Human leukocyte antigen and interleukin 2, 10 and 12p40 cytokine responses to measles: Is there evidence of the HLA effect?

Abstract

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). Measlesspecific 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.

Vaccinomics and a New Paradigm for the Development of Preventive Vaccines Against Viral Infections

“…We have also demonstrated that HLA genes significantly influence CMI responses following MMR vaccination, but do not explain all of the variance in immune responses seen within the population (Ovsyannikova et al, 2005b(Ovsyannikova et al, , 2005c(Ovsyannikova et al, , 2006a(Ovsyannikova et al, , 2007d. For example, we have estimated that the HLA genes explain approximately 9% of the variance observed in rubella antibody levels.…”

“…Among immune response genes, human leukocyte antigen (HLA) genes are critical genes in host immunity and vaccine immune responses. Several findings in regard to measles, mumps, rubella, influenza, and vaccinia vaccine antigens and HLA genetics were previously reported, demonstrating that HLA genes are important determinants of variability in vaccine response (Ovsyannikova et al, 2004a(Ovsyannikova et al, , 2004b(Ovsyannikova et al, , 2005a(Ovsyannikova et al, , 2006aPoland et al, 2001Poland et al, , 2008a. Our research indicates that specific HLA class I and class II gene polymorphisms, including haplotypes and supertypes, are associated with variations in MMR vaccine-induced antibody levels, demonstrating that individual genetic variation or immunogenetic profiling is important in explaining variations in protective antibody levels following vaccination (Ovsyannikova et al, 2004a(Ovsyannikova et al, , 2004b(Ovsyannikova et al, , 2005a(Ovsyannikova et al, , 2006b.…”

Consistency of HLA associations between two independent measles vaccine cohorts: A replication study

“…We leveraged work we previously accomplished by including subjects who had participated in our prior measles vaccine study [8;11–13]. Details of recruitment of this study cohort (n=346, 12–18 years of age) are described in our previous HLA association publications [8;9;13;15].…”

A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32

“…36 In addition, HLA class II alleles can influence CD4 ϩ T-cell polarization to either the Th1 or Th2 subtype with subsequent alterations in cytokine responses. [37][38] NSHL tumors produce large amounts of Th2 and inflammatory cytokines, 39 and susceptibility is associated with increased Th2 and decreased Th1 cytokine production. 13,[15][16] Therefore, our SNPs could code for HLA allele variation, which in turn could affect antigen-binding capacity and CD4 ϩ cell polarization, thereby contributing to a protective or risk immunophenotype.…”