Major Histocompatibility Complex Class I Chain-Related A and B (MICA and MICB) Gene, Allele, and Haplotype Associations With Dengue Infections in Ethnic Thais

Panpimon LuangtrakoolSasijit VejbaesyaKomon LuangtrakoolSomporn NgamhawornwongKusuma ApisawesSiripen KalayanaroojLouis R. MacareoStefan FernandezRichard G. JarmanRobert W.M. CollinsSteven T. CoxAnon SrikiatkhachornAlan L. RothmanHenry A.F. StephensThe Royal Free HospitalUniversity of Rhode Island Feinstein Providence CampusKing Mongkut's Institute of Technology LadkrabangArmed Forces Research Institute of Medical Sciences, ThailandWalter Reed Army Institute of ResearchFaculty of Medicine, Siriraj Hospital, Mahidol UniversityQueen Sirikit National Institute of Child HealthGuy's Hospital2020-08-252020-08-252020-08-04The Journal of infectious diseases. Vol.222, No.5 (2020), 840-846153766132-s2.0-85089124689https://repository.li.mahidol.ac.th/handle/20.500.14594/58030© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. BACKGROUND: Major histocompatibility complex class I chain-related (MIC) A and B (MICA and MICB) are polymorphic stress molecules recognized by natural killer cells. This study was performed to analyze MIC gene profiles in hospitalized Thai children with acute dengue illness. METHODS: MIC allele profiles were determined in a discovery cohort of patients with dengue fever or dengue hemorrhagic fever (DHF) (n = 166) and controls (n = 149). A replication cohort of patients with dengue (n = 222) was used to confirm specific MICB associations with disease. RESULTS: MICA*045 and MICB*004 associated with susceptibility to DHF in secondary dengue virus (DENV) infections (odds ratio [OR], 3.22; [95% confidence interval (CI), 1.18-8.84] and 1.99 [1.07-2.13], respectively), and MICB*002 with protection from DHF in secondary DENV infections (OR, 0.41; 95% CI, .21-.68). The protective effect of MICB*002 against secondary DHF was confirmed in the replication cohort (OR, 0.43; 95% CI, .22-.82) and was stronger when MICB*002 is present in individuals also carrying HLA-B*18, B*40, and B*44 alleles which form the B44 supertype of functionally related alleles (0.29, 95% CI, .14-.60). CONCLUSIONS: Given that MICB*002 is a low expresser of soluble proteins, these data indicate that surface expression of MICB*002 with B44 supertype alleles on DENV-infected cells confer a protective advantage in controlling DENV infection using natural killer cells.Mahidol UniversityMedicineMajor Histocompatibility Complex Class I Chain-Related A and B (MICA and MICB) Gene, Allele, and Haplotype Associations With Dengue Infections in Ethnic ThaisArticleSCOPUS10.1093/infdis/jiaa134