University of Massachusetts Medical School Faculty Publications

Title

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

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

9-15-2015

Document Type

Article

Subjects

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

Disciplines

Immunology of Infectious Disease | Immunopathology | Infectious Disease | Virus Diseases

Abstract

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.

Keywords

B44, HLA, Thais, associations, class I, dengue, infections, secondary, supertype

Rights and Permissions

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

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of infectious diseases

PubMed ID

25740956