Aquaporin‐4 Antibodies (NMO‐IgG) as a Serological Marker of Neuromyelitis Optica: A Critical Review of the Literature

Abstract

Antibodies to aquaporin-4 (called NMO-IgG or AQP4-Ab) constitute a sensitive and highly specific serum marker of neuromyelitis optica (NMO) that can facilitate the differential diagnosis of NMO and classic multiple sclerosis. NMO-IgG/AQP4-Ab seropositive status has also important prognostic and therapeutic implications in patients with isolated longitudinally extensive myelitis (LETM) or optic neuritis (ON). In this article, we comprehensively review and critically appraise the existing literature on NMO-IgG/AQP4-Ab testing. All available immunoassays-including tissue-based (IHC), cell-based (ICC, FACS) and protein-based (RIPA, FIPA, ELISA, Western blotting) assays-and their differential advantages and disadvantages are discussed. Estimates for sensitivity, specificity, and positive and negative likelihood ratios are calculated for all published studies and accuracies of the various immunoassay techniques compared. Subgroup analyses are provided for NMO, LETM and ON, for relapsing vs. monophasic disease, and for various control groups (eg, MS vs. other controls). Numerous aspects of NMO-IgG/AQP4-Ab testing relevant for clinicians (eg, impact of antibody titers and longitudinal testing, indications for repeat testing, relevance of CSF testing and subclass analysis, NMO-IgG/AQP4-Ab in patients with rheumatic diseases) as well as technical aspects (eg, AQP4-M1 vs. AQP4-M23-based assays, intact AQP4 vs. peptide substrates, effect of storage conditions and freeze/thaw cycles) and pitfalls are discussed. Finally, recommendations for the clinical application of NMO-IgG/ AQP4-Ab serology are given.

Efficacy of glatiramer acetate in neuromyelitis optica spectrum disorder: a multicenter retrospective study

“…It should be considered that false-negative AQP4-IgG results cannot be completely ruled out given that some of the AQP4-IgG seronegative patients were treated with immunosuppressants at the time of testing. Treatment status and disease activity are known to influence the sensitivity of diagnostic tests for AQP4-IgG [32]. In patients with high suspicion of NMOSD, the AQP4-IgG serostatus should be investigated at regular intervals.…”

Crescentic glomerulonephritis in a patient with neuromyelitis optica (Devic´s syndrom)

“…Time and frequency of blood sampling seems to be another important confounder. Commonly patients are tested during onset of clinical symptoms or after initiation of therapy and thus may falsely appear seronegative for NMO autoantibodies [25] . Seronegative patients usually show no gender preference, but a higher proportion of monophasic courses of NMO and often a Caucasian descent [19] .…”

Biopsie bei tumorverdächtiger spinaler Raumforderung: Fallstrick Neuromyelitis optica

“…Für die NMO und ihre assoziierten Spektrumerkrankungen (s. u.; [1,37]) wurde vor wenigen Jahren ein hochspezifischer Immunglobulin-G(IgG)-Antikörper gegen den Aquaporin-4-Wasserkanal identifiziert, der sich überwiegend auf Astrozytenendfüßchen befindet. Dieser Antikörper differenziert die NMO von anderen entzündlichen Erkrankungen des ZNS, insbesondere der Multiplen Sklerose (MS; [12,18,21,22]). …”