The time-course of milk antigen–induced TNF-α secretion differs according to the clinical symptoms in children with cow’s milk allergy

Benlounes, Nadia; Candalh, Céline; Matarazzo, P; Dupont, Christophe; Heyman, Martine

doi:10.1016/s0091-6749(99)70300-3

Cited by 80 publications

(57 citation statements)

References 37 publications

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“…The number of subjects with cow's milk allergy and healthy controls evaluated in this study was limited. However, our findings align with data from the literature suggesting that the use of TNF-α, IL-10, and IL-12 in PBMC cultures could have a predictive role for CMPA (2,20,21). This finding is in contrast with other studies that used similar models, which found low levels of TNF-α and interferon (32).…”

Section: Discussionsupporting

confidence: 89%

“…In particular, it has been suggested that interleukin (IL)-12 might play an important role in inhibiting inappropriate IgE synthesis and allergic inflammation as a result of allergen exposure (19). Furthermore, more recent reports have suggested that quantitation of cytokines, including tumor necrosis factor-α (TNF-α) and IL-10, in culture supernatants of cow's milk-stimulated PBMCs could be considered as a diagnostic or predictive test to identify cow's milk allergy among patients with immediate and non-immediate adverse reactions (2,20,21), and also helpful to reduce the need for food allergen challenges in young children (22).…”

Section: Introductionmentioning

confidence: 99%

“…In such a regard, some reports indicated that the measurement Our data showed that, PBMCs from subjects with CMPA stimulated in culture by cow's milk proteins, produced levels of TNF-α, IL-10, and IL-12 that were significantly higher than in PBMC's from non-allergic control subjects tested with the same protein fractions. Previous studies separately investigated the activity of various cytokines, including TNF-α, IL-10, and IL-12, suggesting their possible role in unveiling CMPA (2,20,21). However, none of the available diagnostic tests are able to conclusively prove or disprove whether a child has CMPA (3).…”

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confidence: 99%

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Levels of inflammatory cytokines from peripheral blood mononuclear cells of children with cow’s milk protein allergy

et al. 2018

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Aim: The aim of the study was to investigate the level of cytokines in cultures of cow's milk protein-stimulated peripheral blood mononuclear cells of patients with cow's milk protein allergy. Material and Methods:Eleven children with cow's milk protein allergy and 11 non-allergic controls were studied. Their peripheral blood mononuclear cells were cultured alone and in the presence of cow's milk α-lactalbumin; β-lactoglobulin; αS 1, αS 2, β, and κ-casein fraction mixtures; and a cow's protein mixture from whole milk. Production of cytokines, tumor necrosis factor-α, interleukin-10, and interleukin-12 were determined in culture supernatants.Results: In cow's milk protein-stimulated peripheral blood mononuclear cell cultures of children with cow's milk protein allergy, tumor necrosis factor-α, interleukin-10, and interleukin-12 production was significantly higher than in non-allergic controls (p<0.05). No difference in cytokine production was found between cultures obtained from unstimulated peripheral blood mononuclear cell cultures of both cow's milk protein allergy and non-allergic controls. Conclusions:The findings of this preliminary study align with data from the literature suggesting that the investigation of tumor necrosis factor-α, interleukin-10, and interleukin-12 in cow's milk protein-stimulated peripheral blood mononuclear cell cultures of children may be taken in further consideration to explore whether they might have a predictive role for cow's milk protein allergy. Further studies are therefore needed to extensively investigate this issue. Keywords: Challenge, cow milk, cytokines, immunoglobulin, interleukin, tumor necrosis factor Original Article IntroductionCow's milk protein allergy (CMPA) is an adverse immunologic response to cow's milk proteins (1). In particular, four casein fractions (αS 1, αS 2, β, and κ-casein) and two whey proteins (α-lactalbumin and β-lactoglobulin) are considered the most important allergenic proteins contained in cow's milk (2). Cow's milk protein allergy is one of the most common forms of food allergy in infants aged below 24 months in economically advanced countries (3) and its prevalence in this age group is estimated as 2-7.5%, whereas 5 to 15% of infants show symptoms suggesting adverse reactions to cow's milk components (4,5). Preventing the onset of inappropriate elimination diets in children with CMPA is important (4). In fact, the only effective treatment for CMPA is the total avoidance of cows' milk, which has to be replaced by appropriate substitutes (6), including soy formulas or casein, extensively hydrolyzed whey formulas or other mammalian milks such as goat's milk (7), which is frequently used although several studies raised concerns regarding its tolerability and safety, particularly in children (3,8,9).The immune reaction to cow's milk proteins is determined by immunoglobulin (Ig)-E or non-IgE-mediated type of response (10). Currently, the diagnosis relies both on IgE tests, such as the skin prick test, and measurement of serum-specific Ig...

