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Background: HLA supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system. Despite many reports of HLA allele associations with dengue, there have to date been no studies of HLA supertype associations with disease.

Objectives: To analyse HLA class I supertypes in hospitalised Thai children with acute dengue illness.

Methods: 762 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. Final 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 (OR=0.46, 95%CI=0.30-0.72), 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.