IgE Titers Research Articles

Fungal allergic sensitisation in young rural Zimbabwean children: Gut mycobiome and seroreactivity characteristics.

The prevalence of allergic diseases has increased over the last few decades, with sensitisation to fungal allergens and gut microbiome dysbiosis implicated in this trend. The fungal community in the gut (mycobiome) has yet to be characterised and related to fungal allergic sensitisation. Thus, we characterised the gut mycobiome and related it to fungal sensitisation and seroreactivity among Zimbabwean children. We further determined the effect of host age, sex, Schistosoma haematobium infection and mycobiome composition on fungal sensitisation and seroreactivity. Using shotgun metagenomic sequencing, we characterised the gut microbiome of stool samples of 116 preschool aged children (PSAC) (≤5 years old, 57(49.1%) male and 59 (50.9%) female). Sensitisation to common fungi in Zimbabwe was assessed using skin prick tests (SPTs). Allergen-specific IgM, IgA, IgG, IgE and IgG4 antibodies were quantified by ELISA. We analysed the relationship between fungal genera and SPT reactivity by ANOVA; fungal genera and IgE antibody reactivity by linear regression; variation in mycobiome abundance with host and environmental factors by PERMANOVA; SPT reactivity and host and environmental factors by logistic regression; seroreactivity and host and environmental factors by ANOVA. The mycobiome formed <1% of the sequenced gut microbiome and 228 fungal genera were identified. The most abundant genera detected were Protomyces, Taphrina, and Aspergillus. S.haematobium infection had a significant effect on fungal genera. Prevalence of SPT sensitisation to ≥1 fungal species was 96%, and individuals were frequently sensitised to Saccharomyces cerevisiae. Antibodies were detected in 100% of the population. There was no relationship between mycobiome abundance and IgE titres or IgE/IgG4 ratios for each fungal species; no significant differences between SPT reactivity and abundance of fungal species except for S. cerevisiae; and fungal seroreactivity did not significantly differ with age. There were some sex (m>f for, Epicoccum nigrum and Penicillium chrysogenum) and SPT reactivity -related differences in seroreactivity. This is the first comprehensive characterisation of gut mycobiome and fungal allergic sensitisation of rural children in Zimbabwe. Although reported allergic disease is low there is a high percentage of sensitisation. Further studies with larger populations are required to understand the role of the mycobiome in allergic diseases.

The Majority of Children Sensitized Before School-Age Develop Allergic Disease Before Adulthood: A Longitudinal Population-Based Study

Allergic sensitization increases the risk of asthma and allergic rhinitis, but the impact of age at onset of sensitization is less studied. To examine the cumulative incidence of asthma and rhinitis up to age 19 years in relation to age at onset of sensitization to airborne allergens. All children in grade 1 and 2 (median age, 8 years) in 2 municipalities in Northern Sweden were invited to undergo skin prick tests and answer a questionnaire about allergic diseases, and 88% participated. At ages 12 and 19 years, the protocol was repeated, and 1510 individuals participated in all 3 examinations. Specific IgE data were collected in a random sample at age 19 years (n= 770). Onset of sensitization was defined: 8 years or less, 8 to 12 years, 12 to 19 years, and never sensitized. Adjusted Poisson regression was used to calculate risk ratios (RRs). At 19 years, those sensitized at 8 years of age or earlier had the highest risk of asthma (RR, 4.68; 95% CI, 3.15-6.97) and rhinitis (RR, 22.3; 95% CI, 13.3-37.6), and 84% had developed either asthma or rhinitis. The combination of sensitization at age 8 years or earlier and family history of allergic diseases rendered high risks for asthma (RR, 10.6; 95% CI, 6.71-16.7) and rhinitis (RR, 36.3; 95% CI, 18.9-69.7). Individuals sensitized at age 8 years or earlier showed significantly highest level of sensitization, as judged by number of positive skin test results and titers of specific IgE. Most individuals with sensitization at age 8 years or earlier developed asthma or rhinitis before young adulthood. The high level of sensitization in those sensitized early contributes to the high incidence of allergic airway conditions.

