P060A MICA typing by NGS revealed the association of MICA GENE polymorphism with specific IgE production in cedar pollen allergy

Aim We have found the association of Japanese Cedar Pollinosis (JCPsis) with SNPs near MICA gene by SNPs typing in HLA gene region. In this study, the association was clarified by MICA gene typing using amplicon sequenceing method by NGS. Methods DNAs from 178 JCPsis patients, 185 healthy controls were tested allele types of MICA and HLA by HLA and KIR typing Kit (Scisco Genetics Inc) on MiSeq (Illumina Inc,). Serum samples from them were titrated for the presence of specific IgE antibodies to Japanese cedar pollen(JCP), orchard grass pollen, mugwort pollen, u0026 house dust mite by radioallergosorbent test. Results Though all controls were selected not to have any symptom of pollinosis, only 101 in 185 individuals were specific IgE negative to all allergens tested, and 84 individuals were positive to one or more allergens including JCP. Therefore, the control group was divided into two groups, specific IgE negative and positive to allergens. The significant association of MICA with JCPsis was found only in analysis using IgE negative control group. IgE positive control group showed no association. MICA*008((P = 0.0036, odds = 0.5) u0026 MICA*027 (P = 0.016, odds = 0.55) showed strong reverse association. Conclusions MICA*008 is lacked a part of trans-membrane region and produce soluble protein. Furthermore, 008 and 027 has the haplotype of 175Gly, 213 Ile, 251Arg which are reported to relate with MICA shedding. This haplotype associate with JCPsis strongly (P = 0.0000399, Odds = 0.46). It is speculated that soluble MICA may suppress IgE production by binding NKG2D and inactivating NK cell, and suppress pollinosis. This speculation is also supported by the report that NKG2D is critical for allergy.