Evidence for antigen-specific immune deviation in patients with acute retinal necrosis

Background: Because experimental acute retinal necrosis (ARN) induced by he rpes simplex virus in mice develops only if mice fail to acquire virus-spec ific delayed hypersensitivity (DH), although they produce antiviral antibod ies (ie, anterior chamber-associated immune deviation), we sought to determ ine whether a similar inverse correlation exists for patients with varicell a-zoster virus (VZV)-induced ARN. Design: Patients with acute, VZV-induced ARN and age-matched control subjec ts were skin tested with VZV and purified protein derivative antigens to Ev aluate DH. Varicella-zoster virus-induced ARN was diagnosed using polymeras e chain reaction and intraocular antibody quotient. Serum samples were coll ected and analyzed for anti-VZV and anti-herpes simplex virus antibody tite rs. Acute retinal necrosis activity was assessed clinically, and DH skin te sts were repeated 3 months after onset when ocular recovery had taken place . Results: Whereas controls displayed intense DH when tested with VZV and pur ified protein derivative antigens, a subset of patients with ARN displayed absent VZV specific DH (although their purified protein derivative response s were normal). Patients with the most severe ARN had the lowest DH respons es to VZV antigens. Serum anti-VZV antibody titers were higher in patients with ARN than in controls, and antiviral titer correlated inversely with th e intensity of anti-VZV DH responses. Varicella-zoster virus-specific DH re sponses were restored in patients who recovered from ARN. Conclusion: Varicella-zoster virus-ARN develops in a setting where DH react ivity to viral antigens is absent, implying that virus-specific DH might am eliorate tile severity of ARN. Clinical Relevance: Linking virus-specific DI-I to vulnerability to ARN in individuals infected with VZV might reveal an underappreciated pathogenic m echanism.