Suitable Interpretation of Skin Prick Test and Biomedical Guidance Leads to a Better Clinical State in Atopic Individuals with High Indoor Permanence: Possible Therapeutic Implications

Indoor conditions contribute to allergen sensitization and multiple allergens reactivity, mainly for inhaled allergens. This study analyzes if Skin Prick Test (SPT) combined with efficient individual biomedical guidance about allergy development’s social, biological, and environmental aspects can yield a better clinical state with therapeutic implications for atopic individuals with high indoor permanence. We recruited atopic and non-atopic volunteers (clinically and in vitro diagnosed) with indoor permanence above 15 h per day and without previous SPT evaluation. The SPT and serum anti-allergen IgE analyses were performed individually in person, demonstrated, and discussed by the practitioners. Six months after, SPT and specific IgE titers determination were repeated, and a questionnaire to evaluate the effectiveness of the practitioner’s orientation was performed. After six months, 14% of atopic volunteers reported changes in their social habits, 30% said that they avoid the development of allergies clinical symptoms, and 68% reported a substantial improvement in their health after being informed mentored about their allergen reactivity. The control non-atopic group, as expected, reported no changes in social habits, the maintenance of total avoidance of allergic symptoms, and almost no improvement of their health. Reduced SPT and serum allergen-specific IgE titers were detected in the atopic individuals corroborating with questionnaire results. Our results indicated that SPT, followed by an individual and efficient discussion about the main biomedical aspects of allergy development, could exert a pronounced therapeutic role in allergy development by high indoor permanence individuals.

Abstracts from The International Society for Aerosols in Medicine 23rd ISAM Congress Boise, Idaho May 22–26, 2021

Abstracts from The International Society for Aerosols in Medicine 23rd ISAM Congress Boise, Idaho May 22–26, 2021

Pollen antigens and atmospheric circulation driven seasonal respiratory viral outbreak and its implication to the Covid-19 pandemic

The patterns of respiratory virus illness are expressed differently between temperate and tropical climates. Tropical outbreaks often peak in wet seasons. Temperate outbreaks typically peak during the winter. The prevailing causal hypotheses focus on sunlight, temperature and humidity variations. Yet no consistent factors have been identified to sufficiently explain seasonal virus emergence and decline at any latitude. Here we demonstrate close connections among global-scale atmospheric circulations, IgE antibody enhancement through seasonal pollen inhalation, and respiratory virus patterns at any populated latitude, with a focus on the US. Pollens emerge each Spring, and the renewed IgE titers in the population are argued to terminate each winter peak of respiratory illness. Globally circulated airborne viruses are postulated to subsequently deposit across the Southern US during lower zonal geostrophic winds each late Summer. This seasonally refreshed viral load is postulated to trigger a new influenza outbreak, once the existing IgE antibodies diminish to a critical value each Fall. Our study offers a new and consistent explanation for the seasonal diminishment of respiratory viral illnesses in temperate climates, the subdued seasonal signature in the tropics, the annually circulated virus phenotypes, and the northerly migration of influenza across the US every year. Our integrated geospatial and IgE hypothesis provides a new perspective for prediction, mitigation and prevention of the outbreak and spread of seasonal respiratory viruses including Covid-19 pandemic.

Camel milk: a possible alternative for children with cow's milk allergy?

BACKGROUND Cow's milk protein allergy (CwMPA) is the most common food allergy during early childhood and its therapy consists in the elimination of cow's milk proteins (CwMP) from the diet and the introduction of alternative formulas. Evidence about clinical use of camel's milk (CM) in CwMPA in children is scarce. The aim of this study was to determine the entity of cross-sensitization between CM and CwM in children with CwMPA. METHODS This prospective study was performed in children affected by CwMPA. We evaluated skin prick tests (SPT) for CwM, CwMP (alpha-lactalbumin [ALA], beta-lactoglobulin [BLG] and casein [CAS]) and CM and serum levels of CwM, ALA, BLG, CAS-sIgE. RESULTS Sixty-seven children with CwMPA were included in this study: twenty-one resulted SPT+ to CM. Mean wheal diameters towards raw CwM, ALA, BLG and CAS resulted significantly larger in the CM SPT+ group than in the CM SPT- group (P<0.02). Likewise, mean IgE titers against CwM, ALA and CAS were significantly higher in the CM SPT+ group than in the CM SPT-group (P<0.01). The mean wheal diameter towards raw CwM was significantly larger than that towards CM (P<0.0001). CONCLUSIONS This study confirms the presence of cross-sensitization between CwM and CM that remains lower if compared to other mammalian milks. Small wheals at the SPT towards CwM antigens together with low IgE titers against them could work as predictors in selecting patients that are expected to have negative CM SPT and then could be fed with CM with lower risks of allergic reactions.

