Acute retinal necrosis six years after herpes simplex encephalitis: An elusive immune deficit suggested by insufficient test sensitivity

Abstract

A patient presented with acute retinal necrosis of the left eye. Demonstration of herpes simplex virus (HSV) DNA in the aqueous humour confirmed the diagnosis. Negative results of HSV type-specific antibody tests based on gG antigens suggested a primary HSV infection. However, the patient had a past history of laboratory-confirmed herpes simplex encephalitis 6 years ago. Using antibody tests based on whole viral lysate antigens, he was seropositive from the onset, and immunoblot testing confirmed a lack of anti-gG reactivity. To be able to assess whether this might be related to the apparent inability of his immune system to suppress clinically symptomatic HSV infection, serial samples were tested by an HSV neutralisation test and a whole-blood flow cytometric assay to determine the frequency of HSV-specific CD4 lymphocytes. However, this did not yield evidence of obvious immunodeficiency; the patient reacted similarly to known positive controls by both assays. Although type-specific HSV serological tests based on gG are generally more specific than those based on whole viral lysate antigens, they have a somewhat lower sensitivity, as a certain percentage of HSV-infected individuals do not develop antibodies against gG, and others may suffer a secondary loss of anti-gG reactivity. Thus there is a risk of missing individual infected patients. Unless this potential problem is recognised, serious consequences might possibly result. We therefore urge virologists and clinicians to exercise great care if highly specific antibody assays based on recombinant proteins are employed.

Impaired Plasmacytoid Dendritic Cell Innate Immune Responses in Patients with Herpes Virus-Associated Acute Retinal Necrosis

“…HSV-1 encephalitis preceding ARN was described by our group (36) and others (51)(52)(53)(54). Elevated PDC counts in cerebrospinal fluid were detected in neuroinflammatory conditions, suggesting that PDC may contribute to the orchestration of local immune responses in this immune-privileged compartment (26).…”

Acute retinal necrosis in a patient with remote severe herpes simplex encephalitis

“…Although uncommon, other cases of ARN associated with HSV encephalitis have been reported. A search of English PubMed articles about patients diagnosed with both ARN and HSV-1 or HSV-2 encephalitis revealed 34 case reports that are summarised in table 1 8-35. Median age was 44.5 years (range of 23 days to 68 years old) and male gender was reported in 24/36 (67%) cases.…”

Acute retinal necrosis as a late sequela of herpes simplex type 1 encephalitis in a child

“…There have been numerous reports of HSV-1 as a cause of acute retinal necrosis in adults, but in our literature review, we were able to only find two such reports in older children (11 and 16 years of age). [3][4][5][6][7] In the case of the 11-year-old, there was no definitive diagnosis of previous HSV-1 infection. An immunologic study by Preise et al 5 showed a relative immunodeficiency against certain HSV-1 antigens in an adult with late-presenting acute retinal necrosis after encephalitis, suggesting a possible immunologic propensity for reactivation or reinfection.…”