaled nitric oxide (FENO ) was measured. Of 171 children that completed the intervention, 121 were assessed at age 8-9. In the probiotic group, 15/59 (25%) were diagnosed with any allergic disease vs 22/62 (35%) in the placebo group [OR (95% CI) 0.62 (0.28-1.36)]. Corresponding numbers for IgE-associated allergic disease were 9/53 (17%) vs 12/59 (20%) [0.80 (0.31-2.09)]. Median (25th-75th percentile) FENO was 9 (8-12) in the probiotic vs 8 (7-12) ppb in the placebo group (P > 0.05). There was no effect of LF19 on lung function measures (P > 0.05). There was no long-term effect of LF19 on any diagnosed allergic disease, airway inflammation or IgE sensitization. This suggests delayed eczema onset but to fully examine long-term benefits a larger study population had been needed.

Fishing for allergy prevention

Fishing for allergy prevention

MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine

The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.

Probiotics in the treatment and prevention of allergies in children.

Several studies on the pathogenesis of allergy both in man and experimental animals continue to show the importance of commensal bacteria in the gastrointestinal tract in stimulating and directing the immune system. The interest in modulating commensal bacteria flora with pre- and probiotics to prevent and treat food allergy has multiplied in recent years. We recently studied 230 infants with atopic dermatitis and suspected cow’s milk allergy. The infants were randomly allocated to groups which received Lactobacillus GG (LGG), a mixture of four probiotic strains (MIX) or placebo for 4 weeks. We inferred that probiotics induce systemically detectable low-grade inflammation, which may explain the clinical effects and the secretion pattern of cytokines induced by PBMC. To study the ability of probiotics to prevent allergy in children, we recruited 1223 pregnant women carrying fetuses at increased risk of allergy for a double-blind placebo-controlled trial. Mothers used a mixture of four probiotic bacteria or a placebo from the 36th week of gestation. Their infants received the same probiotics plus prebiotic galacto-oligosaccharides for 6 months. At the 2-year follow-up, a total of 925 infants participated. The cumulative incidence of allergic disease did not differ significantly between the synbiotic and the placebo group. However, synbiotics significantly reduced eczema. The preventive effect of synbiotics was more pronounced against IgE-associated diseases. At the 5 year follow-up, 891(88%) of the 1018 intention-to-treat infants attended. In the probiotic and placebo groups, frequencies of allergic symptoms and IgE-associated allergic disease and sensitization were similar, and the frequencies of eczema did not differ between the groups. Atopic eczema, allergic rhinitis and asthma appeared equal frequency in the groups. However, less IgE-associated allergic disease occurred in the cesarean-delivered infants given probiotics. In cesarean-delivered childen, we noticed a delayed rise in bifidobacteria recovery in placebo-treated children which was corrected by pro- and prebiotic supplementation. Indications from studies of feces and blood at the age 6 months suggest that probiotics may enhance both inflammation and immune defence of the gut. The probiotic treatment further stimulated maturation of the immune system since the infants given probiotics showed increased resistance to respiratory infections and improved vaccine antibody responses.

High intestinal IgA associates with reduced risk of IgE‐associated allergic diseases

Development of oral tolerance and its stimulation by probiotics are still incomprehensible. Microbial stimulation of the gut may induce a subtle inflammation and induce secretion of mucosal IgA, which participates in antigen elimination. In a cohort of allergy-prone infants receiving probiotics and prebiotics or placebo we studied intestinal IgA and inflammation in the development of eczema, food allergy, asthma, and rhinitis (allergic diseases). We performed a nested unmatched case-control study of 237 infants participating in a randomized double-blind placebo-controlled allergy-prevention trial using a combination of four probiotic strains pre-natally and during 6 months form birth. We measured faecal IgA, alpha1-antitrypsin (alpha1-AT), tumour necrosis factor-alpha (TNF-alpha), and calprotectin at the age of 3 and 6 months. By age 2 yr, 124 infants had developed allergic disease or IgE-sensitization (cases) and 113 had not (controls). In infants with high faecal IgA concentration at the age of 6 months, the risk of having any allergic disease before the age of 2 yr tended to reduce [odds ratio (OR: 0.52)] and the risk for any IgE-associated (atopic) disease reduced significantly (OR: 0.49). High faecal calprotectin at the age of 6 months associated also with lower risk for IgE-associated diseases up to age 2 yr (OR: 0.49). All faecal inflammation markers (alpha1-AT, TNF-alpha, and calprotectin) correlated positively with faecal IgA (p < 0.001). Probiotics tended to augment faecal IgA (p = 0.085) and significantly increased faecal alpha1-AT (p = 0.001). High intestinal IgA in early life associates with minimal intestinal inflammation and indicates reduced risk for IgE-associated allergic diseases.

