Allergic responses induced by goat milk αS1-casein in a murine model of gastrointestinal atopy

Up to 3% of young children develop milk allergy and this may influence the development of immune-mediated diseases in later life. One protein that has been associated with allergic reactions to ruminant milk is α(S1)-casein (CN). Studies suggest that goat milk with low levels of α(S1)-CN may reduce allergenicity of milk, but the dose response to α(S1)-CN has not been confirmed. In this study, we examined the immune response to varying levels of goat α(S1)-CN in a mouse model of gastrointestinal allergy. BALB/c mice (aged 5 wk) were given intraperitoneal injections with α(S1)-CN and aluminum as adjuvant at 1 and 3 wk to sensitize mice to the antigen. In wk 5, groups of fasting mice (n=8/group) were challenged 4 times on alternate days by intragastric gavage with saline or 2, 10, or 20mg of α(S1)-CN. Serum levels of specific IgE, IgG(1), and IgG(2a) antibodies and mouse mast cell protease-I were determined. Interleukin-4, IL-10, and IFN-γ responses to 48-h activation with antigen were measured in cultured splenocytes. We determined that mice sensitized with α(S1)-CN had higher titers of specific IgG(1) and IgE antibodies compared with controls; however, groups challenged with differing doses of α(S1)-CN did not differ. The group challenged with the highest dose of α(S1)-CN had a 10-fold increase in mouse mast cell protease-I compared with the group challenged with saline. Both IL-4 and IL-10 were produced in a dose-dependent manner by cultured splenocytes incubated with α(S1)-CN. Overall, α(S1)-CN stimulated the production of cytokines associated with allergic disease in a dose-dependent manner. Thus, milk with lower levels of α(S1)-CN should contribute to a lesser antigenic burden.     

融合型原肌球蛋白MBP-CTB-TM构建及其口服致敏性评价

将麦芽糖结合蛋白（maltose-binding protein,MBP）、霍乱毒素B亚基（cholera toxin B subunit,CTB）以及增强型绿色荧光蛋白（enhanced green fluorescent protein,EGFP）基因重组构建MBP-CTB-EGFP并原核表达纯化,利用HEK293T细胞模型探究MBP-CTB-EGFP穿透细胞膜的能力,从而开发新型黏膜佐剂。进一步地,利用原肌球蛋白（tropomyosin,TM）重组融合蛋白MBP-CTB-TM,将其应用于Balb/c小鼠致敏实验,探究融合蛋白的致敏性及其对小鼠食物过敏相关免疫反应的影响,以达到降低过敏原剂量提高建模效率的效果。结果表明：MBP-CTB-EGFP具有作为黏膜佐剂的能力,从而促进外源蛋白进入HEK293T细胞内,且与转染方式相比,携带外源蛋白进入细胞的效率更高。另一方面,利用融合蛋白MBP-CTB-TM免疫小鼠,TM特异性IgE的OD450 nm达到0.4,而天然TM致敏组仅为0.05,此外融合蛋白致敏还导致高水平的TM特异性IgG1、IgG2a产生。本研究表明,融合蛋白MBP-CTB-TM致敏效果更好,有可能达到降低过敏原用量的效果,为后续食物过敏研究提供了有力工具。     

Allergenic and immunogenic potential of cow's milk β-lactoglobulin and caseins evidenced without adjuvant in germ-free mice

Scope: In most animal models of allergy, the development of an IgE response requires the use of an adjuvant. Germ‐free (GF) mice exhibit Th2‐polarized antibody responses combined with defective immunosuppressive mechanisms. The sensitizing potential of milk proteins was investigated in GF mice in the absence of adjuvant. Methods and results: β‐lactoglobulin (BLG) and whole casein (CAS) allergenicity was evaluated by means of intraperitoneal injections without adjuvant. Injections of BLG induced significant IgE and IgG1 responses in GF mice, while CAS injections provoked the production of IgG1 toward κ‐ and αS1‐caseins. No significant antibody response was evidenced in conventional (CV) mice. After in vitro BLG‐reactivation, IL‐4, IL‐5, IL‐13 and IFN‐γ productions by splenocytes were higher in GF mice than in CV mice. Heat‐treatment decreased BLG allergenicity as indicated by the absence of IgE production in GF mice. However, heat‐treatment increased protein immunogenicity and led to the production of anti‐BLG and anti‐κ‐casein IgG1 in both GF and CV mice. This correlated with enhanced productions of IL‐4, IL‐5 and IL‐13 in BLG‐reactivated splenocytes from CV mice. Conclusion: Gut colonization by commensal bacteria appeared then to significantly reduce the susceptibility of mice toward the intrinsic allergenic and immunogenic potential of milk proteins.     