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Levels of inflammatory cytokines from peripheral blood mononuclear cells of children with cow’s milk protein allergy

et al. 2018

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“…Higher baseline tryptase levels (although within normal range for age) were found in children with active CM-FPIES compared with those who had outgrown CM-FPIES, as documented by OFC; there was no change in tryptase after OFC Increased TNF-α and decreased expression of TGF-ß receptors, known to protect the intestinal barrier from the penetration of foreign antigen have been found in the intestinal mucosa of FPIES patients [97,100,110,111].…”

Section: Ip-10mentioning

confidence: 87%

Food Protein–Induced Enterocolitis Syndrome

Nowak‐Węgrzyn

Jarocka-Cyrta

Castro

2017

J Investig Allergol Clin Immunol

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Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-, cell-mediated food allergy of unknown prevalence and pathophysiology. Onset is typically during the first year of life; seafood-induced FPIES may start in adulthood. Acute FPIES manifests within 1-4 hours after ingestion with repetitive emesis, pallor, and lethargy progressing to dehydration and hypovolemic shock in 15% of cases. Chronic FPIES manifests with intermittent emesis, watery diarrhea, and poor growth progressing to dehydration and hypovolemic shock over a period of days to weeks. Chronic FPIES has been only reported in infants aged less than 3 months fed with cow milk (CM) or soy formula. The most common triggers are CM, soy, rice, and oat. Diagnosis of FPIES relies on recognition of a pattern of clinical symptoms and may be missed owing to the absence of typical allergic symptoms (eg, urticaria, wheezing) and delayed onset in relation to food ingestion. Physician-supervised food challenge is recommended if diagnosis or the trigger food is not clear and to evaluate for resolution. Testing for food-specific IgE is usually negative, although a subset of patients, usually with CM-induced FPIES may develop sensitization to foods. Such atypical FPIES tends to have a more prolonged course. Despite the potential severity of the reactions, no fatalities have been reported, and FPIES has a favorable prognosis. In most cases, FPIES resolves by age 3-5 years, although persistence of CM-induced FPIES and soy FPIES into adulthood has been reported. The first international consensus guidelines on diagnosis and management of FPIES were published in 2017. Given that the pathophysiology of FPIES is poorly understood, there are no diagnostic biomarkers and no therapies to accelerate resolution. These unmet needs warrant future investigations to improve the care of patients with FPIES. Key words: FPIES. Food protein-induced enterocolitis syndrome. Non-IgE-mediated food allergy. Food allergy. Cow milk allergy. ResumenSEIOA es una alergia alimentaria con patofisiología y prevalencia desconocidas, que típicamente comienza en el primer año de vida, mientras que la producida por pescado suelo tener su comienzo en adultos. La forma aguda se manifiesta entre la hora y 4 horas tras la ingesta del alimento con emesis, palidez, letargia progresiva por deshidratación y shock hipovolémico en el 15% de los casos. La forma crónica se manifiesta con emesis intermitente, diarreas y crecimiento pobre con progresión hacia la deshidratación y shock hipovolémico en un periodo de días o semanas. La forma crónica se ha podido observar únicamente en niños menores de 3 años alimentados con leche de vaca o fórmula de soja. Los desencadenantes más frecuentes son la leche de vaca, la soja, el arroz y avena. El diagnóstico es clínico y puede ser difícil debido a la ausencia de síntomas alérgicos típicos (urticaria, asma…) y a la relación retardada con la ingesta. Es recomendable la provocación controlada si el diagnóstico clínico o el alimento implicado no son claros y tamb...

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“…their particular frequency in young infants, in whom pathophysiological investigations remain difficult and ethically questionable, and the lack of animal models in particular. In infants with food protein-induced enterocolitis syndrome (FPIES), TNF-α secreted from peripheral blood mononuclear cells cultured with food proteins has been shown to be responsible for the reaction [12]. Duodenal biopsy specimens of affected infants have increased staining for TNF-α and decreased staining for the regulatory cytokine receptor TGF-β [13].…”

Section: Pathophysiologymentioning

confidence: 99%

Food Allergy: Recent Advances in Pathophysiology and Diagnosis

Dupont

2011

Ann Nutr Metab

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Approximately 5% of young children and 3–4% of adults exhibit adverse immune responses to foods in westernized countries, with a tendency to increase. The pathophysiology of food allergy (FA) relies on immune reactions triggered by epitopes, i.e. small amino-acid sequences able to bind to antibodies or cells. Some food allergens share specific physicochemical characteristics that allow them to resist digestion, thus enhancing allergenicity. These allergens encounter specialized dendritic cell populations in the gut, which leads to T-cell priming. In case of IgE-mediated allergy, this process triggers the production of allergen-specific IgE by B cells. Tissue-resident reactive cells, including mast cells, then bind IgE, and allergic reactions are elicited when these cells, with adjacent IgE molecules bound to their surface, are re-exposed to allergen. Allergic reactions occurring in the absence of detectable IgE are labeled non-IgE mediated. The abrogation of oral tolerance which leads to FA is likely favored by genetic disposition and environmental factors (e.g. increased hygiene or enhanced allergenicity of some foods). For an accurate diagnosis, complete medical history, laboratory tests and, in most cases, an oral food challenge are needed. Noticeably, the detection of food-specific IgE (sensitization) does not necessarily indicate clinical allergy. Novel diagnostic methods currently under study focus on the immune responses to specific food proteins or epitopes of specific proteins. Food-induced allergic reactions represent a large array of symptoms involving the skin and gastrointestinal and respiratory systems. They can be attributed to IgE-mediated and non-IgE-mediated (cellular) mechanisms and thus differ in their nature, severity and outcome. Outcome also differs according to allergens.

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The time-course of milk antigen–induced TNF-α secretion differs according to the clinical symptoms in children with cow’s milk allergy

Cited by 80 publications

References 37 publications

Levels of inflammatory cytokines from peripheral blood mononuclear cells of children with cow’s milk protein allergy

Levels of inflammatory cytokines from peripheral blood mononuclear cells of children with cow’s milk protein allergy

Food Protein–Induced Enterocolitis Syndrome

Food Allergy: Recent Advances in Pathophysiology and Diagnosis

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