The fraction of varicella zoster virus-specific antibodies among all intrathecally-produced antibodies discriminates between patients with varicella zoster virus reactivation and multiple sclerosis

BACKGROUND: Primary infection with or reactivation of varicella zoster virus (VZV) can cause neurologic complications, which typically result in an intrathecal production of VZV-specific antibodies. Intrathecal antibodies to VZV are detectable by an elevated antibody index (AI). However, elevated VZV AIs are also found in more than half of patients with multiple sclerosis (MS), where they are thought to be part of a polyspecific intrathecal immune response. Determination of the fraction of intrathecally-produced virus-specific antibodies among all intrathecally produced antibodies may discriminate between virus-specific and polyspecific intrathecal immune responses, but the fraction of intrathecally-produced VZV-specific immunoglobulin (Ig)G of the total intrathecally produced IgG (F(S) anti-VZV) in patients with MS and VZV reactivation has hitherto not been compared. FINDINGS: F(S) anti-VZV was calculated in patients with a clinically isolated syndrome suggestive of multiple sclerosis (MS) or MS (n = 20) and in patients with VZV reactivation (7 samples from 5 patients), which all had elevated VZV AIs. The median F(S) anti-VZV was 35-fold higher in patients with VZV reactivation (45.1%, range 13.5-73%) than in patients with CIS/MS (1.3%, range 0.3-5.3%; p = 0.0001). While there was thus no overlap of F(S) anti-VZV values between groups, VZV AIs completely overlapped in patients with CIS/MS (1.6-14.8) and VZV reactivation (2.1-8.1). CONCLUSIONS: The fraction of intrathecally-produced VZV-specific IgG of the total intrathecally produced IgG discriminates between patients with VZV reactivation and MS. Our results provide further evidence that intrathecally-produced VZV antibodies are part of the polyspecific immune response in patients with MS.