Published online May 1, 2008
PEDIATRICS Vol. 121 No. 5 May 2008, pp. e1091-e1099 (doi:10.1542/peds.2007-1575)
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ARTICLE

Human Leukocyte Antigen and Cytokine Receptor Gene Polymorphisms Associated With Heterogeneous Immune Responses to Mumps Viral Vaccine

Inna G. Ovsyannikova, PhDa,b, Robert M. Jacobson, MDa,b,c, Neelam Dhiman, PhDa, Robert A. Vierkant, MSd, V. Shane Pankratz, PhDd and Gregory A. Poland, MDa,b

a Mayo Vaccine Research Group
b Program in Translational Immunovirology and Biodefense
Departments of c Pediatric and Adolescent Medicine
d Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota

OBJECTIVES. Mumps outbreaks continue to occur throughout the world, including in highly vaccinated populations. Vaccination against mumps has been successful; however, humoral and cellular immune responses to mumps vaccines vary significantly from person to person. We set out to assess whether HLA and cytokine gene polymorphisms are associated with variations in the immune response to mumps viral vaccine.

METHODS. To identify genetic factors that might contribute to variations in mumps vaccine–induced immune responses, we performed HLA genotyping in a group of 346 healthy schoolchildren (12–18 years of age) who previously received 2 doses of live mumps vaccine. Single-nucleotide polymorphisms (minor allele frequency of >5%) in cytokine and cytokine receptor genes were genotyped for a subset of 118 children.

RESULTS. Median values for mumps-specific antibody titers and lymphoproliferative stimulation indices were 729 IU/mL and 4.8, respectively. Girls demonstrated significantly higher mumps antibody titers than boys, indicating gender-linked genetic differences in humoral immune response. Significant associations were found between the HLA-DQB1*0303 alleles and lower mumps-specific antibody titers. An interesting finding was the association of several HLA class II alleles with mumps-specific lymphoproliferation. Alleles of the DRB1 (*0101, *0301, *0801, *1001, *1201, and *1302), DQA1 (*0101, *0105, *0401, and *0501), and DQB1 (*0201, *0402, and *0501) loci were associated with significant variations in lymphoproliferative immune responses to mumps vaccine. Additional associations were observed with single-nucleotide polymorphisms in the interleukin-10RA, interleukin-12RB1, and interleukin-12RB2 cytokine receptor genes. Minor alleles for 4 single-nucleotide polymorphisms within interleukin-10RA and interleukin-12RB genes were associated with variations in humoral and cellular immune responses to mumps vaccination.

CONCLUSIONS. These data suggest the important role of HLA and immunoregulatory cytokine receptor gene polymorphisms in explaining variations in mumps vaccine–induced immune responses.

Key Words: mumps • mumps vaccine • immunity • cellular • antibodies • viral • lymphocyte proliferation • genes • HLA complex • single-nucleotide polymorphisms

Abbreviations: MMR—measles-mumps-rubella • IL—interleukin • IgG—immunoglobulin G • EIA—enzyme immunoassay • SI—stimulation index • PCR—polymerase chain reaction • SNP—single-nucleotide polymorphism • IFN-{gamma}—{gamma} interferon • IQR—interquartile range • STAT—signal transducer and activator of transcription

Accepted Oct 16, 2007.