Role of Anti–Glycoproteins D (Anti–gD) and K (Anti–gK) IgGs in Pathology of Herpes Stromal Keratitis in Humans

Abstract

To assess the relative impact of antibodies specific for HSV-1 glycoproteins on eye disease in response to HSV-1 infection, the composition of antibodies specific for 10 of the viral glycoproteins, and the effect of anti-glycoprotein (g)D and anti-gK antibodies on antibody-dependent enhancement (ADE). In a prospective case-control study, sera from patients with a history of herpes stromal keratitis (HSK) were compared with sera from nonocular HSV-1-seropositive and HSV-seronegative control subjects. HSV-1 neutralizing antibody titer and type-specific IgG and IgM were measured. In addition, the presence of anti-HSV-1 gD and gK antibodies in the sera of all patients also was determined by ELISA using gD and gK antigens. Finally, the role of anti-gD- and gK-specific antibodies to ADE was investigated. Average neutralizing antibody titers and levels of HSV-1 IgG were similar between HSK- and non-HSK-seropositive patients. However, the contribution of gD to the neutralizing antibody titer in HSK sera was significantly lower than that in non-HSK-seropositive patients, despite higher anti-gD ELISA titers. Overall, sera from patients with HSK had higher anti-gK antibody titers and induced ADE in vitro compared with non-HSK or seronegative sera. The ADE response in HSK sera was attributed to anti-gK antibody. These results suggest that sera from HSK patients had higher anti-gD and -gK antibody titers than sera from seropositive patients who had no history of HSK despite similar levels of neutralizing antibody titers and HSV-1 IgG, that HSK sera induced ADE whereas sera from non-HSK patients did not induce ADE, and that anti-gD antibody in sera of HSK patients contributed less to the HSV-1 neutralization antibody titer than did sera from non-HSK patients.