Th1 and Th2 Chemokines, Vaccine-Induced Immunity, and Allergic Disease in Infants After Maternal ω-3 Fatty Acid Supplementation During Pregnancy and Lactation

We investigated whether the previously reported preventive effect of maternal ω-3 fatty acid supplementation on IgE-associated allergic disease in infancy may be mediated by facilitating a balanced circulating Th2/Th1 chemokine profile in the infant. Vaccine-induced immune responses at 2 y of age were also evaluated. Pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo from the 25th gestational week through 3.5 mo of breastfeeding. Infant plasma was analyzed for chemokines (cord blood, 3, 12, 24 mo) and anti-tetanus and anti-diphtheria IgG (24 mo). High Th2-associated CC-chemokine ligand 17 (CCL17) levels were associated with infant allergic disease (p < 0.05). In infants without, but not with, maternal history of allergy, the ω-3 supplementation was related to lower CCL17/CXC-chemokine ligand 11 (CXCL11) (Th2/Th1) ratios (p < 0.05). Furthermore, in nonallergic, but not in allergic infants, ω-3 supplementation was linked with higher Th1-associated CXCL11 levels (p < 0.05), as well as increased IgG titers to diphtheria (p = 0.01) and tetanus (p = 0.05) toxins. Thus, the prospect of balancing the infant immune system toward a less Th2-dominated response, by maternal ω-3 fatty acid supplementation, seems to be influenced by allergic status.

Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort

Less microbial exposure in early childhood is associated with more allergic disease later. Allergic children have a different fecal microflora, with less lactobacilli and bifidobacteria. Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation. We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies. In a double-blinded, placebo-controlled study we randomized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture (2 lactobacilli, bifidobacteria, and propionibacteria) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months. Infants also received a prebiotic galacto-oligosaccharide or placebo. At 5 years, we evaluated the cumulative incidence of allergic diseases (eczema, food allergy, allergic rhinitis, and asthma) and IgE sensitization. Of the 1018 intent-to-treat infants, 891 (88%) attended the 5-year visit. Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar: 52.6% versus 54.9% and 29.5% versus 26.6%, respectively, and 41.3% in both. No significant difference appeared in frequencies of eczema (39.3% vs 43.3%), atopic eczema (24.0% vs 25.1%), allergic rhinitis (20.7% vs 19.1%), or asthma (13.0% vs 14.1%) between groups. However, less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics (24.3% vs 40.5%; odds ratio, 0.47; 95% CI, 0.23% to 0.96%; P = .035). No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children. It conferred protection only to cesarean-delivered children.

An in vivo model of allergic inflammation: pulmonary human cell infiltrate in allergen‐challenged allergic Hu‐SCID mice

CB.17 severe combined immunodeficient (SCID) mice were used to establish a model of allergic pulmonary inflammation. SCID mice were intraperitoneally reconstituted with 10(7) peripheral blood mononuclear cells (PBMC) from patients sensitive to Dermatophagoides pteronyssinus (Dpt) and 2 weeks later were exposed to Dpt aerosols. After Dpt nebulization, SCID mice engrafted with PBMC from Dpt-sensitive patients developed a specific human IgE response as well as an intense pulmonary infiltrate of human cells. In contrast, SCID mice reconstituted with PBMC from patients allergic to grass pollen or from non-allergic donors failed to produce IgE or to exhibit a similar inflammatory response. The level of the IgE production was dependent on the IgE level of the allergic donor. In the lungs of the same allergic SCID mice, 2 months after Dpt inhalation, the cell infiltrate contained CD45+, CD45RO+, CD20+ and HLA-DR+ human cells. They were located in perivascular and peribronchial areas and disseminated in the mouse lung parenchyma. Moreover, mRNA IL-5+ cells and eosinophils were found in peribronchial infiltrates. The observations indicate that humanized allergic SCID mice may develop, after nebulization with the relevant allergen, immune reactions similar to those observed in man and suggest that SCID mice may represent a useful model to analyze the regulatory mechanisms of IgE-associated allergic diseases.