Evidence for antigen-specific immune deviation in patients with acute retinal necrosis.
BACKGROUND
Because experimental acute retinal necrosis (ARN) induced by herpes simplex virus in mice develops only if mice fail to acquire virus-specific delayed hypersensitivity (DH), although they produce antiviral antibodies (ie, anterior chamber-associated immune deviation), we sought to determine whether a similar inverse correlation exists for patients with varicella-zoster virus (VZV)-induced ARN.


METHODS
Patients with acute, VZV-induced ARN and age-matched control subjects were skin tested with VZV and purified protein derivative antigens to evaluate DH. Varicella-zoster virus-induced ARN was diagnosed using polymerase chain reaction and intraocular antibody quotient. Serum samples were collected and analyzed for anti-VZV and anti-herpes simplex virus antibody titers. Acute retinal necrosis activity was assessed clinically, and DH skin tests were repeated 3 months after onset when ocular recovery had taken place.


RESULTS
Whereas controls displayed intense DH when tested with VZV and purified protein derivative antigens, a subset of patients with ARN displayed absent VZV-specific DH (although their purified protein derivative responses were normal). Patients with the most severe ARN had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in patients with ARN than in controls, and antiviral titer correlated inversely with the intensity of anti-VZV DH responses. Varicella-zoster virus-specific DH responses were restored in patients who recovered from ARN.


CONCLUSIONS
Varicella-zoster virus-ARN develops in a setting where DH reactivity to viral antigens is absent, implying that virus-specific DH might ameliorate the severity of ARN.


CONCLUSIONS
Linking virus-specific DH to vulnerability to ARN in individuals infected with VZV might reveal an underappreciated pathogenic mechanism.
Kezuka
T
T
Department of Ophthalmology, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. tkezuka@tokyo-med.ac.jp
Sakai
J
J
Usui
N
N
Streilein
J W
JW
Usui
M
M
D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D006563:Herpes Zoster Ophthalmicus / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000821:virology; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015882:Retinal Necrosis Syndrome, Acute / Q000276:immunology* / Q000821:virology; D012882:Skin Tests; D014373:Tuberculin / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D017931:DNA Primers; D014373:Tuberculin