Persistent Cow's Milk Research Articles

Quoi de neuf en allergologie pédiatrique en 2004 ? Partie 3 : allergie cutanée, alimentaire, médicamenteuse et aux venins d'insectes (Une revue de la littérature internationale d'octobre 2003 à septembre 2004)

Severity and risk of persistence/relapse of atopic dermatitis are correlated with total IgE levels and food sensitization. Weaning to hypoallergenic formula improves SCORAD and gut barrier function in breastfed infants with persistent atopic dermatitis. Risk of anaphylaxis is high in children with cold-induced urticaria, and these children should be provided with an epinephrine autoinjector. Occult sensitizations are important risk factors for food allergy. The predictive values of serum egg-specific IgE levels are debated. The diagnostic value of atopy patch-tests with foods is confirmed in children with non-immediate food hypersensitivity reactions. Risk of persistence of food allergy is high in children with high specific IgE levels and/or with a low rate of decrease in food-specific IgE levels. Oral desensitization induces tolerance in children with persistent cow's milk allergy, except for children with very high levels of specific IgE. However, tolerance to anaphylactogenic food may be temporary, with the occurence of severe relapses after a few months. Ten per cent of children treated with penicillins are sensitized to these antibiotics. However, only a few of these children are at risk of developing allergy to penicillins. Non allergic hypersensitivity to non steroidal anti-inflammatory drugs is frequent in children. Sublingual immunotherapy may be efficient in children with latex hypersensitivity. A clinically important number of non-hyposensitized children do not outgrow hymenoptera venom allergy. In contrast, venom immunotherapy leads to a significantly lower risk of systemic reaction to stings. Thus, children with moderate to severe allergic reactions to hymenoptera stings should receive specific immunotherapy.

Transient vs persistent cow's milk allergy and development of other allergic diseases

Transient <i>vs</i> persistent cow's milk allergy and development of other allergic diseases

Cow's milk?specific T-cell reactivity of children with and without persistent cow's milk allergy: Key role for IL-10

BackgroundThe role of antigen-specific T cells in the mechanism of food allergy or maintenance of tolerance toward an innocuous antigen, such as cow's milk, is not yet fully understood.ObjectiveThe cow's milk–specific T-cell response of donors with various allergic backgrounds was investigated.MethodsCow's milk–specific T-cell clones (TCCs) were generated from the blood of children with persistent cow's milk allergy (CMA) and the blood of cow's milk–tolerant allergic and nonallergic control subjects. The TCCs were characterized by their antigen-specific proliferation, cytokine production, and activation status.ResultsCow's milk–specific TCCs of children with persistent CMA were TH2 skewed, and the production of IL-4 and IL-13 was significantly correlated with the expression of the activation marker CD25. TCCs of the allergic control subjects were characterized by a high production of IL-10, which was positively correlated with the production of IL-4 and IFN-γ and with the expression of CD25. TCCs derived from nonallergic control subjects had an attenuated response toward cow's milk in that they did not produce high levels of cytokines nor did they express high levels of surface markers. As in the allergic control subjects, in the nonallergic control subjects IL-10 production was positively correlated with the expression of CD25.ConclusionThe activation status of T cells derived from persistent donors with CMA was associated with the production of IL-4 and IL-13, whereas activated TCCs of cow's milk–tolerant control subjects were characterized by the production of IL-10 and, to a lesser extent, IFN-γ. These findings suggest that activated CD4+ T cells (characterized by a high CD25 expression) might contribute to the tolerogenic immune response toward an antigen, such as cow's milk, through the production of IL-10.

Cow's milk–specific T-cell reactivity of children with and without persistent cow's milk allergy: Key role for IL-10

