Open Access

Research Article

Hazard Identification: Immediate Needs Top

Research needed to improve hazard identification fell into three categories: development of animal models, identification and characterization of food allergens, and establishment of well-defined clinical serum banks. All were deemed important to improve the Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO) decision tree (FAO/WHO 2001) or to replace it with a better approach. Also discussed was the need to improve human skin test technology for incorporation in a decision tree. Animal models are needed that could be used not only for hazard identification purposes but also to determine relative potency, to derive sensitization and elicitation thresholds, and to define the conditions under which tolerance (failure to develop an allergic response to potential food allergens) is induced. Identification, characterization, purification, and banking of food allergens (and nonallergens) are needed for two reasons: to provide positive (and negative) controls for animal and serum bank tests and for use in defining the characteristics that confer on food proteins the ability to induce allergic sensitization, that is, to establish structure-activity relationships. Serum from clinically well-defined allergic individuals needs to be banked for use in screening proteins of unknown allergenicity. Development of proteomic approaches to screen potential allergens (specific IgE on a chip) was also suggested as a research need. Characterization of allergens and development of serum banks require a systematic process for recording adverse events and obtaining informed consent for use of serum obtained in epidemiologic and experimental studies. Once developed, all tests for hazard identification will require standardization and validation--no small task. These research needs are summarized in Table 1.

Table 1.

Basic Mechanistic Research Top

Appropriate animal models (not necessarily the same as those used for hazard identification) and human clinical and epidemiologic studies are needed to assess the correlation between antigen-specific IgE and clinical disease and to investigate the influence of the route, duration, and nature of exposure on the development of sensitization. An important research need is to investigate the mechanisms underlying food allergy, including the development of and failure to develop oral tolerance, and identification of possible windows of vulnerability during immune development (including in utero and during lactation) or unique exposure conditions that might place children at greater risk. The mechanisms underlying the development of tolerance to ingested antigens, whether by passive (anergy) or active (suppressor cells) processes, are poorly understood and may be crucial to understanding what makes a protein allergenic and what makes an individual susceptible. The contributions of in utero exposure, gut immaturity, and exposure via breast milk to children's risk of sensitization also need to be determined. Studies (possibly using transgenic mice) are needed to assess the heritable factors that contribute to susceptibility to food allergy. Epidemiology is needed to determine whether the incidence of food allergy in the industrialized world, like the incidence of other types of allergic disease, is increasing.

The natural history of non-IgE-mediated food allergies (although somewhat beyond the scope of this current workshop) was also considered an important long-term research need. Questions were raised as to whether certain foods were associated with this type of allergy and whether IgE is a reasonable surrogate marker in this instance or if other biomarkers would be more appropriate. The context in which food is presented, including the matrix, concomitant infections, and other sources of gut inflammation, also deserves further attention with respect to both IgE- and non-IgE-mediated food allergies. Basic mechanistic research needs are summarized in Table 1.

Recommendations Top

In summary, there was consensus that research should progress quickly in the area of hazard identification to improve or replace the FAO/WHO decision tree. Support was particularly strong for the development, standardization, and validation of appropriate animal model(s) for this purpose. It was also generally agreed that there is much we do not know about the development of food allergies, and that more basic research in this area would help us to control the risks more effectively and efficiently. More work is needed than any one funding organization is likely to be able to support. Therefore, it is recommended that there be significant coordination between these organizations and an integrated approach to tackling this problem. Open and free exchange of information as it becomes available is needed to facilitate these research endeavors.

References Top

1. FAO/WHO. 2001. Evaluation of Allergenicity of Genetically Modified Foods. Report of a Joint FAO/WHO Expert Consultation of Allergenicity of Foods Derived from Biotechnology, 22-25 January 2001, Rome, Italy. Available: http://www.fao.org/es/esn/gm/allergygm.p​df [accessed 11 September 2002].
2. Germolec DR, Kimber I, Goldman L, Selgrade MJK. 2003. Key issues for the assessment of the allergenic potential of genetically modified foods: breakout group reports. Environ Health Perspect 111:1131–1139. Find this article online