TLR2 deficiency promotes IgE and inhibits IgG1 class-switching following ovalbumin sensitization

BackgroundTo explore the roles of Toll-like receptor (TLR)2 in Th2 cytokine production and immunoglobulin (Ig) class switching following ovalbumin (OVA) sensitization.MethodsTLR2−/− and wild-type C57BL/6 mice were sensitized by intraperitoneal injection with OVA. Lung pathology was assessed by hematoxylin and eosin staining. Abundance of interleukin (IL)4, IL5, IL13, and IL21 transcripts in the lungs was quantified by RT-PCR. OVA-specific IgG1, IgG2a, IgG2b, IgE and IgM were quantified by enzyme-linked immunosorbent assay. Phosphorylated signal transducer and activator of transcription (STAT)3 in lung tissue was detected by immunohistochemistry staining and nuclear factor (NF) κB activation was measured by immunofluorescence staining. STAT3 activation was inhibited using cryptotanshinone (CPT) treatment. Germline transcripts (Iμ-Cμ, Iγ-Cγ, Iα-Cα or Iε-Cε), post-recombination transcripts (Iμ-Cγ, Iμ-Cα or Iμ- Cε) and mature transcripts (VHDJH-Cγ, VHDJH-Cα or VHDJH-Cε) were analyzed from splenic B cells of OVA-sensitized wild-type mice (with or without CPT treatment) and TLR2−/− mice (with or without IL21 treatment).ResultsThe lungs of TLR2−/− mice showed a lesser degree of inflammation than wild-type mice after OVA sensitization. Following OVA sensitization, levels of IL4, IL13, and IL21, but not IL5, were significantly lower in TLR2−/− compared with wild-type mice. Moreover, OVA-specific IgG1 and IgE titers were markedly lower and higher, respectively, in TLR2−/− mice. TLR2 deficiency inhibited STAT3 activation but not NF-κB p65 activation. CPT treatment reduced IgG1 titers via inhibition of Stat3 phosphorylation. Both TLR2 knockout and CPT treatment reduced the frequencies of Iγ1-Cγ1, Iγ3-Cγ3 and Iα-Cα transcripts, but IL21 treatment compensated for the effects of TLR2 deficiency.ConclusionThese results suggest a role of TLR2 in restricting OVA-sensitized lung inflammation via promotion of IgG1 and inhibition of IgE class switching regulated by IL21 and STAT3.

FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression

Sialyl-Lewis x (sLex, CD15s) is a tetra-saccharide on the surface of leukocytes required for E-selectin-mediated rolling, a prerequisite for leukocytes to migrate out of the blood vessels. Here we show using flow cytometry that sLex expression on basophils and mast cell progenitors depends on fucosyltransferase 6 (FUT6). Using genetic association data analysis and qPCR, the cell type-specific defect was associated with single nucleotide polymorphisms (SNPs) in the FUT6 gene region (tagged by rs17855739 and rs778798), affecting coding sequence and/or expression level of the mRNA. Heterozygous individuals with one functional FUT6 gene harbor a mixed population of sLex+ and sLex- basophils, a phenomenon caused by random monoallelic expression (RME). Microfluidic assay demonstrated FUT6-deficient basophils rolling on E-selectin is severely impaired. FUT6 null alleles carriers exhibit elevated blood basophil counts and a reduced itch sensitivity against insect bites. FUT6-deficiency thus dampens the basophil-mediated allergic response in the periphery, evident also in lower IgE titers and reduced eosinophil counts.

