Abstract
Allergen immunotherapy (AIT) is the only treatment that can change the course of allergic diseases. However, there has not been any research on metabolic reactions in relation to AIT with single or mixed allergens. In this study, patients with allergic rhinitis caused by Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) were treated with single-mite (Der p) and double-mite (Der p:Der f = 1:1) subcutaneous immunotherapy (SCIT), respectively. To compare the efficacy and the dynamic changes of inflammation-related single- and double-species mite subcutaneous immunotherapy (SM-SCIT and DM-SCIT), we performed visual analogue scale (VAS) score, rhinoconjunctivitis quality of life questionnaire (RQLQ) score and serum metabolomics in allergic rhinitis patients during SCIT. VAS and RQLQ score showed no significant difference in efficacy between the two treatments. A total of 57 metabolites were identified, among which downstream metabolites (5(S)-HETE (Hydroxyeicosatetraenoic acid), 8(S)-HETE, 11(S)-HETE, 15(S)-HETE and 11-hydro TXB2) in the ω-6-related arachidonic acid and linoleic acid pathway showed significant differences after approximately one year of treatment in SM-SCIT or DM-SCIT, and the changes of the above serum metabolic components were correlated with the magnitude of RQLQ improvement, respectively. Notably, 11(S)-HETE decreased more with SM-SCIT, and thus it could be used as a potential biomarker to distinguish the two treatment schemes. Both SM-SCIT and DM-SCIT have therapeutic effects on patients with allergic rhinitis, but there is no significant difference in efficacy between them. The reduction of inflammation-related metabolites proved the therapeutic effect, and potential biomarkers (arachidonic acid and its downstream metabolites) may distinguish the options of SCIT.
Highlights
Allergic rhinitis (AR), known as anaphylactic rhinitis, mainly refers to noninfectious inflammatory diseases of the nasal mucosa caused by exposure to atopic allergens [1]
Metabolomics and multivariate analysis (Figures 3 and 4, and Supplementary Figure S2) results showed that the downstream products of linoleic acid metabolism (i.e., 13-HODE, 9-HPODE, 5(S)-HETE, 8(S)-HETE, 11(S)-HETE, 15(S)-HETE and 11- dehydro-TXB2), which were associated with the arachidonic acid (AA) pathway, decreased significantly, and the α-linolenic acid and eicosapentaenoic acid (EPA) pathway downstream products 5-HEPE and 12-HEPE were significantly different
The current research on 11(S)-HETE is still superficial, but we found that the level of 11(S)-HETE in patients who received SM-subcutaneous immunotherapy (SCIT) decreased faster than those who received double-mite subcutaneous immunotherapy (DM-SCIT), which may be due to its positive correlation with inflammation
Summary
Allergic rhinitis (AR), known as anaphylactic rhinitis, mainly refers to noninfectious inflammatory diseases of the nasal mucosa caused by exposure to atopic allergens [1]. Regarding the selection of cross-reactive allergens as immune agents in AIT, the World Health Organization and the European Academy of Allergy and Clinical Immunology have declared that selecting a vaccine with mixed or single allergens for immunotherapy would not produce an actual difference, because the two allergens have the same antigens epitope and bind to the same specific IgE antibody, which causes the same allergic reaction [15], and major sensitization proteins with over 80% similarity in the sequence [16]. The American Academy of Allergy, Asthma and Immunology (AAAAI) recommends that it may be imperative to limit the allergen types used as immune agents during immunotherapy, with cross-allergens causing the same immune response, based on the consideration of adverse reactions, allergen dilution effects and curative effects, so that a single antigen can be more effectively achieved. No comparative study is currently available on the clinical efficacy and inflammatory response of HDM single-allergen immunotherapy and HDM mixed-allergen immunotherapy
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