A robust method for the estimation and visualization of IgE cross-reactivity likelihood between allergens belonging to the same protein family

Abstract

Among the vast number of identified protein families, allergens emanate from relatively few families which translates to only a small fraction of identified protein families. In allergy diagnostics and immunotherapy, interactions between immunoglobulin E and allergens are crucial because the formation of an allergen-antibody complex is necessary for triggering an allergic reaction. In allergic diseases, there is a phenomenon known as cross-reactivity. Cross-reactivity describes a situation where an individual has produced antibodies against a particular allergenic protein, but said antibodies fail to discriminate between the original sensitizer and other similar proteins that usually belong to the same family. To expound the concept of cross-reactivity, this study examines ten protein families that include allergens selected specifically for the analysis of cross-reactivity. The selected allergen families had at least 13 representative proteins, overall folds that differ significantly between families, and include relevant allergens with various potencies. The selected allergens were analyzed using information on sequence similarities and identities between members of the families as well as reports on clinically relevant cross-reactivities. Based on our analysis, we propose to introduce a new A-RISC index (Allergens’–Relative Identity, Similarity and Cross-reactivity) which describes homology between two allergens belonging to the same protein family and is used to predict the likelihood of cross-reactivity between them. Information on sequence similarities and identities, as well as on the values of the proposed A-RISC index is used to introduce four categories describing a risk of a cross-reactive reaction, namely: high, medium-high, medium-low and low. The proposed approach can facilitate analysis in component-resolved allergy diagnostics, generation of avoidance guidelines for allergic individuals, and help with the design of immunotherapy.

Allergens and their associated small molecule ligands—their dual role in sensitization

“…Serum albumins (SAs) are members of a highly conserved protein family that includes numerous allergens. 31 , 32 , 33 SAs are clinically relevant allergens that originate from animals, where they are major blood components. SAs are also present in milk, muscle, and epithelia.…”

Structural Characterization of Act c 10.0101 and Pun g 1.0101—Allergens from the Non-Specific Lipid Transfer Protein Family

“…A-RISC values were calculated as described previously [ 82 ]. Multiple sequence alignments of proteins belonging to the nsLTP family were performed with Clustal Omega [ 78 ].…”

Mapping B-Cell Epitopes for Nonspecific Lipid Transfer Proteins of Legumes Consumed in India and Identification of Critical Residues Responsible for IgE Binding

“…Tri a 14 and Pur p 3 both are LTPs and belong to the same family of proteins; however, they share < 50% identity, and account for reduced cross-reactivity among the B-cell epitopes. Although, there are recent advancements in the research protocols employed for evaluating cross reactivity among proteins, nonetheless sequence-homology based studies for evaluating clinically relevant cross-reactivity, still remains relevant and authentic [54]. Till date several studies, and significant amount of clinical data has already validated the antigenic dominance of peach LTPs among other LTP allergens [49].…”