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HLA Class I Supertype Associations With Clinical Outcome of Secondary Dengue Virus Infections in Ethnic Thais.

AbstractBACKGROUND:
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.
AuthorsSasijit Vejbaesya, Rungrot Thongpradit, Siripen Kalayanarooj, Komon Luangtrakool, Panpimon Luangtrakool, Robert V Gibbons, Duangporn Srinak, Somporn Ngammthaworn, Kusuma Apisawes, In-Kyu Yoon, Stephen J Thomas, Richard G Jarman, Anon Srikiakthachorn, Sharone Green, Dasnayanee Chandanayingyong, Sangshin Park, Jennifer Friedman, Alan L Rothman, Henry A F Stephens
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 212 Issue 6 Pg. 939-47 (Sep 15 2015) ISSN: 1537-6613 [Electronic] United States
PMID25740956 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Copyright© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
Topics
  • Adolescent
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dengue Virus
  • Ethnicity
  • Genes, MHC Class I (physiology)
  • Genetic Predisposition to Disease
  • Humans
  • Logistic Models
  • Multivariate Analysis
  • Odds Ratio
  • Severe Dengue (ethnology, immunology, virology)
  • Thailand (epidemiology)

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