Usefulness of antibody index assessment in cerebrospinal fluid from patients negative for total-IgG oligoclonal bands

Here we report on 21 patients with positive AI for either herpes simplex virus, varicella zoster virus, cytomegalovirus, measles virus, rubella virus, or Borrelia burgdorferi in the absence of total-IgG OCB and, accordingly, in the presence of a normal total-IgG CSF/serum ratio.Our findings indicate that AI testing should not generally be omitted in OCB-negative patients and provide a rationale for systematic and prospective studies on the comparative sensitivity and specificity of AI and total-IgG OCB testing in infectious and other diseases of the CNS.Testing for cerebrospinal fluid (CSF)-restricted total IgG oligoclonal bands (OCB) by isoelectric focusing is a highly sensitive method for detecting intrathecal IgG synthesis, but does not take into account antibody specificity. By contrast, antibody indices (AI) are assessed to test for antigen-specific intrathecal IgG synthesis [1]. It is unclear whether AI assessment is useful in OCB negative patients. Currently, clinicians often do not test for virus- or bacterium-specific AIs on cost grounds if evidence for intrathecal total IgG synthesis as detected by OCB testing is missing.Back in 1992, however, Felgenhauer and Reiber reported a positive varicella zoster virus (VZV)-specific AI in 6 total-IgG OCB-negative patients with VZV ganglionitis as well as in 4 total-IgG OCB-negative patients with VZV meningitis, suggesting that AI calculation might be more sensitive than total-IgG OCB testing [2]. Here, we report on 21 total-IgG OCB-negative patients with positive AI results for either herpes simplex virus (HSV), VZV, cytomegalovirus (CMV), measles virus (MV), rubella virus (RV), or Borrelia burgdorferi (Bb), thereby providing independent and corroborative evidence for Felgenhauer and Reiber’s hypothesis (see Table1 for details).Testing for OCB was performed by a CSF laboratory with long-standing expertise in the field that takes part in the official German external quality assessment organized by INSTAND e.V. twice