Update on Food Protein-Induced Enterocolitis Syndrome (FPIES).

PURPOSE OF REVIEW: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by delayed, and potentially severe, gastrointestinal symptoms. Since the advent of a specific diagnostic code and establishment of diagnostic guidelines, our understanding of this condition has grown. RECENT FINDINGS: FPIES affects patients from early infancy into adulthood. Any food can be a trigger, and common culprit foods vary geographically and by age. An understanding of the complex underlying immune mechanisms remains elusive, although studies show pan-leukocyte activation, cytokine release, and increased gastrointestinal permeability. Management involves trigger avoidance, and patients may benefit from the support of a dietitian to ensure adequate nutrient intake. Tolerance develops over time for most children, but due to the risk of severe symptoms, re-introduction of a suspected FPIES trigger is recommended only under supervision at an oral food challenge. Studies continue to evaluate the optimal challenge protocol. Caregivers of children with FPIES report high levels of anxiety and stress, which is attributed to the dramatic symptomatology, dietary restrictions, nutritional concerns, lack of confirmatory diagnostic tests, and limited tools for management of reactions. Our understanding of the FPIES diagnosis has improved over the last few decades, but there remain opportunities, particularly regarding discerning the pathophysiology and best management practices.

Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals

The rapid development and deployment of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has been questioned. Here we characterized SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during full BNT162b2 vaccination. Our results demonstrate that the second dose increases both the humoral and cellular immunity in naive individuals. On the contrary, the second BNT162b2 vaccine dose results in a reduction of cellular immunity in COVID-19 recovered individuals, which suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.

Immune Characterization of Bone Marrow-Derived Models of Mucosal and Connective Tissue Mast Cells

PURPOSE: It is well appreciated that mast cells (MCs) demonstrate tissue-specific imprinting, with different biochemical and functional properties between connective tissue MCs (CTMCs) and mucosal MCs (MMCs). Although in vitro systems have been developed to model these different subsets, there has been limited investigation into the functional characteristics of the 2 major MC subsets. Here, we report the immunologic characterization of 2 MCs subsets developed in vitro from bone marrow progenitors modeling MMCs and CTMCs. METHODS: We grew bone marrow for 4 weeks in the presence of transforming growth factor (TGF)-β, interleukin (IL)-9, IL-3, and stem cell factor (SCF) to generate MMCs, and IL-4, IL-3, and SCF to generate CTMCs. RESULTS: CTMCs and MMCs differed in growth rate and protease content, but their immune characteristics were remarkably similar. Both subsets responded to immunoglobulin E (IgE)-mediated activation with signaling, degranulation, and inflammatory cytokine release, although differences between subsets were noted in IL-10. CTMCs and MMCs showed a similar toll-like receptor (TLR) expression profile, dominated by expression of TLR4, TLR6, or both subsets were responsive to lipopolysaccharide (LPS), but not poly(I:C). CTMCs and MMCs express receptors for IL-33 and thymic stromal lymphopoietin (TSLP), and respond to these cytokines alone or with modified activation in response to IgE cross-linking. CONCLUSIONS: The results of this paper show the immunologic characterization of bone marrow-derived MMCs and CTMCs, providing useful protocols for in vitro modeling of MC subsets.