Nationwide pharmacovigilance data for cetuximab-induced anaphylaxis and predictive model validation using prospective specific IgE detection

BackgroundCetuximab (chimeric monoclonal antibody to human epidermal growth factor receptor) is used to treat colorectal and head and neck cancers. Due to cross-reactivity with galactose-α-1,3-galactose (alpha-gal), it can induce hypersensitivity even at first administration. We aimed to determine the incidence and clinical manifestation of cetuximab-induced anaphylaxis, and to establish a means of predicting its incidence in patients ahead of treatment. MethodsNationwide and single-center pharmacovigilance data from 2010 to 2017 were collected from the Korea Institute of Drug Safety-Korea Adverse Event Reporting System and Severance Regional Pharmacovigilance Center. Patients scheduled for cetuximab administration were enrolled prospectively. A skin prick test was carried out and serum IgE specific to cetuximab and cross-reactive allergens were measured. Reactions were monitored after cetuximab infusion. ResultsOver 8 years, there were 23 reports of anaphylaxis nationwide. In a single-center study, incidence of cetuximab-induced anaphylaxis was 1.1%. Most anaphylaxis occurred at first injection (93.3%), even under pretreatment with anti-allergic drugs. Four of 64 patients (6.3%) experienced severe anaphylaxis. The median cetuximab-specific IgE titer was 6.9 kUA/L in patients experiencing anaphylaxis and 0 kUA/L in those who did not (P < 0.001). The results of alpha-gal, beef sIgE, and cetuximab skin prick testing were similar to those of cetuximab sIgE. Patients who did not experience hypersensitivity were negative in all 4 allergy tests. Its positive and negative predictive values were 100%. ConclusionsSpecific IgE detection of cetuximab or alpha-gal can accurately predict cetuximab-induced anaphylaxis prior to first administration.

An Exon 2-deficient isoform of the Foxp3 gene fails to protect against IgE-mediated cutaneous autoimmunity after ultraviolet light exposure.

Abstract FOXP3 is required to maintain immune tolerance, but the functional contributions of FOXP3 isoforms to the maintenance of tolerance is poorly understood. Mice express a single isoform of the Foxp3 gene, but humans encode an additional exon 2-deficient splice variant isoform of FOXP3 with no known function. To determine how exon 2 of FOXP3 contributes to Treg activity, we generated mice that only express the exon 2-deficient FoxP3 variant (called B6.FoxP3ΔExon2). In the steady-state, B6.FoxP3ΔExon2 mice develop mild autoimmunity (splenomegaly, autoantibodies and kidney nephritis) with enlarged germinal centers and elevated titers of skin-reactive IgE. We also observed skin-reactive IgE antibodies in SLE patients with active photosensivity. Therefore, We challenged B6 and B6.FoxP3ΔExon2 mouse skin with ultraviolet B (UVB) light to determine if UVB damage can increase the production of self-reactive IgE. When compared to B6 controls, B6.FoxP3ΔExon2 mice developed greater skin inflammation with increased infiltration of IgE+ plasma cells (B220lowCD138+Blimp1 +) at the site of UVB damage. B6.FoxP3ΔExon2 mice also had higher numbers of IL4-producing T effector cells (IL4+CD4+CD44+Foxp3−) and IgE-producing B cells in draining lymph nodes of UVB-challenged skin as compared to untreated control lymph nodes. Finally, UVB-treated B6.FoxP3ΔExon2 mice also had worsened kidney nephritis and proteinurea, phenocopying multi-systemic flares that occur in SLE patients with photosensitivity. Collectively, we found that exon 2 of the Foxp3 gene is required to control cutaneous inflammation though the regulation of skin-reactive IgE, and IgE-producing B cells could be targeted to limit the severity of SLE-associated photosensitivity.

