World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation

Jensen, Sebastian A.; Fiocchi, Alessandro; Baars, Ton; Jordakieva, Galateja; Nowak‐Węgrzyn, Anna; Pali‐Schöll, Isabella; Passanisi, Stefano; Pranger, Christina L.; Roth‐Walter, Franziska; Takkinen, Kristiina; Assa’ad, Amal; Venter, Carina; Jensen‐Jarolim, Erika

doi:10.1016/j.waojou.2022.100668

Cited by 21 publications

(15 citation statements)

References 114 publications

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“…When this site is empty, Bos d 5 promotes the expression of CD4 on helper T cells and increased production of the T2 cytokines IL‐10 and IL‐13 compared to a “loaded” site where there was a decreased CD4+ expression 38,39 . It was previously hypothesized that milk processing alters the hydrophobic binding site on Bos d 5 making it more immunogenic 40,41 . Further studies are needed to examine the potential‐specific role of Bos d 5 since this seems to be the dominant antigenic component of cow's milk and more than half of EoE patients respond to cow's milk protein elimination diet 18 …”

Section: Discussionmentioning

confidence: 99%

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Immunoglobulin G4 in eosinophilic esophagitis: Immune complex formation and correlation with disease activity

Medernach

Zhao

et al. 2023

Allergy

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BackgroundRecent studies have shown deposition of immunoglobulin G4 (IgG4) and food proteins in the esophageal mucosa of eosinophilic esophagitis (EoE) patients. Our aims were to assess whether co‐localization of IgG4 and major cow's milk proteins (CMPs) was associated with EoE disease activity and to investigate the proteins enriched in proximity to IgG4 deposits.MethodsThis study included adult subjects with EoE (n = 13) and non‐EoE controls (n = 5). Esophageal biopsies were immunofluorescence stained for IgG4 and CMPs. Co‐localization in paired samples from active disease and remission was assessed and compared to controls. The proteome surrounding IgG4 deposits was evaluated by the novel technique, AutoSTOMP. IgG4‐food protein interactions were confirmed with co‐immunoprecipitation and mass spectrometry.ResultsIgG4‐CMP co‐localization was higher in the active EoE group compared to paired remission samples (Bos d 4, p = .02; Bos d 5, p = .002; Bos d 8, p = .002). Co‐localization was also significantly higher in the active EoE group compared to non‐EoE controls (Bos d 4, p = .0013; Bos d 5, p = .0007; Bos d 8, p = .0013). AutoSTOMP identified eosinophil‐derived proteins (PRG 2 and 3, EPX, RNASE3) and calpain‐14 in IgG4‐enriched areas. Co‐immunoprecipitation and mass spectrometry confirmed IgG4 binding to multiple food allergens.ConclusionThese findings further contribute to the understanding of the interaction of IgG4 with food antigens as it relates to EoE disease activity. These data strongly suggest the immune complex formation of IgG4 and major cow's milk proteins. These immune complexes may have a potential role in the pathophysiology of EoE by contributing to eosinophil activation and disease progression.

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Section: Discussionmentioning

confidence: 99%

“…38,39 It was previously hypothesized that milk processing alters the hydrophobic binding site on Bos d 5 making it more immunogenic. 40,41 AutoSTOMP is a novel technology that allows for spatial analysis of the proteome surrounding IgG4 deposits in the esophagus.…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin G4 in eosinophilic esophagitis: Immune complex formation and correlation with disease activity

Medernach

Zhao

et al. 2023

Allergy

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“…Another intriguing result concerned the lack of the OIT effect on allergen-specific IgE in milk molecules. OIT probably acts on tolerogenic mechanisms, independent from a type 2 response, but involving Breg and Treg cells as actors of natural immunotolerance [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Oral Immunotherapy for Children with Cow’s Milk Allergy: A Practical Approach

et al. 2022

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Cow milk allergy (CMA) is a prevalent disease in childhood. Natural history is usually favorable as CMA can disappear by school age in many subjects. Diagnosis corresponds to treatment, as an elimination diet is a solution. However, cow’s milk (CM) is real food, hardly replaceable. Thus, CM reintroduction represents a demanding challenge in clinical practice. The induction of CM tolerance could be achievable using oral immunotherapy (OIT), such as the administration of increasing milk quantities until reaching tolerance. However, the OIT schedule and procedure need to be better standardized, and performance may vary widely. Therefore, the present study reports the practical experience of a third-level pediatric allergy center in managing children with CMA and submitting them to OIT. OFC and OIT are relatively safe procedures as the reaction rate is low. Almost two-thirds of the OIT subjects tolerated CM. Reactions were associated with high IgE levels. Therefore, the present experience, developed by a qualified center, may suggest and propose a practical approach for managing children with CMA. After the initial workup, including a thorough history, physical examination, and laboratory tests, OFC and, when indicated, OIT could be performed in most children with CMA.

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“…CMPA affects approximately 8%of infants and young children. After egg, peanut, and fish allergies, it is the fourth-most common food allergy in babies [4].…”

Section: Introductionmentioning

confidence: 99%

“…A variety of factors may play a role in the complex development of food allergies. A disruption in the development of oral tolerance has been observed in infants with food allergies, characterized by defects in the induction of regulatory T cells, and the production of allergen-specific neutralizing IgA antibodies [4]. Furthermore, even though the specific properties of the allergens themselves contribute to the degree of allergenicity, defects in the epithelial barrier, both in the skin and in the intestine, as well as changes in the pH of the stomach are thought to promote allergy.…”

Section: Introductionmentioning

confidence: 99%

Probiotic Bacteria from Human Milk Can Alleviate Oral Bovine Casein Sensitization in Juvenile Wistar Rats

et al. 2023

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This study aims to see if probiotic bacteria from human milk could ameliorate oral cow’s milk sensitization. The probiotic potential of the SL42 strain isolated from the milk of a healthy young mother was first determined. Rats were then randomly gavaged with cow’s milk casein without an adjuvant or assigned to the control group. Each group was further subdivided into three groups, with each receiving only Limosilactobacillus reuteri DSM 17938, SL42, or a phosphate-buffered saline solution. Body weight, temperature, eosinophils, serum milk casein-specific IgE (CAS-IgE), histamine, and serum S100A8/A9 and inflammatory cytokine concentrations were measured. The animals were sacrificed after 59 days; histological sections were prepared, and the spleen or thymus weights, as well as the diversity of the gut microbiota, were measured. On days 1 and 59, SL42 abridged systemic allergic responses to casein by dropping histamine levels (25.7%), CAS-specific IgE levels (53.6%), eosinophil numbers (17%), S100A8/9 (18.7%), and cytokine concentrations (25.4–48.5%). Analyses of histological sections of the jejunum confirmed the protective effect of probiotic bacteria in the CAS-challenged groups. Lactic acid bacteria and Clostridia species were also increased in all probiotic-treated groups. These findings suggest that probiotics derived from human milk could be used to alleviate cow’s milk casein allergy.

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World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation

Cited by 21 publications

References 114 publications

Immunoglobulin G4 in eosinophilic esophagitis: Immune complex formation and correlation with disease activity

Immunoglobulin G4 in eosinophilic esophagitis: Immune complex formation and correlation with disease activity

Oral Immunotherapy for Children with Cow’s Milk Allergy: A Practical Approach

Probiotic Bacteria from Human Milk Can Alleviate Oral Bovine Casein Sensitization in Juvenile Wistar Rats

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