Trends in egg specific immunoglobulin levels during natural tolerance and oral immunotherapy.
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ABSTRACT:
SUBMITTER: Andorf S
PROVIDER: S-EPMC7220838 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImmunoglobulinA (IgA) is the predominant antibody isotype in the gut, where it regulates commensal flora and neutralizes toxins and pathogens. The function of food-specific IgA in the gut is unknown but is presumed to protect from food allergy. Specifically, it has been hypothesized that food-specific IgA binds ingested allergens and promotes tolerance by immune exclusion; however, the evidence to support this hypothesis is indirect and mixed. Although it is known that healthy adults have peanut-specific IgA in the gut, it is unclear whether children also have gut peanut-specific IgA. We found in a cohort of non-food-allergic infants (n = 112) that there is detectable stool peanut-specific IgA that is similar to adult quantities of gut peanut-specific IgA. To investigate whether this peanut-specific IgA is associated with peanut tolerance, we examined a separate cohort of atopic children (n = 441) and found that gut peanut-specific IgA does not predict protection from development of future peanut allergy in infants nor does it correlate with concurrent oral tolerance of peanut in older children. We observed higher plasma peanut-specific IgA in those with peanut allergy. Similarly, egg white-specific IgA was detectable in infant stools and did not predict egg tolerance or outgrowth of egg allergy. Bead-based epitope assay analysis of gut peanut-specific IgA revealed similar epitope specificity between children with peanut allergy and those without; however, gut peanut-specific IgA and plasma peanut-specific IgE had different epitope specificities. These findings call into question the presumed protective role of food-specific IgA in food allergy.
| S-EPMC10219469 | biostudies-literature
Project description:BackgroundHen's egg allergy is among the most common food allergies in childhood and predicts later development of allergic disease. The optimal efficacy and mechanism(s) of egg allergen immunotherapy are poorly understood.ObjectiveTo enhance immunologic and clinical outcomes of egg oral immunotherapy (OIT) using a conditionally increased dosing strategy.MethodsIn an open-label clinical trial of egg OIT, egg-allergic children ingested daily doses of egg protein that were gradually increased based on the egg white (EW) IgE level. Skin prick test reactivity and EW- and ovomucoid-specific cellular and humoral responses were measured longitudinally. To confirm clinical tolerance, patients underwent double-blinded, placebo-controlled food challenges 1 month after completing the dosing protocol.ResultsChildren aged 3 to 13 years with characteristics of clinical egg allergy were enrolled. All 6 patients who completed the entire protocol developed clinical tolerance to egg during the study. The median wheal diameter on EW skin prick testing decreased from 10 to 2.5 mm during OIT (P = .03). Both EW and ovomucoid IgE levels significantly decreased during the study (median EW IgE level: from 18.8 kU/L at baseline to 3.9 kU/L, P = .03), and corresponding IgG4 levels increased (median EW IgG4 level: from 0.65 mg/L at baseline to 86.15 mg/L, P = .03). Transient increases were seen in egg-induced interleukin 10 (P = .06) and transforming growth factor β (P = .18) levels, and the ratio of T(H)2:T(H)1 cytokine production was decreased (P = .25).ConclusionsEgg OIT is associated with tolerance acquisition in children with persistent egg allergy. Individualized dosing regimens may be necessary to achieve a full therapeutic effect in some patients.
| S-EPMC3026291 | biostudies-literature
Project description:The aim of this study was to characterize of chicken egg yolk immunoglobulins (IgYs) specific as immunotherapy to Mycobacterium tuberculosis complex (MTBC) infection. Lohmann laying hens were immunized intramuscularly with antigenic of MTBC. Egg yolk was separated from egg white, and IgY antibody was then purified by multiple polyethylene glycols 6000 extraction and ammonium sulfate purification steps. The IgY anti-MTBC concentration in egg yolk increased at 2 weeks and it reached a maximum at 4 weeks after immunization. After 6 weeks, the levels of IgY anti-MTBC decreased gradually. The antibody of MTBC was detected and produces a specific line of precipitation in agar gel precipitation test beginning the week 2 after the first immunization. Analysis of results obtained with ELISA showed a significant increase in the MTBC specific antibodies after 2 weeks and reached a plateau at 4 weeks from the booster immunization. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the IgY preparation to be pure and dissociated into protein bands with molecular weights of 112, 78, 69, 49, and 28 kDa and Western blot analysis shown the presence of anti-MTBC IgY in egg yolks, with molecular weights of approximately 78 kDa. These results suggested that egg yolk could be a practical strategy in large-scale production of specific anti-MTBC IgY for immunotherapy of TBC.
