doi: 10.1111/cea.12578 Clinical & Experimental Allergy, 45, 1542–1553 ORIGINAL ARTICLE Clinical Mechanisms in Allergic Disease © 2015 John Wiley & Sons Ltd Initial immunological changes as predictors for house dust mite immunotherapy response E. G omez 1, *, T. D. Fern andez 1, *, I. Do~ na 2 , C. Rondon 2 , P. Campo 2 , F. Gomez 2 , M. Salas 2 , M. Gonzalez 1 , J. R. Perkins 1 , F. Palomares 1 , M. Blanca 2 , M. J. Torres 2, * and C. Mayorga 1, * 1 Research Laboratory-Allergy Unit, IBIMA-Regional University Hospital of M alaga, UMA, Malaga, Spain and 2 Allergy Service, IBIMA-Regional University Hospital of M alaga, UMA, Malaga, Spain Clinical & Experimental Allergy Correspondence: Cristobalina Mayorga, Research Laboratory-Allergy Service, Pavilion 5, Basement, University Hospital of Malaga (Pavilion C), Plaza del Hospital Civil, 29009 Malaga, Spain. E-mail: lina.mayorga@ibima.eu Cite this as: E. G omez, T. D. Fern andez, I. Do~ na, C. Rondon, P. Campo, F. Gomez, M. Salas, M. Gonzalez, J. R. Perkins, F. Palomares, M. Blanca, M. J. Torres, and C. Mayorga, Clinical & Experimental Allergy, 2015 (45) 1542–1553. Summary Background Although specific immunotherapy is the only aetiological treatment for aller- gic disorders, the underlying mechanisms are not fully understood. Specific immunother- apy induces changes in lymphocyte Th subsets from Th2 to Th1/Treg. Whether differences in immunological patterns underlie patient response to immunotherapy has not yet been established. Objectives We studied the immunological changes occurring during a 1-year period of Dermatophagoides pteronyssinus (DP) immunotherapy and their relation with clinical out- come. Methods We included 34 patients with DP allergy who received subcutaneous specific immunotherapy (SCIT) for 1 year. Following treatment, patients were classified as responders or non-responders. Fourteen allergic subjects who did not receive SCIT were included as controls. Peripheral blood was obtained at 0, 1, 3, 6 and 12 months and cul- tured with nDer p 1. Phenotypic changes, cytokine production and basophil response were analysed by flow cytometry; transcription factors were measured by mRNA quantification. Serum immunoglobulin levels were also measured. Results After 1 year of SCIT, 82% of cases showed improved symptoms (responders). Although increases in sIgG4 were observed, BAT reactivity was not modified in these patients. Increases in T-BET/FOXP3 as well as nDer p 1-specific Th1/Treg frequencies were also observed, along with a decrease in Th2, Th9 and Th17. These changes corresponded to changes in cytokine levels. Conclusion Patients who respond well to DP-SCIT show immunological differences com- pared to non-responders. In responders, basal differences include a lower frequency of Th1 and higher frequencies of Th2, Th9 and Th17 cells. After 1 year of treatment, an increased production of sIgG4 was observed in responders, along with a change in Th2 response towards Th1/Treg. Keywords allergic rhinitis, basophils, cytokines, Dermatophagoides pteronyssinus, immu- noglobulins, specific immunotherapy, T cells Submitted 5 November 2014; revised 14 May 2015; accepted 15 May 2015 Introduction Allergic rhinitis (AR) is a common disorder that affects 500 million people world-wide [1]. It adversely impacts the social life, school performance and work productiv- ity of patients [2, 3], and produces a large economic burden on governments [4]. Frequently, AR presents comorbidities with allergic conjunctivitis as well as other respiratory disorders such as rhinosinusitis, and especially asthma [5–7]. Among inhaled allergens, Der- matophagoides pteronyssinus (DP) is considered one of the major aetiological factors world-wide [1, 8]. Current therapies include those based on the strict avoidance of causative allergens, which can be difficult, or the use of pharmacotherapy that allows a transient reduction of the symptoms, but not a cure. Specific *The Authors contributed equally to this manuscript.