Polyspecific, antiviral immune response distinguishes multiple sclerosis and neuromyelitis optica

Abstract

Background: A polyspecific, intrathecal humoral immune response against neurotropic viruses such as measles, rubella and varicella zoster virus (MRZ reaction, MRZR) is present in 80-100% of patients with multiple sclerosis (MS), but has not to date been evaluated in patients with neuromyelitis optica (NMO). Aims: To evaluate whether MRZR distinguishes NMO and MS. Methods: 20 patients with NMO and 42 with MS were included. The intrathecal synthesis of antibodies against measles, rubella and varicella zoster virus was detected by calculation of the respective antibody indices (AI). Results: A positive MRZ reaction, as defined by a combination of at least two positive AIs, was found in 37/ 42 MS, but in only 1/20 NMO patients (p,0.0001).Median AI values differed significantly between the groups (p,0.0005). Conclusions: The polyspecific antiviral humoral immune response characteristic for MS is widely missing in NMO, irrespective of the NMO-IgG status of the patients. Our findings further strengthen the case for NMO being pathologically distinct from MS.Neuromyelitis optica (NMO, Devic syndrome) is a severe inflammatory disorder of the CNS of putative autoimmune aetiology, predominantly affecting the spinal cord and optic nerves. 1Whether NMO is distinct from multiple sclerosis (MS) or rather a variant of MS is currently under discussion.2 3 To further elucidate this question, we compared the antiviral, intrathecal antibody repertoire in MS and NMO. MS is well known to be characterised by a polyspecific, intrathecal B cell response against neurotropic viruses such as measles, rubella and varicella zoster virus (MRZ reaction, MRZR), which is detectable in 80-100% of patients with MS. [4][5][6][7][8][9] In this study, we investigated whether such a reaction is also present in NMO, and whether it might help to distinguish between NMO and MS. ) were detectable in 7/20 patients (35%; 4/7 NMO-IgG positive) during the course of disease. NMO followed a relapsing course in 18 patients and was monophasic in two. Median follow-up was 39 months (range 11-288). Serum and CSF samples were obtained 0-286 months from first myelitis (median 2 months; ,6 months in nine patients; .24 months in four) and 0-282 months from first optic neuritis (median 11 months; ,6 months in nine patients; .24 month in seven). As a control group, MRZR results from 42 consecutive patients with MS (28 with myelitis) from Germany were analysed, including 29 patients with relapsingremitting MS (RRMS), four patients with secondary progressive MS (SPMS) and nine patients with a clinically isolated syndrome suggestive of MS (CIS) at the time of lumbar puncture. Diagnosis of MS was established according to McDonald and colleagues. 12 The sex distribution was 1:3.2 (10 men, 32 women). Median age was 34.5 years (range 18-62). Serum and CSF samples were collected 0-294 months from first relapse (median 13 months; ,6 months in 17 patients; .24 months in 15). All lumbar punctures were performed for diagnostic purposes only. PATIENTS AND METHODSQuantita...

Cerebrospinal fluid/serum gradient of IgG is associated with disability at acute attacks of neuromyelitis optica

“…However, though mere increased BBB disruption has been previously found in patients with NMO [4], its association with disability at acute relapse has not been proved clinically. The aim of this study was to determine whether increased BBB permeability and/or a subsequent high cerebrospinal fluid (CSF)-blood gradient of IgG is associated with disease activity in NMO.…”

EBV in MS: guilty by association?

“…within the spinal canal) synthesis of antibodies (i.e. antibodies are not passively diffusing into the CSF but are produced within the CSF compartment) against a variety of viruses including measles, rubella, varicella zoster virus and the human herpesvirus 6 [26][27][28][29][30]. Despite many claims that a transmissible agent was found specifically in the brains of MS patients and despite reports of diseasespecific higher antibody titers to various viral and bacterial candidates (including EBV), a specific infectious agent has so far not been linked convincingly to MS.…”

Glial and Axonal Pathology in Multiple Sclerosis

“…This hypothesis has been supported by the reports showing that more than 80% of people with MS display humoral intrathecal response against neurotrophic viruses (herpes simplex, measles, rubella and varicela zoster, among others). The combined response against these neurotrophic viruses in the CNS of MS patients, was coined by Reiber et al as MRZ reaction, and many others groups have disagreed on the diagnostic value of this detection from CSF analysis in more than 90% of MS patients Colleen et al, Correales, 2004;Jarius, 2008, Jarius et al, 2009Luchinetti, 2007, since a similar frequency of this autoimmune chronic reaction was observed in other neurological diseases Jarius, 2008; Jarius et al, 2009. The MRZ reaction has also been reported in NMO patients, although in a lower frequency than in MS, and it has been useful to establish a differential diagnosis between both demyelinating diseases Jarius, 2008.…”