[PubMed] [Google Scholar] 24. M23 was higher than binding to M1, including during relapses and remissions (< 0.0001), and the M23:M1 ratio was relatively constant within an individual patient. Titers usually fell after immunosuppression, but the titers at which relapses occurred varied markedly; no threshold level for relapses could be identified, and relapses could occur without a rise in titers. Relapse severity did not correlate with M23 or M1 antibody titers, although there was a correlation between the earliest M23 titers and annualized relapse rates. The M23:M1 ratio and absolute M23 and M1 titers did not relate to age at disease onset, ethnicity, disease severity, phenotype, or relapses at different anatomical sites. Conclusion: Relative AQP4 antibody binding to M23 and M1 isoforms differs between patients but there is no consistent association between these differences and clinical characteristics of disease. Nevertheless, the M23 isoform provided a slightly more sensitive substrate for AQP4-antibody assays, particularly for follow-up studies. Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disorder characterized by optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM). Limited phenotypes, known as NMO spectrum disorders (NMOSDs), are now recognized and include recurrent ON or, more commonly, monophasic or recurrent LETM. Antibodies to the water channel, aquaporin-4 (AQP4), are found in most patients, act as a disease biomarker, and are thought to be pathogenic.1,C4 AQP4 is expressed predominantly on astrocytes in 2 main forms. The AQP4 M23 isoform lacks a 22 amino acid intracellular N-terminus compared with the full-length AQP4 M1 isoform (hereafter M23 and M1). M23, but not M1, clusters at the cell surface to form orthogonal arrays of particles (OAPs) that appear to enhance antibody binding and complement Rabbit polyclonal to ZNF697 activation.5,6 NMOSD patient sera usually bind more strongly to the M23 isoform,7,C9 and there is a wide range of relative binding affinities for the 2 2 isoforms between patients.8 However, whether differences in Coenzyme Q10 (CoQ10) the specificity for the 2 2 isoforms are of clinical significance has not been systematically studied. We measured antibody binding to M1 and M23 isoforms expressed on human embryonic kidney (HEK) 293 cells in sera from 34 patients with clinically well-characterized NMO and NMOSD and related the findings to clinical features. METHODS Patients and sera. Clinical and serologic studies on patients seen by the UK National NMO specialist service were approved by the regional ethics committee and patients gave written consent. Sera from 34 patients with NMO/NMOSD were collected prospectively at outpatient visits and during relapses from September 2010 to September 2012 and stored at ?20C. Some patients also had sera stored from before September 2010. All patients had been Coenzyme Q10 (CoQ10) positive for AQP4 antibodies on at least 1 sample in routine clinical cell-based assays (CBAs) using the M23 isoform.10,11 Clinical data were collected prospectively at clinic visits and during hospital stays and stored anonymously in Coenzyme Q10 (CoQ10) a computerized database. Relapses were defined as the occurrence of new neurologic symptoms and signs and/or new MRI lesions. Relapse serum samples were taken within 14 days of relapse onset, with the exception of onset attack samples that were taken at first presentation to our service, within 3 months of the onset of neurologic symptoms. Remission samples had to be taken at least 28 days after the last relapse and more than 28 days before the next relapse. Ethics. Oxfordshire REC A (07/Q1604/28 Immune factors in neurological diseases) for the study of any patients whose samples have been referred for testing. Since January 2010, data on all patients seen within the Oxford clinical NMO service have been entered prospectively into a clinical database and patient serum samples routinely tested for AQP4 antibodies and myelin oligodendrocyte glycoprotein antibodies. Stable.