Immunoglobulin-coating patterns reveal altered humoral responses to gut bacteria in pediatric cow milk allergies.

Autor: Augustine T; Laboratory of Immunoregulation, Sidra Medicine, Doha, Qatar., Murugesan S; Microbiome and Host-Microbes Interactions Laboratory, Sidra Medicine, Doha, Qatar., Badri F; Laboratory of Immunoregulation, Sidra Medicine, Doha, Qatar., Gentilcore G; Deep Phenotyping Core, Sidra Medicine, Doha, Qatar., Grivel JC; Deep Phenotyping Core, Sidra Medicine, Doha, Qatar., Akobeng A; Department of Gastroenterology, Sidra Medicine, Doha, Qatar., Elawad M; Department of Gastroenterology, Sidra Medicine, Doha, Qatar., Adeli M; Department of Allergy/Immunology, Sidra Medicine, Doha, Qatar., Al Khodor S; Microbiome and Host-Microbes Interactions Laboratory, Sidra Medicine, Doha, Qatar., van Panhuys N; Laboratory of Immunoregulation, Sidra Medicine, Doha, Qatar. nvanpanhuys@sidra.org.
Jazyk: angličtina
Zdroj: Journal of translational medicine [J Transl Med] 2024 Nov 12; Vol. 22 (1), pp. 1021. Date of Electronic Publication: 2024 Nov 12.
DOI: 10.1186/s12967-024-05850-z
Abstrakt: Background: Pediatric cow milk allergies (CMA) can occur in immunoglobulin (Ig) E and non-IgE-mediated forms. Unlike IgE-mediated allergies, the mechanisms of disease pathogenesis in non-IgE-mediated food allergy and an association with microbiome has not been well established. Previous studies have identified the presence of altered humoral responses to gut bacteria in IgE mediated allergies. Here, we analyzed IgA, IgE and IgG responses to gut bacteria in subjects with either IgE or non-IgE mediated CMA to identify relative proportions of Ig-coated bacteria and characterize unique disease specific microbial signatures.
Methods: Multi-parametric flow cytometry analysis was used to identify IgA, IgE and IgG responses to gut bacteria in CMA patients. Cell sorting of Ig coated gut bacteria was subsequently performed followed by high throughput 16S rRNA gene sequencing and specific patterns of humoral responses to gut bacteria assessed in each study group.
Results: We identified significant alterations in IgA and IgG gut bacterial coating patterns in CMA subjects. Proportions of IgA-coated bacteria were decreased in IgE mediated CMA subjects without atopic dermatitis (ALL) and non-IgE mediated CMA subjects (ENP), compared to healthy controls (CON). In comparison, IgG-coated bacteria was significantly elevated in CMA subjects with atopic dermatitis (AD). Alpha and beta diversities displayed significant differences in IgA-, IgE-, and IgG-coated bacteria in AD and ENP groups. Significant differences in bacteria coated by IgA, IgE and IgG were detected at Phyla, Genus and Species levels and associated bacterial dysbiosis in IgE and non-IgE mediated allergies were identified. Linear discriminant analysis (LDA) effect size (LEFse) revealed unique disease associated bacterial signatures, including several pathogenic bacteria namely Bacteroides fragilis, Ruminococcus gnavus, Eubacterium dolichum, Fusobacterium, Clostridium neonatale and Robinsoniella peoriensis. Receiver operating characteristic curve analysis confirmed the efficiency of using the bacterial signatures identified as biomarkers for disease.
Conclusions: Altered IgA and IgG responses to gut bacteria were identified in CMA subjects. The disease-specific responses were associated with alterations in bacterial diversity and concomitant dysbiosis of Ig-coated bacteria in IgE-mediated and non-IgE-mediated CMA pediatric subjects. The identification of pathogenic bacteria uniquely associated with different classes of allergic disease indicates a role of these bacteria in driving disease-specific pathological phenotypes.
Competing Interests: Declarations Ethics approval and consent to participate The study obtained written parental consent from all participants before enrollment. The study protocol (1500751) was approved by the Institutional Review Board (IRB) at Sidra Medicine, Doha, Qatar Consent for publication Not applicable. Competing interests The authors declare no competing financial or non-financial interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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