Immunoglobulin genes influence the magnitude of humoral immunity to cytomegalovirus glycoprotein B

Abstract

Human cytomegalovirus (HCMV) is a risk factor for many human diseases, but among exposed individuals, not everyone is equally likely to develop HCMV-spurred diseases, implying the presence of host genetic factors that might modulate immunity to this virus. Here, we show that antibody responsiveness to HCMV glycoprotein B (gB) is significantly associated with particular immunoglobulin GM (γ marker) genotypes. Anti-HCMV gB antibody levels were highest in GM 17/17 homozygotes, intermediate in GM 3/17 heterozygotes, and lowest in GM 3/3 homozygotes (28.2, 19.0, and 8.1 µg/mL, respectively; P=.014). These findings provide mechanistic insights in the etiopathogenesis of HCMV-spurred diseases.

Keywords: GM allotypes; candidate genes; glycoprotein B; human cytomegalovirus; humoral immunity.

Figure 1.

Box plots of anti-human cytomegalovirus glycoprotein B immunoglobulin G (IgG) antibody levels and GM 3/17 genotypes in Upper Midwest Health Study control participants. Bold horizontal lines denote median IgG antibody levels corresponding to the 3 genotypes, boxes denote interquartile ranges (IQRs), dotted lines denote 1.5 times the upper and lower limits of the IQRs, and open circles denote minima and maxima.