Pharmacogenetics of HLA gene polymorphisms in predicting response to Japanese cedar pollen sublingual immunotherapy

Abstract

Japanese cedar (JC) pollinosis is the most common type of seasonal allergic rhinitis (AR) prevalent in Japan, and the number of patients with JC pollinosis has markedly increased recently. Sublingual immunotherapy (SLIT) has been shown to significantly improve severe symptoms. In addition, SLIT can have a long-term effect despite discontinuation. Although most patients with AR respond favorably to SLIT, this therapy is ineffective in ~30% patients. Moreover, it can take ≥2 years to confirm the effectiveness of SLIT in treated patients. Therefore, an assay that identifies the treatment response of patients, as responders or non-responders prior to the implementation of SLIT, could be of great value. However, a predictive biomarker for SLIT efficacy is not available for patients with AR. We previously reported that amino acid changes in the allergen-binding pocket of HLA-DPβ1 were associated with sensitization to JC pollen, and subsequent development of JC pollinosis. This study aimed to investigate whether HLA-DPB1 gene is associated with SLIT responsiveness in patients with JC pollinosis. In total, 203 peak-symptomatic patients with JC pollinosis in the second season were considered eligible for the study; there were 160 responders and 43 non-responders. A non-responsive association with SLIT was observed among HLA-DPB1*05:01 carriers. Genotyping of HLA-DPB1 might serve as a predictive biomarker for response to SLIT among patients with JC pollinosis.