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Peanut oral immunotherapy (POIT) has a key role as a treatment option in peanut-allergic patients, with demonstrated safety and efficacy in research trials. METHODS: We assessed the eligibility of patients who expressed an interest in undertaking POIT in our allergy clinic over a period of 2.5 years. Our goal was to identify appropriate candidates for this therapy and examine reasons for non-participation. RESULTS: One hundred and seventy-four patients were evaluated over a period of 2.5 years (January 2018 -July 2020). Median age was 8 years (IQR 5.25-11), 104 were male (60%) and 70 (40%) were female. Of these, 138 (79%) had concomitant food allergy, with 36 (21%) having peanut allergy only, 136 (78%) had associated atopic dermatitis (AD), 79 (45%) asthma, and 145 (83%) allergic rhinitis (AR). A total of 24 patients were not eligible for POIT. The main reasons included: uncontrolled asthma (1), uncontrolled allergic rhinitis (1), aeroallergen immunotherapy build-up period (1), severe atopic dermatitis (1), Crohn's disease (2), undiagnosed abdominal migraines (1), eosinophilic esophagitis (1), undiagnosed chronic gastrointestinal symptoms (2), infant age (1), concerns over inconsistent epinephrine carriage (1), negative peanut oral challenge (1), unconfirmed peanut allergy diagnosis (2), inability to adhere to exercise restrictions associated with therapy or regular up-dosing appointments (2), severe anxiety/depression (2), financial issues (5). CONCLUSION: Identifying appropriate candidates for POIT is crucial for the success of this intervention and for ensuring safety of participating patients. Practicing clinicians should evaluate patients carefully and thoroughly prior to initiating POIT.

Allergen-specific immunotherapy (IT) induces tolerance in food allergy. Immunological changes during IT have been investigated, however little work has looked at global gene-expression changes. We have developed a tolerance-model of peach allergy using a novel system of sublingual IT (SLIT) based on glycodendropeptides. We analysed changes in dendritic cells (DCs) from mice receiving SLIT. METHODS: RNA-Seq was used to profile transcriptional changes in lymph node DCs for mice from two groups: anaphylactic mice treated with 2nM SLIT (tolerant), anaphylactic mice treated with 5nM SLIT (desensitized) and two controls: sensitized and anaphylactic mice. Mice were challenged intraperitoneally with Pru p 3, then sacrificed. Poly(A) enriched RNA sequencing was performed using Illumina HiSeq (100bp, paired end); sequences were aligned to the mouse genome using STAR. Differential expression analysis was performed using DESeq2 and functional enrichment analysis using TopGO. RESULTS: Gene expression for the sensitized, desensitized and tolerant mice groups were compared with anaphylactic samples. Sensitized mice showed the largest number of changes, followed by desensitized, then tolerant mice. Nevertheless, there was a set of core genes that changed in all comparisons. In terms of functional enrichment analysis, there was an overrepresentation of genes involved in the innate immune response, regulation of T-cell proliferation and TNF signaling. Interestingly, genes belonging to the MHC-II complex showed altered expression in different groups. CONCLUSIONS: By exploring gene expression at the global level we are able to obtain insights into the transcriptional changes and cellular processes that occur during immunotherapy. Future work is needed to further investigate these changes.

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Intestinal microbiome supports immune homeostasis. Segmental filamentous bacteria (SFB) induce differentiation of Th17-cells in enteric-associated lymphoid tissue (GALT). Clostridium (cluster IV and XIVa) and Bacteroidesfragilis (polysaccharide A) stimulate the formation of T-regulatory cells (Treg) and production of suppressor cytokine IL-10. METHODS: Metabolites of B. fragilis, short-chain fatty acids (SCFA), activate GALT cells through the FFAR2 receptor. Decrease in the concentration of SCFA decreases the number of Treg and disrupts the balance of Th17/Treg, which leads decreased level of FFAR2, Foxp3 mRNA and an increase in RORgt in GALT. Vancomycin and salmonella were given to rats and the levels of SFB assessed. RESULTS: SFB increased and A.muciniphila, F.prausnitzii decreased post Vancomycin and salmmonella. In rats infected with salmonella after pretreatment with vancomycin, the number of SFBs increased with a marked decrease in the Bacteroides-Prevotela group, A.muciniphila, Clostridium spp. clusters XIV, IV, and F.prausnitzii, leading to a decrease in the expression level of Foxp3 + gene mRNA and an increase in Rorgt +. The introduction of B. fragilis to animals receiving Salmonella on the background of pre-treatment with vancomycin caused a decrease in the level of SFB and mRNA of Rorgt +, and, conversely, increased the number of Bacteroides-Prevotela group, A.muciniphila, Clostridium spp. clusters XIV, IV, F.prausnitzii and expression of Foxp3 + genes, indicative of restoration of intestinal microbiome homeostasis. CONCLUSIONS: Salmonella-induced changes in immunoregulatory bacteria impacts transcriptional activity of the Foxp3 and Roryt genes in rat GALT.