Dysregulated follicular regulatory T cells and antibody responses exacerbate CNS autoimmunity

Abstract Follicular regulatory T (TFR) cells are essential for the regulation of germinal center (GC) response and humoral self-tolerance. Dysregulated follicular helper T (TFH) cell-GC-antibody (Ab) response secondary to dysfunctional TFR cells is the root of an array of autoimmune disorders. The contribution of TFR cells to the pathogenesis of multiple sclerosis (MS) and murine experimental autoimmune encephalomyelitis (EAE) remains largely unclear. Here we show that mice with a FoxP3-specific ablation of the transcription factor Blimp1 developed severe EAE and failed to recover compared to control mice, reflecting conversion of unstable regulatory T cells (Tregs) into IL-17A/GM-CSF-producing effector T-cells associated with increased TFH-Ab responses, more IgE deposition in the central nervous system (CNS) and inability to regulate CNS CD11b+ myeloid cells. Notably, serum IgE titers were positively correlated with EAE scores, and culture of CNS CD11b+ cells with sera from these EAE mice enhanced their activation, while transfer of Blimp1-deficient TFR cells promoted Ab production, activation of CNS CD11b+ cells and EAE. Moreover, compared to healthy controls, a small group of MS patients had fewer circulating Tregs and TFR cells that expressed reduced levels of Blimp1, associated with elevated serum IgE. These findings suggest that Blimp1 is essential for the maintenance of TFR cells and Ab responses in EAE, and that dysregulated TFR cells and Ab responses promote CNS autoimmunity.

Effect of triclosan on the pathogenesis of allergic diseases among children.

Few studies have assessed associations between allergic diseases and antibacterial agents in Taiwanese children. This study aimed to investigate the association of triclosan (TCS) exposure with allergic diseases among preschoolers, disease-specific IgE titers, and a child's sex. Pediatric data were obtained from the Childhood Environment and Allergic Diseases Study (CEAS; 2010) cohort, and their urine and blood samples were used to analyze TCS and IgE concentrations (age 3 group). Three years later, clinical data were obtained again from the age 3 group (age 6 group). Correlations of TCS levels at ages 3 and 6 years with IgE levels and allergic diseases were evaluated. The TCS levels were higher at age 3 than at age 6 (geometric mean, 1.05 ng/ml vs 0.37 ng/ml). TCS levels were positively correlated with serum IgE levels at ages 3 and 6 years. Asthma and atopic dermatitis were significantly associated with TCS (adjusted OR 1.14, 95% confidence interval [CI] 1.01-1.29; OR 1.22, 95% CI 1.05-1.41). Sex-stratified analysis revealed that TCS levels were positively correlated with IgE levels among boys in the age 6 group and significantly associated with asthma, allergic rhinitis, and atopic dermatitis among boys. TCS exposure is associated with IgE levels and a potentially high risk of pediatric atopic disorders.

Dysregulated follicular regulatory T cells and antibody responses exacerbate experimental autoimmune encephalomyelitis

BackgroundFollicular regulatory T (TFR) cells are essential for the regulation of germinal center (GC) response and humoral self-tolerance. Dysregulated follicular helper T (TFH) cell-GC-antibody (Ab) response secondary to dysfunctional TFR cells is the root of an array of autoimmune disorders. The contribution of TFR cells to the pathogenesis of multiple sclerosis (MS) and murine experimental autoimmune encephalomyelitis (EAE) remains largely unclear.MethodsTo determine the impact of dysregulated regulatory T cells (Tregs), TFR cells, and Ab responses on EAE, we compared the MOG-induced EAE in mice with a FoxP3-specific ablation of the transcription factor Blimp1 to control mice. In vitro co-culture assays were used to understand how Tregs and Ab regulate the activity of microglia and central nervous system (CNS)-infiltrating myeloid cells.ResultsMice with a FoxP3-specific deletion of Blimp1 developed severe EAE and failed to recover compared to control mice, reflecting conversion of Tregs into interleukin (IL)-17A/granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing effector T cells associated with increased TFH-Ab responses, more IgE deposition in the CNS, and inability to regulate CNS CD11b+ myeloid cells. Notably, serum IgE titers were positively correlated with EAE scores, and culture of CNS CD11b+ cells with sera from these EAE mice enhanced their activation, while transfer of Blimp1-deficient TFR cells promoted Ab production, activation of CNS CD11b+ cells, and EAE.ConclusionsBlimp1 is essential for the maintenance of TFR cells and Ab responses in EAE. Dysregulated TFR cells and Ab responses promote CNS autoimmunity.

