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

¹From the Center for Neurobiology and Vaccine Development, Ophthalmology Research, Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles, California; ²The Eye Institute, University of California Irvine, School of Medicine, Irvine, California; ³Division of Infectious Diseases, Cedars-Sinai Medical Center, San Diego, California; and ⁵La Jolla Institute for Molecular Medicine, San Diego, California.

PURPOSE. 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.

This article has been cited by other articles:

				K. R. Mott, A. A. Chentoufi, D. Carpenter, L. BenMohamed, S. L. Wechsler, and H. Ghiasi The Role of a Glycoprotein K (gK) CD8+ T-Cell Epitope of Herpes Simplex Virus on Virus Replication and Pathogenicity Invest. Ophthalmol. Vis. Sci., June 1, 2009; 50(6): 2903 - 2912. [Abstract] [Full Text] [PDF]

				K. R. Mott, G.-C. Perng, Y. Osorio, K. G. Kousoulas, and H. Ghiasi A Recombinant Herpes Simplex Virus Type 1 Expressing Two Additional Copies of gK Is More Pathogenic than Wild-Type Virus in Two Different Strains of Mice J. Virol., December 1, 2007; 81(23): 12962 - 12972. [Abstract] [Full Text] [PDF]