The effect of immunotherapy on cross-reactivity between house dust mite and other allergens in house dust mite -sensitized patients with allergic rhinitis

House dust mite (HDM) is a main perennial allergen causing allergic rhinitis (AR). It has been shown that HDM cross-reacts with a variety of other allergens. Presently, allergen-specific immunotherapy (AIT) is an effective way for management of mono-sensitized HDM+ AR patients. However, management approaches to polysensitized HDM-sensitized AR patients are not standardized yet.This article reviews the data available in the literature for cross-reactivity between HDM and inhalant or food allergens, the diagnosis of cross-reactivity in HDM-sensitized AR patients, and the effect of immunotherapy on cross-reactivity in HDM-sensitized AR patients; which may help to develop effective therapeutic strategies for management of polysensitized HDM-sensitized AR patients in the future.Pan-allergen proteins such as tropomyosin, arginine kinase (AK), glutathione S-transferase (GST), and hemocyanin are responsible for cross-reactivity between HDM and other allergens. To distinguish genuine or cross-reactive sensitization, molecular- or component-resolved diagnosis is suggested to apply in HDM-sensitized AR patients. The effect of HDM immunotherapy to treat the associated cross-reactivity in HDM-sensitized AR patients is still contradictory, and might be dependent on the degree of homology between two allergens. Furthermore, targeting tropomyosin might be a promising way to treat HDM patients with allergen cross-reactivity.AIT: allergen-specific immunotherapy; AK: arginine kinase; AR: allergic rhinitis; CRD: component-resolved diagnostics; Der f: Dermatophagoides farina; Der p: Dermatophagoides pteronyssinus; EAACI: European Academy of Allergy and Clinical Immunology; GST: glutathione S-transferase; GWAS: genome-wide association study; HDM: house dust mite; IgE: immunoglobulin E; RAST: radioallergosorbent test; sIgE: specific IgE; SIT: specific immunotherapy; SCIT: subcutaneous immunotherapy; SLIT: sublingual immunotherapy; SPT: skin prick test.