Antigen-specific T-cell responses in patients with non–IgE-mediated gastrointestinal food allergy are predominantly skewed to TH2

Morita, Hideaki; Nomura, Ichiro; Orihara, Kanami; Yoshida, Koichi; Akasawa, Akira; Tachimoto, Hiroshi; Ohtsuka, Yoshikazu; Namai, Yoshiyuki; Futamura, Masaki; Shoda, Tetsuo; Matsuda, Akio; Kamemura, Norio; Kido, Hiroshi; Takahashi, Tsuyoshi; Ohya, Yukihiro; Saito, Hirohisa; Matsumoto, Kenji

doi:10.1016/j.jaci.2012.09.005

Cited by 92 publications

(65 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3 PBMCs from patients with non–IgE-mediated cow’s milk allergy show increased TNF-α production compared with PBMCs from patients with outgrown cow’s milk allergy, 12 but it is not clear if the patients described in that cohort would fit diagnostic criteria of FPIES. Patients with FPIES have also been described to have a T H 2-skewed cytokine profile from antigen-restimulated PBMCs, 13 consistent with our recent findings. 11 It is difficult to reconcile a T H 2-skewed T-cell profile as underlying such a distinct clinical entity as FPIES.…”

supporting

confidence: 92%

Systemic innate immune activation in food protein–induced enterocolitis syndrome

Goswami¹,

Blázquez²,

Kosoy

et al. 2017

Journal of Allergy and Clinical Immunology

103

View full text Add to dashboard Cite

Background Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated food allergy of infancy whose pathophysiology is poorly understood. Objectives We set out to identify and phenotype allergen-responsive cells in peripheral blood of a cohort of subjects undergoing supervised food challenge for FPIES. Methods: We profiled antigen-responsive cells in PBMCs by flow cytometry, and examined cells in whole blood obtained before and after challenge by CyTOF mass cytometry and RNAseq. Results Using a CD154-based detection approach, we observed that milk, soy, or rice-responsive T cells, and TNF-α–producing CD154+ T cells, were significantly lower in those with outgrown FPIES compared with those with active FPIES. However, levels were within the normal range and were inconsistent with a role in the pathophysiology of FPIES. Profiling of whole blood by CyTOF demonstrated profound activation of cells of the innate immune system after food challenge, including monocytes, neutrophils, natural killer cells, and eosinophils. Activation was not observed in children with outgrown FPIES. We confirmed this pattern of innate immune activation in a larger cohort by RNAseq. Furthermore, we observed pan–T-cell activation and redistribution from the circulation after a positive food challenge but not in those who had outgrown their FPIES. Conclusions Our data demonstrate a compelling role of systemic innate immune activation in adverse reactions elicited by foods in FPIES. Further investigation is needed to identify the mechanism of antigen specificity of adverse reactions to foods in FPIES.

show abstract

supporting

confidence: 92%

Systemic innate immune activation in food protein–induced enterocolitis syndrome

Goswami¹,

Blázquez²,

Kosoy

et al. 2017

Journal of Allergy and Clinical Immunology

103

View full text Add to dashboard Cite

show abstract

“…This finding suggests that TNF-α may be implicated in the pathogenesis of eosinophilic colitis in infants and children with FPIAP, possibly by altering the intestinal barrier capacity. In line with our observations, a recent study examining T cell responses to milk protein, TNF-α concentrations in the culture supernatants of milk protein-stimulated peripheral blood mononuclear cells from patients with gastrointestinal food allergies were significantly greater than those seen in patients with IgE-mediated cow's milk allergy or control subjects [41]. …”

Section: Discussionsupporting

confidence: 89%

Food Protein-Induced Non-Immunoglobulin E-Mediated Allergic Colitis in Infants and Older Children: What Cytokines Are Involved?

Ozen

Gülcan²,

Ercan

et al. 2015

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: Food protein-induced allergic proctocolitis (FPIAP) is mostly a non-immunoglobulin E-mediated disease where a T-cell-mediated reaction to cow's milk protein has been suggested. We determined the expression of transforming growth factor (TGF)-β, TGF-β receptor-1, tumor necrosis factor (TNF)-α, CD86, and CD23 on the colon mucosa to investigate their roles in the pathogenesis of the two subtypes of FPIAP, i.e. infantile FPIAP and FPIAP in older children. Methods: Group 1 comprised children with infantile FPIAP (age <6 months, n = 21), group 2 referred to FPIAP in older children (age >1.5 years, n = 7), and group 3 included children with juvenile hyperplastic polyps (n = 22). Immunohistochemical staining of colonic biopsy specimens was performed. Results: The expression of TNF-α was signiﬁcantly higher in groups 1 and 2 compared to group 3. Group 2 patients had a signiﬁcantly lower TGF-β expression compared to the other groups. The expression of CD86 was higher in group 1 than in group 3 (p = 0.012). Eosinophil counts per high-power field in the lamina propria were signiﬁcantly correlated with CD86 expression (p = 0.026, r = 0.388). Conclusion: Our results suggest that TNF-α is implicated in the pathogenesis of both types of FPIAP. The decreased activity of TGF-β receptor-1 accompanied by the increased expression of CD86 in infants and the decreased activity of TGF-β in older children appear to play a role in the development of FPIAP.

show abstract

“…A systemic increase in circulating TNFα during acute FPIES reactions has not been described. Morita et al recently published a comprehensive analysis of T cell cytokine responses in 65 children with non-IgE-mediated milk allergies (comprised of a mix of patients with symptoms consistent with FPIES, food protein induced enteropathy, and food protein induced proctocolitis) 43 . Patients were compared to control subjects and those with IgE-mediated allergy to milk.…”

Section: Introductionmentioning

confidence: 99%

Immunopathophysiology of food protein–induced enterocolitis syndrome

Berin

2015

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

There is increasing recognition of the non-IgE-mediated gastrointestinal food allergy known as food protein-induced enterocolitis syndrome (FPIES), with several recent publications summarizing the clinical experience with FPIES in the US, the UK, Europe, and Australia. Our understanding of the mechanisms linking food exposure to typical symptoms of vomiting, hypotension, and diarrhea has lagged far behind our understanding of the immune mechanisms of IgE-mediated food allergy. The goal of this overview is to summarize and critique the current state of knowledge of the immunology of FPIES, and to identify major gaps in our knowledge that need to be addressed in order to make significant gains in developing therapies and prevention strategies for FPIES.

show abstract

Antigen-specific T-cell responses in patients with non–IgE-mediated gastrointestinal food allergy are predominantly skewed to TH2

Cited by 92 publications

References 5 publications

Systemic innate immune activation in food protein–induced enterocolitis syndrome

Systemic innate immune activation in food protein–induced enterocolitis syndrome

Food Protein-Induced Non-Immunoglobulin E-Mediated Allergic Colitis in Infants and Older Children: What Cytokines Are Involved?

Immunopathophysiology of food protein–induced enterocolitis syndrome

Contact Info

Product

Resources

About