| S-EPMC5527699 | biostudies-other
Project description: Not available
| S-EPMC6494514 | biostudies-literature
Project description:BackgroundBronchial hyperresponsiveness (BHR) and asthma are frequently present in children with food allergy. We assessed BHR in children receiving oral immunotherapy (OIT) for persistent egg or peanut allergy and examined whether OIT affects asthma control.MethodsMethacholine challenge testing was performed in 89 children with persistent egg or peanut allergy diagnosed by double-blind, placebo-controlled food challenge and 80 control children without food allergy. Of the 89 food-allergic children, 50 started OIT for egg allergy and 39 for peanut allergy. Sensitization to aeroallergens was evaluated by skin prick testing. Forty of the 89 children with regular controller treatment for asthma underwent methacholine challenge testing and 34 measurement of exhaled nitric oxide (FeNO) at baseline and after 6-12 months of OIT.ResultsMethacholine challenge testing revealed significant BHR in 29/50 children (58%) with egg allergy, 15/39 children (38%) with peanut allergy, and 6/80 controls (7.5%). The mean cumulative dose of methacholine causing a 20% fall in FEV1 differed significantly between the egg and peanut-allergic versus the control children (1009 μg, 1104 μg, and 2068 μg, respectively, p < 0.001). Egg or peanut OIT did not affect lung function, the degree of BHR or FeNO levels in children with asthma and had no adverse effect on asthma control. Lung function or BHR did not associate with the OIT outcome.ConclusionBHR was significantly more frequent in children with persistent egg or peanut allergy than in children without food allergy. Oral immunotherapy did not increase BHR and was safe for children on regular asthma medication.
| S-EPMC9549178 | biostudies-literature
Project description:The incidence of food allergy, a disease characterized by adverse immune responses that can render common foods life-threatening, is rising. Yet our current standard of care is simply avoidance of allergenic foods and administration of emergency medications upon accidental exposure. Significant advances have been made in food allergy oral immunotherapy, which is emerging as a potential preventive and curative treatment for this disease. The fundamental strategy of oral immunotherapy is to mitigate adverse immune responses to allergenic food proteins through repeated exposure; reduced reactivity to food allergens (desensitization) often results, but the establishment of sustained immune unresponsiveness or of permanent resolution (tolerance) is not certain. This review examines exciting recent developments in oral immunotherapy for food allergy.
| S-EPMC5178145 | biostudies-other
Project description:BackgroundFor egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy.MethodsIn this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months.ResultsAfter 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months.ConclusionsThese results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.).
| S-EPMC3424505 | biostudies-literature
Project description:BackgroundWhile desensitization and sustained unresponsiveness (SU) have been shown with egg oral immunotherapy (OIT), the benefits of baked egg (BE) therapy for egg allergy have not been well studied.ObjectivesThis study sought to evaluate the safety and efficacy of BE ingestion compared with egg OIT in participants allergic to unbaked egg but tolerant to BE.MethodsChildren who are BE-tolerant but unbaked egg reactive ages 3 to 16 years were randomized to 2 years of treatment with either BE or egg OIT. Double-blind, placebo-controlled food challenges were conducted after 1 and 2 years of treatment to assess for desensitization, and after 2 years of treatment followed by 8 to 10 weeks off of treatment to assess for SU. Mechanistic studies were conducted to assess for immune modulation. A cohort of participants who are BE-reactive underwent egg OIT and identical double-blind, placebo-controlled food challenges as a comparator group.ResultsFifty participants (median age 7.3 years) were randomized and initiated treatment. SU was achieved in 3 of 27 participants assigned to BE (11.1%) versus 10 of 23 participants assigned to egg OIT (43.5%) (P = .009). In the BE-reactive comparator group, 7 of 39 participants (17.9%) achieved SU. More participants who are BE-tolerant withdrew from BE versus from egg OIT (29.6% vs 13%). Dosing symptom frequency in participants who are BE-tolerant was similar with BE and egg OIT, but more frequent in participants who are BE-reactive. Egg white-specific IgE, skin testing, and basophil activation decreased similarly after BE and egg OIT.ConclusionsAmong children allergic to unbaked egg but tolerant to BE, those treated with egg OIT were significantly more likely to achieve SU than were children ingesting BE.
| S-EPMC7554054 | biostudies-literature
Project description:With the growing emergence of pan-drug-resistant Acinetobacter baumannii (PDR-Ab) strains in clinical, new strategies for the treatment of PDR-Ab infections are urgently needed. Egg yolk immunoglobulin (IgY) as a convenient and inexpensive antibody has been widely applied to the therapy of infectious diseases. The aim of this study was to produce IgY specific to PDR-Ab and investigate its antibacterial effects in vitro and in vivo. IgYs specific to two PDR-Ab strains were produced by immunizing hens with formaldehyde inactivated PDR-Ab cells and isolated from yolks with a purity of 90% by water dilution, salt precipitations and ultrafiltration. IgYs showed high titers when subjected to an ELISA and inhibited the growth of PDR-Ab in a dose-dependent manner in liquid medium. Scanning electron microscopy assay showed structural modification and aggregation of PDR-Ab treated with specific IgYs. Freshly cultured PDR-Ab cells were nasally inhaled in BALB/c mice to induce acute pneumonia. The infected mice were intraperitoneally injected with specific IgYs using cefoperazone/sulbactam and dexamethasone as positive controls. The IgYs specific to PDR-Ab lowered the mortality of mice with PDR-Ab-induced acute pneumonia, decreased the level of TNF-α and IL-1β in serum and reduced inflammation in lung tissue. Specific IgY has the potential to be used as a new therapeutic approach for the treatment of A. baumannii-induced infections.
| S-EPMC7126593 | biostudies-literature
Project description:We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1-4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.
| S-EPMC8714802 | biostudies-literature