Guidelines for using pollen cross-reactivity in formulating allergen immunotherapy.

There is a trend among allergen extract companies to diminish the number of individual extracts available for commercial use. This is driven in part by economic considerations and in part by constraints imposed by the US Food and Drug Administration. As much as 2/3 of previously manufactured extracts are or will no longer be available. In this setting, knowledge of pollen allergen interrelationships and cross-reactivity is crucial for formulation of inhalant allergen immunotherapy. In addition, as optimal doses for major allergens become clarified, cross-reactivity considerations should also affect formulation. Adverse reactions because of overdosing can occur if cross-reactivity is ignored. Plant systematic (taxonomy) is becoming more precise. The taxonomy of Judd et al is supported by morphologic, embryologic, and palynologic evidence, as well as analysis of biochemical, chloroplast gene, chromosome, and DNA data. Cloning of recombinant allergens has identified homologous proteins and clarified functions. It has been suggested that protein family content, or molecular classification, rather than botanical taxonomy is a superior way to address cross-reactivity issues. However, as has been shown with profilins and major grass allergens, even a high degree of amino acid homology does not always mean strong cross-reactivity. Two premises govern cross-reactivity inferred by plant systematics. The first is that accepted botanical taxonomy reflects phylogeny: that 2 plants in the same genus evolved from a common progenitor, and 2 in the same family or order did so from more distant ancestors. The second premise is that closely related plants will have a greater number of shared antigens than distantly related ones. This approach has been generally validated. The exception is there are many highly preserved proteins, even across plant, fungi, and animal kingdoms, that share cross-reactivity. Examples are profilins, lipid transfer proteins, and pathogenesisrelated proteins. The small differences that exist between these ubiquitous, presumably vital proteins explain why these are frequently, although not always, only minor allergens.