对虾原肌球蛋白不同致敏途径对BALB/c小鼠致敏性的影响

随着食物过敏现象的日益普遍,其已成为工业化国家一个严重的公众健康问题。食物蛋白致敏机理的相关 研究大多借助于两大类小鼠模型,即口服致敏模型和局部或皮肤致敏模型。然而,不同模型之间的差异以及如何选 择合适的模型进行研究却鲜有人关注。鉴于此,本研究旨在通过比较对虾原肌球蛋白口服灌胃和腹腔注射两种给药 途径对BALB/c小鼠致敏性的影响,寻求最佳给药方式,以便建立有效的动物模型,并在分子及免疫水平研究其致 敏机理,从而为食物过敏原动物模型的构建提供一定的理论依据,也为研究食物过敏原致敏机制以及预防治疗食物 过敏提供重要的模型依据。结果表明,腹腔注射小鼠血清中特异性免疫球蛋白（immunoglobulin,Ig）E、组胺以及 辅助性T细胞（helper T cells,Th）2型细胞因子含量均高于口服灌胃小鼠,其致敏性更好。此外,口服灌胃小鼠血 清特异性IgG2a、干扰素-γ、调节性T细胞水平增加,表明虽有黏膜佐剂作用,但口服给药仍可能使小鼠产生口服免 疫耐受,从而降低对虾原肌球蛋白对其的致敏性。本研究表明,腹腔注射原肌球蛋白比口服灌胃更易使小鼠致敏, 其Th1/Th2平衡被打破,Th2反应占据优势,更适合用于构建食物致敏动物模型。     

Germin-like protein Cit s 1 and profilin Cit s 2 are major allergens in orange (Citrus sinensis) fruits

Oranges are clinically relevant allergenic foods. To date, orange allergens have not been characterized in detail. The study is aimed at analyzing the sensitization profile in orange-sensitized subjects with and without clinical allergy, and to identify orange allergens. Fifty-six sensitized subjects with self-reported reactions to orange were grouped into reactors (anaphylaxis or multiple episodes of immediate reactions and/or positive challenge tests) and non-reactors (negative open food challenge tests). Allergens were characterized by IgE immunoblotting, N-terminal sequencing, IgE-inhibition assays, and mediator release assays were performed to determine the allergenic potency of orange profilin. Of 56 subjects, 23 were classified as orange allergic showing mainly an oral allergy syndrome. Of 23 subjects classified as orange allergic, 22 were sensitized to profilin, Cit s 2. In patients with mono-sensitization to profilin in vitro histamine releases up to 75% from basophils were induced using orange extract and purified plant profilins. Of the allergic patients 78% were sensitized to germin-like protein, Cit s 1. Both allergens showed retained IgE reactivity in heat-processed orange juice. Interestingly, subjects with and without clinical allergy showed a comparable sensitization profile. Profilin and germin-like proteins are major orange allergens. The potential clinical relevance of orange profilin was indicated by its strong capacity to release histamine from basophils. However, a predominant sensitization to both allergens in subjects without symptoms also indicates a high frequency of clinically insignificant sensitization.     

The anti‐allergenic properties of milk kefir and soymilk kefir and their beneficial effects on the intestinal microflora

Food allergy is now recognized as a worldwide problem, and like other atopic disorders its incidence appears to be increasing. Kefir is reported to possess the ability to reduce intestinal permeation of food antigens; however, no experimental study has clearly evaluated the relationships between kefir consumption, allergen‐specific IgE response, and intestinal microflora. The aim of this study was to evaluate the effect of oral consumption of milk kefir and soymilk kefir on in vivo IgE and IgG1 production induced by ovalbumin (OVA) in mice. The effects of kefir administration on the murine intestinal microflora were also examined. Oral administration of milk kefir and soymilk kefir for 28 days significantly increased the fecal populations of bifidobacteria and lactobacilli, while it significantly decreased those of Clostridium perfringens. Milk kefir and soymilk kefir also significantly decreased the serum OVA‐specific IgE and IgG1 levels for both groups, but not those of the IgG2a analogues. Consumption of milk kefir and soymilk kefir suppressed the IgE and IgG1 responses and altered the intestinal microflora in our supplemented group, suggesting that milk kefir and soymilk kefir may be considered among the more promising food components in terms of preventing food allergy and enhancement of mucosal resistance to gastrointestinal pathogen infection. Copyright © 2006 Society of Chemical Industry     

