HLA class I and class II associations were examined in relation to measles virus-specific
cytokine responses in 339 healthy children who had received two doses of live attenuated
measles vaccine. Multivariate linear regression modeling analysis revealed suggestions of associations between the expression of DPA1*0201 (p=0.03) and DPA1*0202 (p=0.09) alleles and
interleukin-2 (IL-2)
cytokine production (global p-value 0.06). Importantly,
cytokine production and DQB1 allele associations (global p-value 0.04) revealed that the alleles with the strongest association with
IL-10 secretion were DQB1*0302 (p=0.02), DQB1*0303 (p=0.07) and DQB1*0502 (p=0.06).
Measles-specific
IL-10 secretion associations approached significance with DRB1 and DQA1 loci (both global p-values 0.08). Specifically, suggestive associations were found between DRB1*0701 (p=0.07), DRB1*1103 (p=0.06), DRB1*1302 (p=0.08), DRB1*1303 (p=0.06), DQA1*0101 (p=0.08), and DQA1*0201 (p=0.04) alleles and
measles-induced
IL-10 secretion. Further, suggestive association was observed between specific DQA1*0505 (p=0.002) alleles and
measles-specific
IL-12p40 secretion (global p-value 0.09) indicating that
cytokine responses to
measles antigens are predominantly influenced by HLA class II genes. We found no associations between any of the alleles of
HLA A, B, and Cw loci and
cytokine secretion. These novel findings suggest that HLA class II genes may influence the level of
cytokine production in the adaptive immune responses to
measles vaccine.