Allergenicity prediction by protein sequence

Stadler, Michael; Stadler, Beda M.

doi:10.1096/fj.02-1052fje

Cited by 198 publications

(172 citation statements)

References 26 publications

(29 reference statements)

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“…In the normal case the single allergens will constitute a minor component of the extract compared to the non allergenic proteins, because only a minority of the proteins are able to induce a switch to IgE production [17]. These extracts are subject to batch-to-batch variation due to different reasons like extraction procedure used, biochemical stability of the allergens, protease content, and storage [18].…”

Section: Problems Related To Allergen Extracts and Mould Extracts In mentioning

confidence: 99%

Specific IgE Testing (RAST)

Crameri¹

2009

Aspergillosis: From Diagnosis to Prevention

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The diagnosis of allergic diseases is based on a combination of clinical history, physical examination, in vivo challenges, and in vitro test methods for the detection of allergen-specific IgE antibodies in the serum of patients. In spite of the fact that the determination of allergen-specific IgE in serum is widely used in daily clinical practice, one should be aware that such determinations, although useful for routine screening of possible allergies, are not sufficient to diagnose the disease. Clinical history and provocation tests should always be considered to confirm an allergy indicated by elevated allergen-specific IgE levels in serum. This specially applies to the diagnosis of mould allergy in general, and of Aspergillus fumigatusrelated allergic complications in particular.

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Section: Problems Related To Allergen Extracts and Mould Extracts In mentioning

confidence: 99%

Specific IgE Testing (RAST)

Crameri¹

2009

Aspergillosis: From Diagnosis to Prevention

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“…The presence of cross-reactive structures like enolase and MnSOD, which are also described as latex allergens [16,17], cyclophilin known as a birch pollen allergen [53], thioredoxin described as a prominent food allergen [54], and serine proteases which play an important role in house dust mite allergy [55] indicate that the whole repertoire of allergenic molecules is highly redundant and, thus, limited to a discrete number of structures [56]. In contrast to polysensitisation which is easy to demonstrate by simple determination of the RAST values against different allergen extracts [8], cross-reactivity between fungal extracts is a poorly investigated phenomenon which, however, could contribute to a better understanding of polysensitisation.…”

Section: Cross-and Autoreactivitymentioning

confidence: 99%

Overview of Aspergillus Allergens

Crameri¹,

Glaser²,

Vilhelmsson

et al. 2009

Aspergillosis: From Diagnosis to Prevention

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Fungi in general and, Aspergillus fumigatus (A. fumigatus) in particular, are able to produce complex patterns of IgE-binding molecules. Robotics-based high throughput screening of A. fumigatus cDNA libraries displayed on phage surfaces revealed at last 81 different sequences encoding structures potentially able to bind to serum IgE of sensitised individuals suffering from A. fumigatus-related complications. Although not all of these allergens have been characterised in detail, A. fumigatus still represents the best investigated allergenic source. A total of 23 A. fumigatus allergens are recorded by the official allergen list of the International Union of Immunological Societies ( www.allergen.org ) and this is by far the longest allergen list reported for a single allergenic source. The IgE-binding molecules include species-specific as well as phylogenetically highly conserved cross-reactive structures and such with unknown function. A subset of cDNAs have been used to produce and characterise the corresponding recombinant allergens which have proven to be useful diagnostic reagents allowing specific detection of A. fumigatus sensitisation and differential diagnosis of allergic bronchopulmonary aspergillosis. Structures highly conserved through different species like manganese-dependent superoxide dismutase, P 2 acidic ribosomal protein, cyclophilins and thioredoxins induce, beyond sensitisation, IgE antibodies able to cross-react with the corresponding homologous self-antigens. The frequently observed cross-reactivity is traceable back to shared discontinuous B-cell epitopes as shown by detailed analyses of the crystal structures.

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“…The practice of searching for identical short amino acid matches between the introduced GE protein and sequences from known allergens had not been evaluated in terms of efficiency until recently [9,10]. However, short peptide sequence matches have been used to evaluate most, if not all, of the proteins introduced into commercially available GE crops that have been reviewed by US, Japan and EU regulators.…”

Section: Short Contiguous Amino Acid Matchesmentioning

confidence: 99%

“…There are various programs and approaches that could be used to evaluate the 3-D structure of a protein, given the primary structure [10,11,21]. The size, hydrophobicity, polarity, and charge of the side-groups of each amino acid contributes to the 3-D structure.…”

Section: Structural Comparisonsmentioning

confidence: 99%

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Practical and predictive bioinformatics methods for the identification of potentially cross‐reactive protein matches

Goodman

2006

Molecular Nutrition Food Res

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A bioinformatics comparison of proteins introduced into food crops through genetic engineering provides a mechanism to identify those proteins that may present an increased risk of allergic reactions for individuals with existing allergies. The goal is to identify proteins that are known to be allergens or are so similar to an allergen that they may induce allergic cross‐reactions. Three comparative approaches have traditionally been used, or considered for safety evaluations. One identifies any short (6–8) amino acid segment of the protein that exactly matches a known allergen sequence. The second is an overall primary sequence comparison using Basic Local Alignment Search Tool (BLAST) or FASTA to find matches of greater than 35% identity over 80 amino acids. The third is based on 3‐D prediction programs to identify 3‐D similarities that might predict potential cross‐reactivity. The utility of each of these approaches was debated in the bioinformatics workshop. The consensus agreement from the expert workshop participants was that the short‐segment match (e. g., 6–8 amino acids) provides an unacceptably high rate of false positive matches and an uncertain rate of true positive matches, and was not particularly useful for an allergenicity evaluation performed in the context of comprehensive safety evaluation. There was no consensus regarding the most appropriate bioinformatics method, an acceptable scoring criteria for triggering closer examination subsequent to a positive match, or an acceptable scoring mechanism for ranking the utility of the various 3‐D approaches that were discussed during the workshop. However, the general consensus was that the most practical approach at this time is to evaluate primary sequence identities to known allergens using either FASTA or BLAST. While there was good agreement that identities of greater than 35% over 80 or more amino acids (recommended by Codex in 2003) is quite conservative, the conclusion was that additional data or studies would be needed to justify changing this criterion as there is some evidence that some individuals sensitized to proteins in evolutionarily conserved protein families may experience cross‐reactions to proteins sharing approximately 40% identity.

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Allergenicity prediction by protein sequence

Cited by 198 publications

References 26 publications

Specific IgE Testing (RAST)

Specific IgE Testing (RAST)

Overview of Aspergillus Allergens

Practical and predictive bioinformatics methods for the identification of potentially cross‐reactive protein matches

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