HLA Class I Supertype Associations With Clinical Outcome of Secondary Dengue Virus Infections in Ethnic Thais
Department of Medicine, Division of Infectious Diseases and Immunology
Medical Subject Headings
Adolescent; Case-Control Studies; Child; Child, Preschool; Cohort Studies; *Dengue Virus; *Ethnic Groups; Genes, MHC Class I; Genetic Predisposition to Disease; Humans; Logistic Models; Multivariate Analysis; Odds Ratio; Severe Dengue; Thailand
Immunology of Infectious Disease | Immunopathology | Infectious Disease | Virus Diseases
BACKGROUND: Human leukocyte antigen (HLA) supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system.
OBJECTIVES: To analyze HLA class I supertype associations with clinical outcome in hospitalized Thai children with acute dengue illness.
METHODS: Seven hundred sixty-two patients and population-matched controls recruited predominantly in Bangkok were HLA-A and -B typed. HLA supertype frequencies were compared and tested for significant dengue disease associations using logistic regression analyses. Multivariable models were built by conducting forward stepwise selection procedures.
RESULTS: In the final logistic regression model, the HLA-B44 supertype was protective against dengue hemorrhagic fever (DHF) in secondary infections (odds ratio [OR] = 0.46, 95% confidence interval [CI], .30-.72), while the HLA-A02 supertype (OR = 1.92, 95% CI, 1.30-2.83) and the HLA-A01/03 supertype (OR = 3.01, 95% CI, 1.01-8.92) were associated with susceptibility to secondary dengue fever. The B07 supertype was associated with susceptibility to secondary DHF in the univariate analysis (OR = 1.60, 95% CI, 1.05-2.46), whereas that was not retained in the final model.
CONCLUSIONS: As the HLA-B44 supertype is predicted to target conserved epitopes in dengue, our results suggest that B44 supertype-restricted immune responses to highly conserved regions of the dengue proteome may protect against secondary DHF.
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Citation: J Infect Dis. 2015 Sep 15;212(6):939-47. doi: 10.1093/infdis/jiv127. Epub 2015 Mar 4. Link to article on publisher's site
B44, HLA, Thais, associations, class I, dengue, infections, secondary, supertype
Vejbaesya, Sasijit; Thongpradit, Rungrot; Kalayanarooj, Siripen; Luangtrakool, Komon; Luangtrakool, Panpimon; Gibbons, Robert V.; Srinak, Duangporn; Ngammthaworn, Somporn; Apisawes, Kusuma; Yoon, In-Kyu; Thomas, Stephen J.; Jarman, Richard G.; Srikiatkhachorn, Anon; Green, Sharone; Chandanayingyong, Dasnayanee; Park, Sangshin; Friedman, Jennifer; Rothman, Alan L.; and Stephens, Henry A.F., "HLA Class I Supertype Associations With Clinical Outcome of Secondary Dengue Virus Infections in Ethnic Thais" (2015). University of Massachusetts Medical School Faculty Publications. 931.