主要坚果类过敏原致敏机理的初步探讨

本文以坚果过敏蛋白为抗原,构建小鼠动物致敏免疫模型,探讨坚果过敏原的致敏机理,为坚果类食物安全评价和安全开发提供有效的实验依据。选取六种坚果为原料,以昆明小鼠为受试小鼠,坚果蛋白液以0.01 mg/g进行灌胃致敏,第33 d和34 d以0.02 mg/g激发致敏,通过测定小鼠血清IgE、IgG、腹腔肥大细胞及类胰蛋白酶和血象指标,研究其病理特征。结果表明,致敏激发后小鼠IgE与IgG最高水平为0.91和0.93,组胺释放率阳性组为58%,中剂量组为40%,高剂量组为55%;小鼠腹腔肥大细胞体外激发后脱颗粒高剂量组最多以及类胰蛋白酶活性也最高;中和高剂量组、阳性组白细胞数较高(9.7±6.1、9.6±2.4、9.2±2)×109/L,低剂量组、中剂量组和高剂量组的血小板数依次降低。说明致敏后小鼠凝血功能显著减弱,免疫系统受到侵袭,体内诱发产生IgE抗体,并启动过敏介质的释放机制,导致过敏反应Ⅰ型变态反应的发生。     

Goats' milk of defective alpha(s1)-casein genotype decreases intestinal and systemic sensitization to beta-lactoglobulin in guinea pigs

Contradictory results have been reported on the use of goats' milk in cows' milk allergy. In this study the hypothesis was tested, using a guinea pig model of cows' milk allergy, that these discrepancies could be due to the high genetic polymorphism of goats' milk proteins. Forty guinea pigs were fed over a 20 d period with pelleted diets containing one of the following: soyabean proteins (group S), cows' milk proteins (group CM), goats' milk proteins with high (group GM1) or low (group GM2) alpha(s1)-casein content. Parenteral sensitization to GM1 and GM2 proteins as also assessed. The sensitization was measured (1) by systemic IgG1 antibodies directed against bovine or caprine beta-lactoglobulin (beta-lg), alpha-lactalbumin (alpha-la) and whole caseins, and (2) by intestinal anaphylaxis measured in vitro in Ussing chambers, by the rise in short-circuit current (delta Isc) in response to milk proteins. Guinea pigs fed on CM and GM1 developed high titres (> 1500) of anti-beta-lg IgG1, with an important cross reactivity between goat and cow beta-lg. However, in guinea pigs fed on GM2, anti-goat beta-lg IgG1 antibodies were significantly decreased compared with GM1 guinea pigs (mean IgG1 titres were 546 and 2046 respectively), and the intestinal anaphylaxis was significantly decreased (3.5+/-4.5 microA/cm2) compared with that observed in GM1 guinea pigs (8.3+/-7.6 microA/cm2). Animals receiving GM1 or GM2 proteins via the parenteral route developed a marked sensitization. These results suggest that the discrepancies observed in the use of goats milk in cows' milk allergy could be due, at least in part, to the high genetic polymorphism of goats' milk proteins.     

Comparison of the immunogenicity of yak milk and cow milk

This is a comparison of potential allergenicity in a mouse model. Balb/C mice were sensitized by intraperitoneal injections (administered in three doses) of skimmed milk, casein, and whey protein from cow or yak milk. After 4 weeks, the mice were challenged and killed, sera were collected, and the spleens removed for analysis. An enzyme-linked immunosorbent assay was used to determine the specific antibodies (IgG and IgE) and cytokine. The number of mice with diarrhea was higher in the cow milk protein-sensitized group than in the yak milk protein-sensitized group. Serum (IgG, IgE) antibodies and histamine levels were also higher in cow milk protein-sensitized mice. Cytokine production by spleen-derived T cells showed high levels of interleukin-4 and interleukin-5 production and low levels of interferon-γ in cow milk protein and yak milk protein-sensitized mice. Lymphocyte proliferation ratio induced by yak milk protein was lower than cow milk protein. All results indicated that Maiwa yak milk protein may less allergenic than cow milk protein in mice.     

