Association of Japanese cedar pollinosis and sensitization with HLA-DPB1 in the Japanese adolescent

Abstract

Background: Allergic rhinitis (AR) is a heterogeneous disorder that significantly affects daily activity, work productivity, sleep, learning, and quality of life in all generations. Japanese cedar (JC) pollen is the most common allergen responsible for the development of AR in Japan. AR caused by JC pollen is considered to be a multifactorial inheritance disease that is caused by both environmental and genetic factors. The aim of this study was to investigate whether Human Leukocyte Antigen-DPB1 (HLA-DPB1) is associated with JC sensitization/pollinosis. Methods: Subjects in the present study were 544 students at the University of Tsukuba from 2013 to 2015. PCR-SSOP was performed to determine each individual's HLA-DPB1 alleles. Logistic regression analysis was performed to examine relationships between JC-related phenotypes and alleles/amino acid polymorphisms of HLA-DPB1. Results: HLA-DPB1*02 allele were significantly associated with both JC sensitization/pollinosis (q < 0.05). Furthermore, HLA-DPB1*02:01 and HLA-DPB1*02:02 had a protective tendency for JC sensitization/pollinosis, and HLA-DPB1*05:01 had a susceptible tendency for sensitization (P < 0.05). In amino acid polymorphism analyses, Glutamic acid in position 69, Glycine-Glycine-Proline-Methionine in positions 84–87, Threonine in position 170 and Methionine in position 205 were also observed to have a protective tendency for JC sensitization (P < 0.05). Amino acid positions 69 and 84–87 were located in binding pocket 5 and 1 of HLA-DPβ1, respectively. Conclusions: Amino acid changes in the allergen-binding pocket of HLA-DPβ1 are likely to influence pollinosis/sensitization to the allergenic peptide of JC pollen and determine the pollinosis risk for each individual exposed to JC pollen.

Keywords

• Allergic rhinitis
• Allergic sensitization
• Epidemiological survey
• HLA
• Japanese cedar pollinosis