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NMO-IgG diagnostic and prognostic performance

Background: NMO-IgG, a serum IgG which reacts with aquaporin-4 (AQP4), is a specific biomarker for neuromyelitis optica (NMO) and related disorders. It was reported in 2004 by Mayo Clinic investigators and several independent teams have studied the performance characteristics of new assays for AQP4...

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Bibliographic Details
Published in:Multiple sclerosis 2008-09, Vol.14, p.S292-S292
Main Authors: Matiello, M, Weinshenker, B
Format: Article
Language:English
Online Access:Get full text
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Summary:Background: NMO-IgG, a serum IgG which reacts with aquaporin-4 (AQP4), is a specific biomarker for neuromyelitis optica (NMO) and related disorders. It was reported in 2004 by Mayo Clinic investigators and several independent teams have studied the performance characteristics of new assays for AQP4 antibodies. The studies have varied in the selection of cases (NMO, opticospinal multiple sclerosis (OSMS), limited/inaugural forms-Iongitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis(RON)); controls (multiple sclerosis (MS), other neurological or autoimmune disease) and in immunoassay technique. Objective: To summarize data on assays that detect AQP4-speciflc antibody according to case and control selection and immunoassay technique. Methods: We carried out a systematic review of the indexed literature from 2004 to 2008. Results: Eleven case-controls and two longitudinal studies of seropositive inaugural syndromes were reviewed. In total 1475 individuals were tested for NMO-IgG combining the case-control studies: 305 NMO cases, 140 limited syndromes suggestive of NMO and 1030 controls. When compared with MS controls, the specificity ranged between 85% and 100%. The sensitivity range was 47% to 91%. The sensitivity was lower when OSMS (LETM not required) was used as the case definition or when studying children. Sensitivity and specificity for isolated or recurrent LETM was only slightly lower than for NMO. Immunoassays included indirect immunofluorescence (IF) with rodent central nervous system (CNS) substrate, indirect IF on cells stably transfected with AQP4-CDNA and radio-immunoprecipitation assay using recombinant AQP4. The sensitivity and specificity did not differ importantly between assay techniques, although conflicting results by two groups were reported when the reference IF assay on mouse brain at Mayo Clinic was compared directly with IF on transfected cell lines. For patients with a single episode of LETM and with RON, seropositivity for NMO-IgG predicted recurrence of LETM and ON. Conclusions: NMO-IgG is highly specific for the diagnosis of NMO and related disorders, and predicts the risk of recurrence of myelitis and/or ON in patients with limited or inaugural presentations of NMO. Superiority of one immunoassay technique has not been demonstrated, so further study is required.
ISSN:1352-4585