Role of anti-glycoproteins D (anti-gD) and K (anti-gK) IgGs in pathology of herpes stromal keratitis in humans.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Mott
Kevin R
KR
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles, California 90048, USA.
Osorio
Yanira
Y
Maguen
Ezra
E
Nesburn
Anthony B
AB
Wittek
Alec E
AE
Cai
Steve
S
Chattopadhyay
Subhendra
S
Ghiasi
Homayon
H
D000293:Adolescent; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D016022:Case-Control Studies; D003319:Corneal Stroma / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000821:virology; D008297:Male; D011446:Prospective Studies; D011817:Rabbits; D014759:Viral Envelope Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C072448:UL53 protein, Human herpesvirus 1; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C039447:glycoprotein D, Human herpesvirus 1