Search PubMed⌕ Search

Biomedical subjects

Robert E Esch

Publications and source records attributed to Robert E Esch.

6 recordsLinked to original sources

Evaluation of allergen vaccine potency.

The development of reliable and clinically relevant potency assays is essential to the practice of safe and effective allergen-specific immunotherapy. Allergen standardization in the United States is based on the establishment of a national reference assigned with a biological potency unit to which manufacturers' products are compared using validated relative potency assays. This ensures, at least with standardized allergen vaccines, comparability between lots used in clinical practice. Recent progress in the ability to measure the specific allergen content of allergen vaccines has led to its application in monitoring consistency and characterizing allergen preparations. More recently, the "major allergen" content of allergen vaccines has become a means to compare extracts from different manufacturers and to recommend immunotherapy dosing regimens. At the same time, qualitative differences exist between manufacturers' products, and most allergen vaccines used in clinical practice are nonstandardized. Therefore, this approach can be confusing and is misleading. The establishment of additional allergen reference standards and the development of reliable, accurate, and clinically relevant potency assays are urgently needed.

Allergens↗

Allergens.

What makes an antigen an allergen? This question has been at the core of much research regarding the basic mechanisms of allergy as well as the development of diagnostic and therapeutic allergen products. Great strides have been made since Kjell Aas asked this question in his classic review in Allergy (1), but we appear no closer to the answer. The mechanisms leading to allergic reactions have been well described in recent years and our understanding of it at the molecular level has greatly improved. Conversely, the molecular structures responsible for these allergic reactions are not as well understood. Techniques for the isolation, identification, and epitope mapping of allergens have greatly enhanced our ability to test old and new ideas about what makes an antigen an allergen. We continue to search for "major allergens," and when we identify them, we hope to delineate "allergenic determinants" and "immunodominant epitopes." Even now, unique structural motifs or determinants responsible for allergenicity have not yet been identified, and we will probably never find them.

Allergens↗

Manufacturing and standardizing fungal allergen products.

The importance of fungal allergen products in the practice of clinical allergy is frequently underestimated. A wide variety of fungal species have been demonstrated to elicit allergic symptoms and to sensitize patients. The quality of fungal allergen preparations might have a significant effect on the specificity and sensitivity of diagnostic tests. Varying degrees of cross-reactivity have been shown among fungal genera, and the clinical relevance of this cross-reactivity has been neither fully appreciated nor applied to clinical practice. In addition, an increasing number of potentially new fungal allergen sources for which commercial extracts are not available are being identified. Manufacturers of allergen products have the formidable task of providing quality fungal allergen extracts that are routinely used for specific allergy diagnosis and treatment in the clinic. Currently there are no standardized fungal allergen products available in the United States because of inherent difficulties with manufacturing and standardizing fungal extracts. Without intervention, progress will not be forthcoming.

Allergens↗

Major allergen measurements: sources of variability, validation, quality assurance, and utility for laboratories, manufacturers, and clinics.

The isolation and characterization of prominent allergenic proteins or glycoproteins is an important step in the development of allergenic extracts exhibiting improved definition, consistency, and clinical utility. Quantitative analyses specific for major allergenic components currently are being performed in numerous corporate and academic laboratories but have not been validated within or across laboratories in a systematic manner. In our laboratory, validation of double-bind (sandwich) ELISA assays for a diverse group of major allergens or extract components revealed a number of critical assay variables and reagent incubation conditions that directly influenced the precision, accuracy, specificity, and robustness of these tests. Data from ELISA methods for six allergens (Dermatophagoides farinae Der f 1, Alternaria Alt a 1, dog albumin, dog Can f 1, fire ant Sol i 3, and yellow jacket venom Ves 5) showed that up to twofold differences in results were observed when analysts or microplates were varied. Analyses of dog allergens using multiple reagents and concentrations indicated that twofold variations in results also can be produced by distinct combinations of materials or incubations from different assay steps. Data from Can f 1 and egg white analyses produced up to fivefold differences in antigen concentrations based on changes in the capture antibody source (mouse monoclonal versus rabbit polyclonal) or storage buffer. These results suggest that differences in major allergen concentrations reported by different testing laboratories may be related to assay differences as well as extract variations and raise questions as to the accuracy of major allergen concentrations and therapeutic dose recommendations reported at regional and national allergy meetings. Validated double-bind ELISA methods may be well suited for consistency monitoring and standardization of extracts provided that reference materials, reagent qualifications, and interlaboratory comparability are defined precisely.

Allergens↗