Background The role of antigen-specific T cells in the mechanism of food allergy or maintenance of tolerance toward an innocuous antigen, such as cow's milk, is not yet fully understood. Objective The cow's milk–specific T-cell response of donors with various allergic backgrounds was investigated. Methods Cow's milk–specific T-cell clones (TCCs) were generated from the blood of children with persistent cow's milk allergy (CMA) and the blood of cow's milk–tolerant allergic and nonallergic control subjects. The TCCs were characterized by their antigen-specific proliferation, cytokine production, and activation status. Results Cow's milk–specific TCCs of children with persistent CMA were T H2 skewed, and the production of IL-4 and IL-13 was significantly correlated with the expression of the activation marker CD25. TCCs of the allergic control subjects were characterized by a high production of IL-10, which was positively correlated with the production of IL-4 and IFN-γ and with the expression of CD25. TCCs derived from nonallergic control subjects had an attenuated response toward cow's milk in that they did not produce high levels of cytokines nor did they express high levels of surface markers. As in the allergic control subjects, in the nonallergic control subjects IL-10 production was positively correlated with the expression of CD25. Conclusion The activation status of T cells derived from persistent donors with CMA was associated with the production of IL-4 and IL-13, whereas activated TCCs of cow's milk–tolerant control subjects were characterized by the production of IL-10 and, to a lesser extent, IFN-γ. These findings suggest that activated CD4 + T cells (characterized by a high CD25 expression) might contribute to the tolerogenic immune response toward an antigen, such as cow's milk, through the production of IL-10.

IgE-binding peptides coupled to a commercial system as diagnostic instrument for persistent cow's milk allergy

Rationale Using SPOTs-membrane technology, we recently identified IgE-binding epitopes recognized mainly by patients with persistent cow's milk allergy [CMA]. The present study was performed to confirm the relevance of these “informative” epitopes in a larger study population using peptide-coupled ImmunoCAPs and the Pharmacia-UniCAP-System. Methods 74 patients with challenge-proven CMA were included in the study. Twenty-nine patients subsequently outgrew their allergy, 15 of those at a median-age of 3 years [range 1-4 years, group-A] and 14 at a median-age of 8 years [range 6-18 years, group-B]. The remaining 45 children retained their allergy until a median-age of 8 years [range 5-22 years, group-C]. Five peptides, representing the “informative” IgE-binding epitopes were coupled to the ImmunoCAPs. Banked sera obtained at the time of clinical reactivity were used for analyses. Median milk-specific IgE levels were 1.9 kU/l [range 0.5->100 kU/l], 3.5 kU/l [range 0.9->100 kU/l] and 29.1 kU/l [range 0.5->100 kU/l] for group-A, -B and -C, respectively. Results Patients with persistent CMA [ group-C] had significantly higher levels of peptide-specific IgE [median 2.8 kU/l, range <0.35-36.7 kU/l] than children who subsequently outgrew their allergy at three or eight years of age [ group-A: median <0.35 kU/l, range <0.35-0.5 kU/l, p<0.001 and group B: median <0.35 kU/l, range <0.35-6.4 kU/l, p<0.05]. Conclusions Our study confirmed that the presence of IgE antibodies to distinct allergenic epitopes of cow' milk proteins can be used as a marker of persistent CMA. Moreover, linking these peptides to a commercial matrix should enable the conduct of large prospective studies and simplify future diagnostic approaches.

Cow's milk-specific T cell reactivity of children with and without persistent cow's milk allergy; key role for IL-10

Rationale The role of antigen-specific T-cells in the mechanism of food allergy or maintenance of tolerance towards an innocuous antigen such as cow's milk is not yet fully understood. Methods To investigate the cow's milk-specific T-cell response of donors with various allergic backgrounds, T-cell clones were generated and their antigen-specific proliferation, cytokine production and activation status was determined. Results Cow's milk-specific T-cell clones of children with persistent cow's milk allergy are Th2 skewed compared to the T-cell clones of cow's milk-tolerant allergic and non-allergic controls. In the cow's milk-allergic patients the production of IL-4, IL-13 is significantly correlated with the expression of the activation marker CD25. T-cell clones of the allergic control subjects are characterized by a high production of IL-10, which is positively correlated with the production of IL-4 and IFN-γ and with the expression of CD25. T-cell clones derived from non-allergic control subjects do not produce high levels of cytokines nor express high levels of surface markers. As in the allergic controls, also in the non-allergic controls, IL-10 production was positively correlated with the expression of CD25. Conclusions The activation status of T-cells derived from persistent cow's milk-allergic donors is associated with the production of IL-4 and IL-13 whereas activated T-cell clones of cow's milk-tolerant control subjects are characterized by the production of IL-10 and to a lesser extent IFN-γ. These findings suggest that activated CD4 + T-cells (characterized by a high CD25 expression) may contribute to the tolerogenic immune response towards an antigen, such as cow's milk via the production of IL-10.

B-cell epitopes as a screening instrument for persistent cow's milk allergy.