Immunogenic and allergenic potentials of natural and recombinant innocuous proteins

A new aspect of protein immunogenic and allergenic properties has become important recently, when there is a higher chance that our immune system will be exposed to novel protein antigens and/or familiar protein antigens with an unprecedented high frequency and large amount. These proteins are innocuous, nontoxic, and noninvasive by themselves, and include various natural proteins from the environment and recombinant proteins from industry. The technical term allergenic has been used for such proteins and their abilities to induce specific IgE production and to cross-link IgE/Fc epsilonRI on the surface of mast cells and basophiles have been recognized. As for the environmental proteins, some physicochemical properties (solubility, stability, and permeability across a mucosal epithelium) of the proteins indirectly play important roles in their allergenic potential because they do not originate from invasive pathogens as vehicles. Indeed, several lines of experimental evidences have been accumulated indicating that all proteins are absorbed across mucosal epithelia by transcellular transport and/or through interstitial spaces among the epithelial cells but not at equal levels. Some animal models have been established for natural sensitization to some allergenic proteins by feeding or intragastric administration without an adjuvant and, in a few cases, some symptoms resembling human allergy and even anaphylaxis have been induced by oral challenge with the proteins. Sometimes, even to self-proteins, the immunogenic or allergenic potential is given by post-translational modifications and possibly by unknown structural/conformational alterations, when they are exogenous self-proteins, such as recombinant human proteins for drug use. Despite the accumulation of knowledge and the progress in analytical technology on protein allergenicity, it is still crucial to predict the allergenic potential of novel and unused proteins. However, some animal models are applicable for assessing the relative allergenic potential of processed proteins in comparison with that of native proteins in preclinical studies.     

Partially hydrolyzed whey proteins prevent clinical symptoms in a cow's milk allergy mouse model and enhance regulatory T and B cell frequencies

1 Scope

Partially hydrolyzed cow's milk proteins are used to prevent cow's milk allergy in children. Here we studied the immunomodulatory mechanisms of partial cow's milk hydrolysates in vivo.

2 Methods and results

Mice were sensitized with whey or partially hydrolyzed whey using cholera toxin. Whey‐specific IgE levels were measured to determine sensitization and immune cell populations from spleen, mesenteric lymph nodes and Peyer's patches after oral whey administration were measured by flowcytometry. Whey‐specific IgE and IgG1 levels in partial whey hydrolysate sensitized animals were enhanced, but challenge did not induce clinical symptoms. This immunomodulatory effect of partial whey hydrolysate was associated with increased regulatory B and T cells in the spleen, together with a prevention of IgM‐IgA class switching in the mesenteric lymph nodes and an increased Th1 and activated Th17 in the Peyer's patches.

3 Conclusion

Partial hydrolysate sensitization did not induce whey‐induced clinical symptoms, even though sensitization was established. Increased regulatory cell populations in the systemic immune system and a prevention of increased total Th1 and activated Th17 in the intestinal immune organs could contribute to the suppression of allergic symptoms. This knowledge is important for a better understanding of the beneficial effects of hydrolysates.     

Oral inoculation with Gymnorhynchus gigas induces anti-parasite anapyhylactic antibody production in both mice and rats and adverse reactions in challenge mice

This study was performed to mimic human consumption of fish flesh infected with larvae of the fish cestode Gymnorhynchis gigas and examine possible side effects thereof. Both a rat and a mouse G. gigas oral inoculation model were used. The rat model was evaluated according to propensity to induce stress responses in three tissues and anaphylactic antibody production. The mouse model measured anti-G. gigas IgG, M and A (H + L) levels in intestinal fluids, fecal suspensions and serum and specific serum IgE levels by enzyme-linked immunosorbent assay. Additionally, biological activity of anaphylactic antibodies in test mice and rats were evaluated utilizing challenge reinoculation(s) and intradermal skin testing, respectively. With the rat inoculation model, we noted both occurrence of a shock response, viz. increased expression of heat shock proteins in intestine and spleen, and of immediate-type skin reactions. No positive wheals were seen on skin sites treated with PBS or soluble Trichinella spiralis extract. With the mouse model, our results showed that all body fluids tested had significantly more anti-G. gigas IgG, M and A (H + L) than their counterparts from either PBS-treated or T. spiralis-infected controls. In addition, the mouse G. gigas model had significantly higher specific serum IgE. When challenged by oral route all test mice (n = 5) manifested immediate-type signs of distress. Repeated exposure to the "allergen", produced clinical signs appearing more rapidly and persisting longer. These findings suggest that feeding on fish infected with G. gigas plerocercoids triggers the production of anaphylactic-type antibodies in both rats and mice and, by implication, possibly also in humans.     

