An isoelectric focusing study in herpes simplex virus encephalitis

Abstract

To establish an early reliable diagnostic test for herpes simplex virus (HSV) type 1 encephalitis (HSVE), we used isoelectric focusing (IEF) and an IEF‐overlay technique with radiolabeled HSV glycoprotein B (gB) to study 7 serum and 12 cerebrospinal fluid (CSF) samples from 12 patients with presumed or biopsy‐proved HSVE. Blood‐brain barrier damage and increased intra‐blood‐brain barrier IgG synthesis were detected in 5 of the 7 patients with HSVE. CSF oligoclonal bands were found in 6 of 11 patients. Using an IEF‐overlay technique, we detected anti‐gB antibody in all serum (7 of 7) and in 10 of 12 CSF samples. Anti‐gB antibody was found in 4 of 6 CSF specimens obtained within the first week of disease (days 3 to 5) and in all samples collected later in the disease. The pH range of anti‐gB antibody activity was broad (4.5 to 9.5), indicating a heterogeneous immune response to HSV. A hematogenous origin of the CSF antibody was suggested because anti‐gB antibody appeared in serum before matched CSF and because both serum and matched CSF had a similar antibody IEF pattern. Local production of anti‐gB antibody was suggested in some cases because of a greater prominence of anti‐gB antibody in CSF than in matched sera and because CSF oligoclonal bands had anti‐gB antibody activity. In contrast, only one of 6 CSF samples from patients with multiple sclerosis had gB antibody activity; in this case, anti‐gB antibody activity did not correspond in isoelectric point location to oligoclonal bands. The IEF‐HSV‐gB overlay technique may be a useful diagnostic test for HSVE and a valuable research tool for studying qualitative aspects of the HSV humoral immune response.