Cow's milk is one of the most common causes of food allergy in the first years of life. We recently defined IgE-binding epitopes of all 6 major cow's milk proteins (alpha(s1)-, alpha(s2)-, beta-, and kappa-casein; alpha-lactalbumin; and beta-lactoglobulin) and had some evidence suggesting that IgE antibodies from patients with persistent cow's milk allergy (CMA) recognize different epitopes on cow's milk proteins than do those from patients who were likely to outgrow their allergy. In this study we sought to assess whether recognition of IgE antibodies of certain epitopes of cow's milk proteins would clearly separate the patients with life-long CMA from those who will become clinically tolerant to cow's milk. According to the known IgE-binding regions of cow's milk proteins, 25 decapeptides of alpha(s1)-casein, alpha(s2)-casein, kappa-casein, alpha-lactalbumin, and beta-lactoglobulin, comprising the core epitopes, were synthesized on a cellulose-derivatized membrane. Sera from 10 patients with persistent CMA and 10 patients who subsequently outgrew their milk allergy were used to investigate the differences in epitope recognition. Five IgE-binding epitopes (2 on alpha(s1)-casein, 1 on alpha(s2)-casein, and 2 on kappa-casein) were not recognized by any of the patients with transient CMA but showed binding by the majority of the patients with persistent allergy. The presence of IgE antibodies against at least 1 of 3 epitopes (amino acid [AA] 123-132 on alpha(s1)-casein, AA 171-180 on alpha(s2)-casein, and AA 155-164 on kappa-casein) identified all patients with persistent CMA. The presence of IgE antibodies to distinct allergenic epitopes of cow's milk proteins can be used as a marker of persistent CMA. Prospective studies are needed to investigate the usefulness of these informative epitopes in predicting life-long CMA in young children.

Recognition of IgE binding regions of bovine αS2-casein differs in patients with persistent and transient cow's milk allergy

Recognition of IgE binding regions of bovine αS2-casein differs in patients with persistent and transient cow's milk allergy

Persistent cow's milk protein intolerance in infants: the changing faces of the same disease.

Recent research has shown that cow's milk protein intolerance (CMPI) often persists beyond 4 years of age. To evaluate the clinical and immunological characteristics of a group of infants with persistent CMPI. Twelve infants (6 m, 6f) with persistent CMPI were followed up from birth until a median age of 5 years. The patients underwent CMP challenge each year to evaluate CMP-tolerance. As controls we followed 26 infants (12 m, 14 f) with CMPI that resolved within 1-2 years. A family history of atopic disease was found in 10/12 patients with persistent CMPI and in 10/26 controls (P<0.01). Clinical presentation changed over time: at onset symptoms were prevalently gastrointestinal, while at the end of the study there was an increased frequency of wheezing and constipation and a higher frequency of delayed reactions to CMP-challenge than at study commencement (9/12 vs 2/12; P<0.007). 11/12 infants with persistent CMPI and 3/26 controls (P<0.0001) presented multiple food intolerance. During the observation period 9/12 infants with persistent CMPI and 2/26 controls showed atopic disease: asthma, rhinitis, eczema (P < 0.0001). Persistent CMPI forms are characterized by: (a) considerable importance of familial atopic disease; (b) change in CMPI manifestations over time and more prolonged delay between CMP consumption and manifestation of symptoms; (c) very high frequency of multiple food intolerance and allergic diseases.

Cow's milk intolerance presenting as necrotizing enterocolitis: E. de Peyer and J. Walker-Smith. Helv Paediatr Acta 32:509–515, 1977

Case history is reported of an infant who was changed from breast to bottle feeding at fourth day of life, who on ninth day developed bilious vomiting and bloody diarrhoea. Later gas was found in colonic wall on X-ray. Necrotizing enterocolitis was diagnosed and infant managed with total intravenous alimentation. On recovery although she tolerated breast milk, return to cow's milk formula lead to return of bloody diarrhoea. Subsequently she thrived on a cow's milk-free diet based on chicken meat formula. At four months after total of 15 ml cow's milk she had an acute anaphylactic reaction. She recovered and is well on milk-free diet. Thus, this infant has recovered from necrotizing enterocolitis but has evidence of persistent cow's milk protein intolerance. The hypothesis is put forward that in this child cow's milk protein played a major role in the pathogenesis of necrotizing enterocolitis.