对虾原肌球蛋白致敏小鼠模型的构建及乳酸菌肠黏膜免疫效应对致敏性的影响

以原肌球蛋白（tropomyosin,TM）为主要过敏原,腹腔注射6 周龄BALB/c雌、雄小鼠,从第14天开始给治疗组小鼠口服灌胃长双歧杆菌婴儿亚种（Bifidobacterium longum subsp.）1.2202或芽孢乳酸菌09.712（Bacillus coagulans 09.712）,连续灌胃20 d。根据小鼠腹泻情况、过敏症状评分、血清中组胺（histamine,HIS）质量浓度、TM特异性免疫球蛋白（immunoglobulin,Ig）E水平变化构建TM致敏及益生菌治疗小鼠模型;通过氯乙酸萘酚酯酶染色、高碘酸希夫试剂特殊染色法检测各组小鼠肠道部位的肥大细胞和杯状细胞,通过免疫组化法检测各组小鼠肠道部位的CD4＋ T细胞和嗜酸性粒细胞;探究肠黏膜免疫在TM致敏及益生菌缓解TM致敏作用中的机理。结果表明：雌性小鼠更适用于构建TM致敏模型;益生菌灌胃可以通过降低血清中HIS质量浓度和IgE水平缓解肠黏膜免疫反应,减轻TM过敏症状。本研究从肠黏膜免疫反应角度探究了其在TM致敏中的作用,为食物过敏的研究提供参考。     

Effects of enzymatic hydrolysis on the allergenicity of natural cow milk based on a BALB/c mouse model

Cow milk allergy is one of the most prevalent food allergies worldwide, particularly in infants and children. To the best of our knowledge, minimal research exists concerning the antigenicity of cow milk (CM). This study was performed to evaluate the allergenicity of enzymatically hydrolyzed cow milk (HM) in a BALB/c mouse model. The mice were randomly divided into 5 groups (n = 12/group), which were sensitized with phosphate-buffered saline, CM, and HM (Alcalase-, or Protamex-, or Flavorzyme-treated cow milk; Novo Nordisk; AT, PT, FT, respectively), respectively, using cholera toxin as adjuvant on d 0, 7, 14, 21. On d 28, the test mice were orally challenged with phosphate-buffered saline, CM, and HM (AT, PT, or FT) alone. Anaphylactic symptoms were monitored in the mice. Antibody, cytokine, histamine, and mouse mast cell protease-1 (mMCP-1) levels were measured using enzyme-linked immunosorbent assays. In addition, the numbers of T helper (Th)1 and Th2 cells, as well as the proportions of CD4⁺CD25⁺Foxp3⁺ Treg cells, in mouse spleens were detected using flow cytometry. Statistical significance was determined by one-way ANOVA. The results revealed significant differences between CM- and HM-challenged mice. Among these, the clinical scores of HM-challenged mice (AT, 1.50; PT, 2.00; FT, 1.92) were lower than those of CM-challenged mice (positive control, 2.83), but body weight and temperature of HM-challenged mice were higher than those of CM-challenged mice. In addition, significant reductions of allergen-specific IgE, IgG, histamine, and mMCP-1 were showed in HM-challenged mice, especially for histamine, ranging from 171.42 ng/mL to 214.94 ng/mL. Remarkable reductions of IL-4, IL-5, and IL-13 levels, as well as elevations of interferon-γ and IL-10 levels in the spleens of HM-challenged mice were also detected. Moreover, the number of Th2 cells decreased in the HM-challenged mice, to 2.36% (AT), 1.79% (PT), and 4.03% (FT), respectively, whereas the numbers of Th1 cells (AT, 6.30%; PT, 6.70%; FT, 6.56%) and the proportions of CD4⁺CD25⁺Foxp3⁺Tregs (AT, 8.86%; PT, 9.21%; FT, 9.16%) increased significantly. Our findings indicate that exposure to HM was sufficient to induce a shift toward a Th1 response, thereby reducing potential allergenicity. Importantly, these results will lay a theoretical foundation for the development of hypoallergenic CM products.     