Long-term impact of hymenoptera venom immunotherapy on clinical course, immune parameters, and psychosocial aspects.

Background: Venom immunotherapy (VIT) is highly efficient in subjects suffering from IgE-mediated allergy to hymenoptera venom (HV), and VIT results in substantial improvement of quality of life (QoL). However, VIT-induced tolerance may be lost over time after cessation of treatment, putting patients at risk of re-sting anaphylaxis. Materials and methods: To study the effect of VIT on maintenance of HV tolerance we evaluated the natural history of 54 patients who were treated with VIT up to 29 years ago, with a special focus on re-stings and their subsequent course. Furthermore, we analyzed HV-specific IgE, IgG, and IgG4 antibody titers. Finally, we assessed the long-term impact of VIT on various psychosocial aspects like dealing with hymenoptera exposures, daily life activities, self-assurance, and personal environment. Results: 29 (53.7%) subjects experienced at least one re-sting after stopping VIT, with 23 (79%) showing no systemic reaction (SR). Eleven of these (37.9%) took emergency drugs as a safety measurement. Six individuals (21%) showed loss of tolerance experiencing an anaphylactic reaction. No difference in HV-specific IgE, IgG4, or IgG antibody concentrations was noticed among the different patients. Subjects who tolerated a re-sting without applying emergency drugs felt least affected in their social-behavioral leisure activities when hymenoptera were around or by anxiety for new stings. Conclusion: VIT leads to long-term tolerance in the majority of HV-allergic patients, however, ~ 1/5 may lose protection over time, arguing for continued follow-up on VIT-treated subjects and keeping them equipped with an emergency kit. Notably, VIT also results in a lasting, strong impact on self-assurance and sense of well-being in individuals who tolerated a re-sting without employing emergency drugs, which emphasizes the need to use them only in case of systemic symptoms after stopping successful VIT.

Threshold dose of cow's milk in sensitization to casein higher than those of casein and β-lactoglobulin in children with cow's milk allergy.

Recent treatment for food allergies involves the intake of allergy-causing foods at doses lower than the threshold dose determined by the oral food challenge (OFC). For a more successful treatment, it is necessary to identify a biomarker to establish safer doses of allergens in foods consumed at home. In this study, we aim to investigate whether the pattern of sensitization to cow's milk (CM) is related to the threshold dose of CM. Fifty patients with sensitization to casein (casein-specific IgE titer ≥ 0.7 UA/ml) and who have undergone the CM OFC test from July 2013 to July 2015 were enrolled. They were examined for the presence or absence of sensitization to β-lactoglobulin (BLG) (BLG-specific IgE ≥ 0.7 UA/ml). They were divided into two groups, namely, the only-casein-specific IgE-positive (C) group, and both casein- and BLG-specific IgE-positive (C + B) group. The C group had 26 patients and the C + B group had 24. Both the CM- and casein-specific IgE titers were higher in the C + B group than in the C group. The positivity rates determined from OFC test results were 53.8 and 87.5%, and the threshold doses of CM were 88.7 and 31.1 ml in the C and C + B groups, respectively. In patients with low casein-specific IgE titers (≤ 10 UA/ml), the C + B group showed a significantly lower threshold dose of CM than the C group. Our results suggest that children with CM allergy sensitized to casein alone have a higher threshold dose than those sensitized to both casein and BLG.

Carvone Enantiomers Differentially Modulate IgE-Mediated Airway Inflammation in Mice.

Carvone is a monoterpene found in nature in the form of enantiomers (S- and R-). While previous research has demonstrated the anti-inflammatory and anti-allergic effects of carvone, the influence of carvone enantiomeric composition on its anti-allergic activity remains to be investigated. This study aimed to evaluate the anti-allergic activity of carvone enantiomers in a murine model of airway allergic inflammation induced by sensitization and challenge with ovalbumin (OVA). The oral treatment with R-carvone or S-carvone 1 h before each challenge inhibited the number of leukocytes and eosinophils in the bronchoalveolar lavage (BAL). R-carvone inhibited leukocyte infiltration and mucus production in the lung, which was correlated with decreased production of OVA-specific IgE in the serum and increased concentrations of IL-10 in the BAL. On the other hand, the administration of S-carvone had little inhibitory effect on inflammatory infiltration and mucus production in the lung, which might be associated with increased production of IFN-γ in the BAL. When administered 1 h before each sensitization, both enantiomers inhibited eosinophil recruitment to the BAL but failed in decreasing the titers of IgE in the serum of allergic mice. Our data indicate that carvone enantiomers differentially modulated IgE-mediated airway inflammation in mice. In conclusion, unlike S-carvone, R-carvone has the potential to be used in anti-allergic drug development.

