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Specific HLA genotypes confer susceptibility to acute necrotizing encephalopathy


Acute necrotizing encephalopathy (ANE) is a rare and severe syndrome of acute encephalopathy triggered by viral infections. Cytokine storm is considered as the main pathogenetic mechanism of ANE. ANE is prevalent in East Asia, suggesting the association of host genetic factors. To elucidate the genetic background of Japanese ANE, we examined genotypes of human leukocyte antigen (HLA)-A, C, B, DRB1, DQB1 and DPB1 in 31 patients. Significant positive association was observed in both the allele frequency and positivity of DRB1*09:01 (P=0.043 and 0.025, respectively), as well as those of DQB1*03:03 (P=0.034 and 0.026, respectively). The carrier frequency of DRB1*09:01 and DQB1*03:03 alleles was higher in the patients (45.16%) than in controls (28.57%). These alleles are more common in East Asian than in European populations, and are reportedly associated with various autoimmune diseases in Japanese patients. Our data provide further evidence that altered immune response based on individual HLA genotypes may contribute to ANE pathogenesis.

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We are indebted to the patients and their families who participated in the study, and to the doctors who treated the patients. We thank Kiyomi Noyama and Aya Shoda for their assistance. This study was supported by a Grant-in-aid for Scientific Research from the Japan Society for the Promotion of Science (No. 24390258) and by a Grant-in-Aid for Research on Policy for Intractable Diseases (H27-Nanjitou-Ippan-28) from the Ministry of Health, Labour and Welfare, Japan.

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Correspondence to A Hoshino.

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Hoshino, A., Saitoh, M., Miyagawa, T. et al. Specific HLA genotypes confer susceptibility to acute necrotizing encephalopathy. Genes Immun 17, 367–369 (2016).

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