Immunoglobulin allotypes and RELN alleles and humoral immunity to HSV1 in patients with Alzheimer's disease and matched controls.

BackgroundIncreasing evidence implicates herpes simplex virus type 1 (HSV1) in the pathogenesis of Alzheimer's disease (AD). The genome-wide association studies have not detected any genes regulating antibody responses to HSV1.ObjectiveTo determine whether the magnitude of antibody responses to HSV1 and to its glycoprotein D (gD) differed between AD patients and controls. Using a candidate gene approach, determine if the antibody responses were associated with immunoglobulin GM (γ marker) and KM (κ marker) allotypes-hereditary antigenic determinants of γ and κ chains, respectively. We also aimed to determine whether GM and KM allotypes epistatically interacted with an AD risk gene-reelin-encoding RELN (rs2299356)-and contributed to immunity to HSV1 and HSV1-gD.MethodsGenotyping was done by polymerase chain reaction-restriction fragment length polymorphism, TaqMan®, and rhAMP® SNP genotyping assays. IgG antibodies to HSV1 and HSV1-gD were measured by an enzyme-linked immunosorbent assay.ResultsAnti-HSV1 antibody levels were not significantly different between AD cases and controls; however, anti-HSV1-gD antibody levels were over two-fold higher (p < 0.0001) in AD cases compared to controls. GM 23 allele was associated with higher anti-HSV1 antibody levels in both cases and controls. Potential interaction between KM and RELN rs2299356 alleles on antibody responses to HSV1-gD was detected in AD cases, but not in controls.ConclusionsIn view of the fact that HSV1-gD is a vaccine candidate, the findings of higher anti-HSV1-gD antibody levels in AD patients and potential interaction of KM and RELN rs2299356 alleles in this study warrant additional large-scale multiethnic studies on this issue.