HLA Class I Supertype Associations With Clinical Outcome of Secondary Dengue Virus Infections in Ethnic Thais.
BACKGROUND
Human leukocyte antigen (HLA) supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system.


OBJECTIVE
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.
Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University.
Sasijit
S
Vejbaesya
Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University.
Rungrot
R
Thongpradit
Queen Sirikit National Institute of Child Health.
Siripen
S
Kalayanarooj
Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University.
Komon
K
Luangtrakool
Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University.
Panpimon
P
Luangtrakool
Department of Virology, Armed Forces Research Institute of Medical Science, Bangkok, Thailand.
Robert V
RV
Gibbons
Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University.
Duangporn
D
Srinak
Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University.
Somporn
S
Ngammthaworn
Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University.
Kusuma
K
Apisawes
Department of Virology, Armed Forces Research Institute of Medical Science, Bangkok, Thailand.
In-Kyu
IK
Yoon
Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland.
Stephen J
SJ
Thomas
Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland.
Richard G
RG
Jarman
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester.
Anon
A
Srikiakthachorn
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester.
Sharone
S
Green
Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University.
Dasnayanee
D
Chandanayingyong
Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University.
Sangshin
S
Park
Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown University.
Jennifer
J
Friedman
Institute for Immunology and Informatics, University of Rhode Island, Providence.
Alan L
AL
Rothman
Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University UCL Centre for Nephrology and Anthony Nolan Laboratories, Royal Free NHS Foundation Trust, Royal Free Hospital, London, United Kingdom.
Henry A F
HA
Stephens
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003716:Dengue Virus; D005006:Ethnicity; D005805:Genes, MHC Class I / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D015999:Multivariate Analysis; D016017:Odds Ratio; D019595:Severe Dengue / Q000208:ethnology / Q000276:immunology / Q000821:virology*; D013785:Thailand / Q000453:epidemiology
B44; HLA; Thais; associations; class I; dengue; infections; secondary; supertype