IgE autoantibodies in serum and skin of non-bullous and bullous pemphigoid patients.

BackgroundNon‐bullous pemphigoid (NBP) is a pemphigoid variant which frequently resembles other pruritic skin diseases. In contrast with bullous pemphigoid (BP), blisters are absent. In BP, previous studies showed that IgE autoantibodies may be involved in its pathogenesis. IgE‐activated mast cells, basophils and eosinophils may participate in BP by inducing pruritus and possibly blister formation, although the differential role of IgE in NBP compared with BP has not yet been described.ObjectiveTo assess IgE in serum and skin of NBP and BP patients.MethodsWe examined total IgE and pemphigoid‐specific IgE in the serum of 68 NBP and 50 BP patients by enzyme‐linked immunosorbent assay (ELISA). Sera of 25 pemphigus patients and 25 elderly patients with pruritus were included as controls. Skin biopsies of 14 NBP and 14 BP patients with the highest IgE titres to NC16A were stained for IgE by immunofluorescence techniques.ResultsTotal IgE was elevated in 63% of NBP and 60% of BP patients, and in 20% of pemphigus controls, as well as 60% of elderly controls. IgE ELISAs were more frequently positive in BP than in NBP (NC16A 18% vs. 9%, P = 0.139; BP230 34% vs. 22%, P = 0.149). IgE ELISAs for NC16A and BP230 were positive in 8% and 20% of elderly controls, respectively, while all pemphigus controls were negative. Two of 28 biopsies (7%; one NBP, one BP) showed linear IgE along the basement membrane zone, while in most biopsies (71% NBP; 86% BP) IgE was bound to dermal cells.ConclusionSince IgE was present in the serum and skin of both NBP and BP patients, this supports IgE‐dependent mechanisms common to both diseases, such as pruritus. However, it remains to be elucidated whether IgE contributes to blister formation in BP.

The antibody response to the glycan α‐Gal correlates with COVID‐19 disease symptoms

The coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has affected millions of people worldwide. Characterization of the immunological mechanisms involved in disease symptomatology and protective response is important to progress in disease control and prevention. Humans evolved by losing the capacity to synthesize the glycan Galα1‐3Galβ1‐(3)4GlcNAc‐R (α‐Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti‐α‐Gal immunoglobulin M (IgM)/IgG antibodies produced in response to bacterial microbiota. In addition to anti‐α‐Gal antibody‐mediated pathogen opsonization, this glycan induces various immune mechanisms that have shown protection in animal models against infectious diseases without inflammatory responses. In this study, we hypothesized that the immune response to α‐Gal may contribute to the control of COVID‐19. To address this hypothesis, we characterized the antibody response to α‐Gal in patients at different stages of COVID‐19 and in comparison with healthy control individuals. The results showed that while the inflammatory response and the anti‐SARS‐CoV‐2 (Spike) IgG antibody titers increased, reduction in anti‐α‐Gal IgE, IgM, and IgG antibody titers and alteration of anti‐α‐Gal antibody isotype composition correlated with COVID‐19 severity. The results suggested that the inhibition of the α‐Gal‐induced immune response may translate into more aggressive viremia and severe disease inflammatory symptoms. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with α‐Gal epitopes to modify the microbiota and increase α‐Gal‐induced protective immune response and reduce severity of COVID‐19.