Maternal peanut consumption provides protection in offspring against peanut sensitization that is further enhanced when co-administered with bacterial mucosal adjuvant

The aims of the present study were to assess whether protection against peanut (PN) sensitization can be conferred by maternal PN consumption alone and if so, whether protection was increased by mucosal adjuvant co-administration. Mice were fed with low dose of either PN or PN with cholera toxin (CT) preconceptionally, and during pregnancy and lactation. Offspring serum PN-specific immunoglobulins and cellular responses by splenocytes and mesenteric lymph node (MLN) cells were determined after an active PN sensitization protocol. Milk was collected from lactating mothers of 11-21-day-old pups for evaluation of PN-specific immunoglobulin levels. We found that offspring of PN fed mothers exhibited lower PN-specific IgE levels and reduced PN-stimulated splenocyte and MLN cells cytokine secretion than offspring of non PN fed mothers. CT co-administration with PN enhanced these responses.. Milk from mothers fed PN and CT, but not PN alone preconceptionally and during pregnancy and lactation contained markedly and significantly increased levels of both peanut-specific IgG2a and IgA. Our study demonstrated that maternal feeding of PN alone had a protective effect against PN sensitization of the progeny, which was enhanced by co-administration of a mucosal adjuvant. Increased levels of PN-specific IgG2a and/or IgA in milk were seen when PN and CT were administered together, suggesting that transmission of maternal immunoglobulins may play a role in the observed protection.     

Pepsin treatment of whey proteins under high pressure produces hypoallergenic hydrolysates

BALB/c mice were used to assess the ability of a whey protein hydrolysate obtained by pepsin treatment under high pressure (400 MPa, 37 °C, 30 min, HWP), to induce anaphylaxis, antibody production and cytokine responses in comparison with the whey protein isolate (WP) from which it is derived. HWP did not contain intact allergens and 50% of its peptides ranged between 10 and 3 kDa. Challenge with HWP did not induce clinical signs, body temperature changes or release of mast cell proteinase-1 in mice sensitized to WP. Immunization of mice with HWP did not produce WP-specific antibodies or allergic reactions upon HWP or WP challenge and thus, it can be considered hypoallergenic. However, HWP stimulated Th2 responses in splenocytes from sensitized mice. These characteristics make HWP a good candidate to be used in the management of milk allergy in diagnosed patients or to induce tolerance to whey proteins.Industrial relevanceHydrolysis with pepsin under high pressure produces in minutes a whey protein hydrolysate that complies with the health claims of the European guidelines on infant and follow-on formulas related to the reduction of risk to allergy to milk proteins. This process constitutes an alternative to the exhaustive enzymatic hydrolysis treatments used in the processing of hypoallergenic formulas that release short peptides and free amino acids to adversely affect organoleptic properties and technological value.     

Evaluation of allergenicity of cow milk treated with enzymatic hydrolysis through a mouse model of allergy

Cow milk (CM) allergy is a worldwide concern. Currently, few studies have been performed on the immunoreactivity of CM and fewer still on the antigenicity of CM in vivo and in vitro. In this study, we assessed the potential allergenicity of enzymatically hydrolyzed CM using in vitro ELISA and oral sensitization and challenge of BALB/c mice. Alcalase-, Protamex-, and Flavourzyme-treated CM (all from Novozymes) diminished IgE binding capacity, with greatest reductions of 56.31%, 50.62%, and 56.45%, respectively. Allergic symptoms and levels of total IgG₁ were reduced, and allergic inflammation of the lung, jejunum, and spleen was relieved. Moreover, the numbers of CD8⁺ T and B220⁺ cells decreased, and the balance of CD4⁺ T/CD8⁺ T cells was effectively regulated. These findings suggest that the potential allergenicity of CM was reduced by enzymatic hydrolysis, and our research will lay a solid foundation for developing high-quality hypoallergenic CM products.     

The balance between caseins and whey proteins in cow's milk determines its allergenicity

Cow's milk allergy is quite common in the first years of human life. Protein composition plays an important role in this pathology, particularly the casein/whey protein ratio. It is known that milks from different species have different sensitization capacities although their protein sources are quite similar. Thus, the objective of this work was to compare the allergenicity of native cow's milk and milk with a modified ratio of casein and whey proteins in a murine model of atopy. Twenty-four Balb/c mice were orally sensitized to native cow's milk or modified cow's milk with a casein/whey protein ratio of 40:60. During the sensitization period, the number of mice suffering from diarrhea was significantly higher in the native cow's milk-sensitized group than in the modified milk-sensitized group. Once mice were killed, plasma histamine levels were shown to be significantly higher in native cow's milk-sensitized mice. In addition, cow's milk proteins induced a higher lymphocyte sensitization in the native milk-sensitized mice, with a significant increase in the specific proliferation ratio of these cells.These results suggest that the balance between caseins and whey proteins plays an important role in the sensitization capacity of cow's milk, and its modification might be a way to reduce the allergenicity of cow's milk.