The Specificity of Anti- aquaporin-4 Antibodies for Neuromyelitis Optica Is Further Validated
The Specificity of Anti- aquaporin-4 Antibodies for Neuromyelitis Optica Is Further Validated
Abstract & Commentary
By Susan Gauthier, DO, MS, Assistant Professor of Neurology, Weill Cornell Medical College. Dr. Gauthier reports she receives research support from EMD Serono, Biogen-Idec, and Novartis Pharmaceuticals, and is on the speakers bureau for Biogen-Idec and Teva Neurosciences.
Synopsis: This study validated that anti-aquaporin-4 antibodies are highly specific (99.8%) for Devic's disease and related disorders when tested in a large series of miscellaneous autoimmune and non-autoimmune systemic diseases.
Source: Dellavance A, et al. Anti-aquaporin-4 antibodies in the context of assorted immune-mediated diseases. Eur J Neurol 2012;19:248-252.
The identification of anti-aquaporin-4 antibodies (NMO-IgG) has dramatically changed our approach to neuromyelitis optica (NMO) or Devic's disease, but the specificity of NMO-IgG for Devic's disease has been primarily derived from studies involving central nervous system (CNS) demyelinating diseases and healthy controls. The aim of this study by Dellavance et al was to determine if NMO-IgG could be detected in non-neurologic immune-mediated systemic diseases. The rationale for this study is based upon two important observations: 1) various neurological syndromes, including CNS demyelination, can occur in systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and Sjögren's disease (SS), and 2) other auto-antibodies (ANA, anti-SS-A/Ro, and anti-SS-B/La) can be present in patients with Devic's disease suggesting the presence of systemic autoimmunity.
In this study, sera from 673 patients with various clinical conditions were randomly selected from three different sources (a department of Neurology, a department of Rheumatology, and a large clinical laboratory) and were divided into five groups. The specimens from neurological diseases included Group I with 47 Devic's patients and Group II which consisted of patients with multiple sclerosis (MS, 13 pts), longitudinally extensive transverse myelitis (LETM, 17 pts), isolated recurrent optic neuritis (5 pts), and spinal cord inflammatory/vascular diseases (6 pts). The rheumatologic specimens were identified as Group III (220 pts) and included sera from patients with the following diseases: SLE, SS, rheumatoid arthritis, systemic sclerosis, primary biliary cirrhosis, and myasthenia gravis. Group IV (35 pts) included patients with either hepatitis C or other acute viral diseases. Lastly, Group V consisted of 300 specimens from miscellaneous diseases, which were randomly obtained from a clinical laboratory. NMO-IgG was detected in the following: 40/47 Devic's (85.1% sensitivity), 1/13 MS (7.7%), 10/17 (58.8%) LETM, and 3/5 (60%) of patients with isolated recurrent optic neuritis. NMO-IgG was not found in any of the other patient groups. The overall specificity of NMO-IgG for Devic's and related disorders (LETM and isolated recurrent optic neuritis) was calculated to be 99.8%. Neurological manifestations were present in 5/85 SLE and 5/15 SS patients.
Commentary
This study further validates anti-aquaporin-4 antibody as a specific marker for NMO or Devic's disease. The strength of this study lies in the large number of samples for which NMO-IgG was tested, but a flaw is the lack of clinical information in nearly half of the samples. Unfortunately, there were very few patients with neurological manifestations of a systemic autoimmune disease and having a larger cohort of these patients would have strengthened the findings. The specificity of NMO-IgG for Devic's disease (and related disorders) reported in this paper is in line with the known specificity from the original studies. NMO-IgG's target antigen is the aquaporin-4 water channel, in which titers have been found to correlate with NMO disease severity and treatment response; this suggests a direct relationship of the antibody to the pathogenesis of the disease.1 Through the development of this antibody, Devic's is no longer considered a clinical variant of MS but a distinct disease. Importantly, with the advent of this antibody, the spectrum of Devic's can be identified and treatment algorithms can be modified to target B-cell/antibody reduction as opposed to T-cell based therapies that are utilized to treat MS.
Reference
1. Takahashi T, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: A study on antibody titre. Brain 2007;130(Pt 5);1235-1243.
This study validated that anti-aquaporin-4 antibodies are highly specific (99.8%) for Devic's disease and related disorders when tested in a large series of miscellaneous autoimmune and non-autoimmune systemic diseases.Subscribe Now for Access
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