Distinct transcriptome profiles differentiate nonsteroidal anti-inflammatory drug–dependent from nonsteroidal anti-inflammatory drug–independent food-induced anaphylaxis

• Published in: Journal of allergy and clinical immunology Vol. 137; no. 1; pp. 137 - 146
• Main Authors: Muñoz-Cano, Rosa, Pascal, Mariona, Bartra, Joan, Picado, Cesar, Valero, Antonio, Kim, Do-Kyun, Brooks, Stephen, Ombrello, Michael, Metcalfe, Dean D., Rivera, Juan, Olivera, Ana
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016; Elsevier Limited
• Subjects: Adult; Allergens - immunology; Allergy and Immunology; Anaphylaxis; Anaphylaxis - genetics; Anaphylaxis - immunology; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Antigens; Blood; Cancer; Carrier Proteins - immunology; Female; Food; Food allergies; food allergy; Food Hypersensitivity - genetics; Food Hypersensitivity - immunology; Gastrointestinal diseases; Gene expression; Genomes; Humans; Immunoglobulin G - immunology; Interferon-gamma - immunology; Kinases; lipid transfer protein syndrome; Male; Metabolism; Middle Aged; Neutrophils; Nonsteroidal anti-inflammatory drugs; Proteins; Receptor, Adenosine A3 - genetics; Receptors, IgG - genetics; Sequence Analysis, RNA; Transcriptome; transcriptome analysis; nonsteroidal anti-inflammatory drugs; lipid transfer protein syndrome; NSAID; RPKM; LTP; LTP-A; α-gal; food allergy; Pru p 3; HV; Anaphylaxis; RNA-Seq; ADORA3; SPT; ROS; NSAID-LTP-A; transcriptome analysis; IPA; Reactive oxygen species; Reads per kilobase of exon per million mapped reads; Peach lipid transfer protein; Adenosine receptor 3; RNA sequencing; Ingenuity Pathway Analysis; Skin prick test; NSAID-related LTP-induced anaphylaxis; LTP-induced anaphylaxis (NSAID independent); Healthy volunteer; Lipid transfer protein; Nonsteroidal anti-inflammatory drug; Galactose α-1,3-galactose
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2015.05.042

Lipid transfer protein (LTP), an abundant protein in fruits, vegetables, and nuts, is a common food allergen in Mediterranean areas causing diverse allergic reactions. Approximately 40% of food-related anaphylaxis induced by LTPs requires nonsteroidal anti-inflammatory drugs (NSAIDs) as a triggering cofactor. We sought to better understand the determinants of NSAID-dependent and NSAID-independent LTP-induced anaphylaxis (LTP-A). Selection of patients was based on a proved clinical history of NSAID-dependent or NSAID-independent anaphylaxis to LTPs, positive skin prick test response to LTPs, and serum LTP IgE. Whole-transcriptome (RNA sequencing) analysis of blood cells from 14 patients with NSAID-related LTP-A (NSAID-LTP-A), 7 patients with LTP-A, and 13 healthy control subjects was performed to identify distinct gene expression signatures. Expression of genes regulating gastrointestinal epithelial renewal was altered in both patient sets, particularly in those with LTP-A, who also presented with gene expression profiles characteristic of an inflammatory syndrome. These included altered B-cell pathways, increased neutrophil activation markers, and increased reactive oxygen species levels. Increased expression of the IgG receptor (CD64) in patients with LTP-A was mirrored by the presence of LTP-specific IgG1 and IgG3. Conversely, patients with NSAID-LTP-A were characterized by reduced expression of IFN-γ–regulated genes and IFN-γ levels, as well as upregulated expression of adenosine receptor 3 (ADORA3) and genes related to adenosine metabolism. Gene ontology analysis suggests disturbances in gut epithelial homeostasis in both groups with LTP-A, with potential integrity breaches in patients with LTP-A that might explain their distinct inflammatory signatures. Differential regulation in patients with LTP-A and those with NSAID-LTP-A of the IFN-γ pathway, IgG receptors, and ADORA3 might provide the pathogenic basis of their distinct responses.