S3011 Recurring Gastrointestinal Symptoms as a Novel Presentation of Alpha-Gal Allergy

INTRODUCTION: Galactose-alpha-1,3-galactose (alpha-gal) allergy is a delayed allergy after ingestion of mammalian meat such as beef, pork, or lamb. In the literature, symptoms range from urticaria to anaphylaxis with concomitant gastrointestinal manifestations. There are no case reports of adults with abdominal pain as the sole symptom of this allergy. This case delineates a novel presentation of the alpha-gal allergy with a patient with only gastrointestinal symptoms. CASE DESCRIPTION/METHODS: A 46 year old male with a past medical history of hypothyroidism, gastroesophageal reflux disease, hypertriglyceridemia, seasonal allergies and asthma presented with abdominal pain. His first episode occurred two years ago after the ingestion of prime rib, at which time he developed abdominal pain, nausea, and vomiting. Subsequently, he noticed abdominal pain after eating any red meat. Each abdominal pain episode was stabbing in quality and generally lasted two hours. Additional history revealed tick-exposure prior to the first episode of symptoms. Workup confirmed an allergy to beef with an elevated beef alpha-gal IgE of 0.71 kU/L (reference range, <0.35 kU/L). IgE levels were within normal range for pork and lamb. After eliminating all mammalian meat from the diet, the patient’s symptoms resolved. DISCUSSION: The first alpha-gal allergy to mammalian meat was documented in 2006 and it is still not fully understood. It is proposed that remnant alpha-gal from previous mammalian blood meals are transmitted to humans through the saliva of Amblyomma americanum (lone star tick), which is endemic to the southwest region of the United States. After ingestion of mammalian meat containing alpha-gal, the alpha-gal, found in glycolipids, is packaged into chylomicrons. It is released into the thoracic duct and IgE is deployed. It is suspected that this prolonged pathway is why symptoms do not manifest until 3 to 8 hours after ingestion. It is crucial to obtain a good clinical history and recognize that recurrent abdominal pain, nausea or vomiting may be the only presentation especially given that the current mean time to diagnosis is 7.1 years. Diagnosis is made with blood work assessing IgE levels to beef, pork, and lamb. Elevation of IgE titers to only one mammalian meat is required for diagnosis. Given the risk of anaphylaxis, prescription of an epinephrine pen and elimination of mammalian meat is the only treatment.

Evaluation of the LDBio Aspergillus ICT lateral flow assay for serodiagnosis of allergic bronchopulmonary aspergillosis.

Early recognition and diagnosis of allergic bronchopulmonary aspergillosis (ABPA) is critical to improve patient symptoms, and antifungal therapy may prevent or delay progression of bronchiectasis and development of chronic pulmonary aspergillosis. A recently commercialized lateral flow assay (Aspergillus ICT) (LDBio Diagnostics, Lyons, France) detects Aspergillus-specific antibodies in <30 minutes, requiring minimal laboratory equipment. We evaluated this assay for diagnosis of ABPA compared to diseased (asthma and/or bronchiectasis) controls. ABPA and control sera collected at the National Aspergillosis Centre (Manchester, UK) and/or from the Manchester Allergy, Respiratory and Thoracic Surgery research biobank were evaluated using the Aspergillus ICT assay. Results were read both visually and digitally (using a lateral flow reader). Serological Aspergillus-specific IgG and IgE, and total IgE titres were measured by ImmunoCAP. For 106 cases of ABPA versus all diseased controls, sensitivity and specificity for the Aspergillus ICT were 90.6% and 87.2%, respectively. Sensitivity for 'proven' ABPA alone (n = 96) was 89.8%, and 94.4% for 'presumed' ABPA (n = 18). 'Asthma only' controls (no bronchiectasis) and 'bronchiectasis controls' exhibited 91.4% and 81.7% specificity, respectively. Comparison of Aspergillus ICT result with Aspergillus-specific IgG and IgE titres showed no evident immunoglobulin isotype bias. Digital measurements displayed no correlation between ImmunoCAP Aspergillus-specific IgE level and ICT test line intensity. The Aspergillus ICT assay exhibits good sensitivity for ABPA serological screening. It is easy to perform and interpret, using minimal equipment and resources; and provides a valuable simple screening resource to rapidly distinguish more serious respiratory conditions from Aspergillus sensitization alone.