Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA): A summary report

Article (PDF Available)inThe Journal of allergy and clinical immunology 126(6):1119-28.e12 · December 2010with343 Reads
DOI: 10.1016/j.jaci.2010.10.011 · Source: PubMed
The 2nd Milan Meeting on Adverse Reactions to Bovine Proteins was the venue for the presentation of the first consensus-based approach to the management of cow's milk allergy. It was also the first time that the Grading of Recommendations, Assessments, Development, and Evaluation approach for formulating guidelines and recommendations was applied to the field of food allergy. In this report we present the contributions in allergen science, epidemiology, natural history, evidence-based diagnosis, and therapy synthesized in the World Allergy Organization Diagnosis and Rationale for Action against Cow's Milk Allergy guidelines and presented during the meeting. A consensus emerged between discussants that cow's milk allergy management should reflect not only basic research but also a newer and better appraisal of the literature in the light of the values and preferences shared by patients and their caregivers in partnership. In the field of diagnosis, atopy patch testing and microarray technology have not yet evolved for use outside the research setting. With foreseeable breakthroughs (eg, immunotherapy and molecular diagnosis) in the offing, the step ahead in leadership can only stem from a worldwide organization implementing consensus-based clinical practice guidelines to diffuse and share clinical knowledge.

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Available from: Motohiro Ebisawa
    • "Cow's milk allergy (CMA) is the most common type of IgE-mediated food allergy in young children, affecting around 2.5% of children below the age of 3 years [12,13]. Cow's milk contains around 20 proteins able to induce IgE-mediated allergy [14], of which 10 are reported in the official Allergen Nomenclature Database from the World Health Organization and International Union of Immunological Societies (WHO/IUIS) (www.allergen.org). β-lactoglobulin (BLG) officially designated Bos d 5, α-lactalbumin (ALA) officially designated Bos d 4 and caseins, officially designated Bos d 8, are the most important and major cow's milk allergens [15]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Characterisation of the specific antibody response, including the epitope binding pattern, is an essential task for understanding the molecular mechanisms of food allergy. Examination of antibody formation in a controlled environment requires animal models. The purpose of this study was to examine the amount and types of antibodies raised against three cow’s milk allergens; β-lactoglobulin (BLG), α-lactalbumin (ALA) and β-casein upon oral or intraperitoneal (i.p.) administration. A special focus was given to the relative amount of antibodies raised against linear versus conformational epitopes. Methods Specific antibodies were raised in Brown Norway (BN) rats. BN rats were dosed either (1) i.p. with the purified native cow’s milk allergens or (2) orally with skimmed milk powder (SMP) alone or together with gluten, without the use of adjuvants. The allergens were denatured by reduction and alkylation, resulting in unfolding of the primary structure and a consequential loss of conformational epitopes. The specific IgG1 and IgE responses were analysed against both the native and denatured form of the three cow’s milk allergens, thus allowing examination of the relative amount of linear versus conformational epitopes. Results The inherent capacity to induce specific IgG1 and IgE antibodies were rather similar upon i.p. administration for the three cow’s milk allergens, with BLG = ALA > β-casein. Larger differences were found between the allergens upon oral administration, with BLG > ALA > β-casein. Co-administration of SMP and gluten had a great impact on the specific antibody response, resulting in a significant reduced amount of antibodies. Together results indicated that most antibodies were raised against conformational epitopes irrespectively of the administration route, though the relative proportions between linear and conformational epitopes differed remarkably between the allergens. Conclusions This study showed that the three-dimensional (3D) structure has a significant impact on the antibodies raised for both systemic and orally administered allergens. A remarkable difference in the antibody binding patterns against linear and conformational epitope was seen between the allergens, indicating that the structural characteristics of proteins may heavily affect the induced antibody response.
    Full-text · Article · Aug 2014
    • "There are 3 types of inflammatory mechanisms that can mediate CMA: the " acute onset " immunoglobulin E-(IgE-) mediated, the " delayed onset " non-IgE cell-mediated, and the mixed typemediated allergies. Onset and clinical manifestations of CMA are varied among these clusters [1], hence complicating its "
    [Show abstract] [Hide abstract] ABSTRACT: Food allergy is an aberrant immune-mediated reaction against harmless food substances, such as cow's milk proteins. Due to its very early introduction, cow's milk allergy is one of the earliest and most common food allergies. For this reason cow's milk allergy can be recognized as one of the first indications of an aberrant inflammatory response in early life. Classically, cow's milk allergy, as is true for most other allergies as well, is primarily associated with abnormal humoral immune responses, that is, elevation of specific immunoglobulin E levels. There is growing evidence indicating that cellular components of both innate and adaptive immunity play significant roles during the pathogenesis of cow's milk allergy. This is true for the initiation of the allergic phenotype (stimulation and skewing towards sensitization), development and outgrowth of the allergic disease. This review discusses findings pertaining to roles of cellular immunity in allergic inflammation, and tolerance induction against cow's milk proteins. In addition, a possible interaction between immune mechanisms underlying cow's milk allergy and other types of inflammation (infections and noncommunicable diseases) is discussed.
    Full-text · Article · Jun 2014
    • "In this study the majority of children (53.4%) received an amino acid formula, which reflects the severity of patients seen within our tertiary centre. At the time of data collection, there were no UK-specific guidelines on formula choices for specific gastrointestinal conditions and the guidelines by the World Allergy Foundation had not been published [32]. A significant number of children according to parental reporting continued to require a dietary exclusion at 8 years of age. "
    [Show abstract] [Hide abstract] ABSTRACT: Food protein induced gastrointestinal allergies are difficult to characterise due to the delayed nature of this allergy and absence of simple diagnostic tests. Diagnosis is based on an allergy focused history which can be challenging and often yields ambiguous results. We therefore set out to describe a group of children with this delayed type allergy, to provide an overview on typical profile, symptoms and management strategies. This retrospective analysis was performed at Great Ormond Street Children's Hospital. Medical notes were included from 2002 -- 2009 where a documented medical diagnosis of food protein induced gastrointestinal allergies was confirmed by an elimination diet with resolution of symptoms, followed by reintroduction with reoccurrence of symptoms. Age of onset of symptoms, diagnosis, current elimination diets and food elimination at time of diagnosis and co-morbidities were collected and parents were phoned again at the time of data collection to ascertain current allergy status. Data from 437 children were analysis. The majority (67.7%) of children had an atopic family history and 41.5% had atopic dermatitis at an early age. The most common diagnosis included, non-IgE mediated gastrointestinal food allergy (n = 189) and allergic enterocolitis (n = 154) with symptoms of: vomiting (57.8%), back-arching and screaming (50%), constipation (44.6%), diarrhoea (81%), abdominal pain (89.9%), abdominal bloating (73.9%) and rectal bleeding (38.5%). The majority of patients were initially managed with a milk, soy, egg and wheat free diet (41.7%). At a median age of 8 years, 24.7% of children still required to eliminate some of the food allergens. This large retrospective study on children with food induced gastrointestinal allergies highlights the variety of symptoms and treatment modalities used in these children. However, further prospective studies are required in this area of food allergy.
    Full-text · Article · Aug 2013
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