Marzena J Fabis-Pedrini1, Christine Bundell2, Chee-Keong Wee1, Michaela Lucas3, Andrew McLean-Tooke4, Frank L Mastaglia1, William M Carroll5, Allan G Kermode6. 1. Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perron Institute for Neurological & Translational Science, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia. 2. PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia, Australia. 3. PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia; School of Medicine and Pharmacology, School of Pathology and Laboratory Medicine, UWA, Perth, Western Australia, Australia; Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia; Department of Immunology, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia. 4. PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia; Department of Immunology, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia. 5. Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perron Institute for Neurological & Translational Science, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia; Department of Neurology & Clinical Neurophysiology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. 6. Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perron Institute for Neurological & Translational Science, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia; Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia; Department of Neurology & Clinical Neurophysiology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. Electronic address: allan.kermode@uwa.edu.au.
Abstract
OBJECTIVE: To evaluate the prevalence of anti-AQP4 antibody in serum and CSF samples from patients being investigated for possible neuromyelitis optica spectrum disorder (NMOSD) referred to the PathWest State reference laboratory using a sensitive cell-based assay (CBA). BACKGROUND: NMOSD is an inflammatory CNS disease distinct from MS, which is relatively rare in Western countries. A proportion of patients with NMOSD have detectable serum IgG antibodies that target the water channel aquaporin-4 (AQP4-IgG), but the frequency varies in different populations studied and according to the assay method employed. METHODS: Sera or CSF from a diagnostic cohort of 196 consecutive patients with possible NMOSD which had previously been screened by indirect immunofluorescence (IIF) on primate cerebellum were re-tested for AQP4-IgG reactivity to the M1 and M23 isoforms of AQP4 using a commercial CBA. A control group of 205 patients with definite MS was also included in the study. RESULTS: Of the 196 patients, only 5 sera were AQP4-IgG positive, representing 2.6% of patients in the diagnostic cohort. All 5 AQP4-IgG positive patients fulfilled the 2015 revised diagnostic criteria for NMOSD and were females of varied ethnic origins, 4 of whom had longitudinally extensive transverse myelitis. The CBA confirmed AQP4-IgG positivity in the four patients previously reported as positive by IIF, and an additional patient with NMOSD who had previously been diagnosed as MS was also identified. None of the 205 MS sera were AQP4-IgG positive. CONCLUSIONS: Our study confirms the utility and greater reliability of the M1/M23 CBA for detecting AQP4-IgG in patients with possible NMOSD, and indicates a prevalence of seropositive NMOSD in the Western Australian population similar to that in other Western populations.
OBJECTIVE: To evaluate the prevalence of anti-AQP4 antibody in serum and CSF samples from patients being investigated for possible neuromyelitis optica spectrum disorder (NMOSD) referred to the PathWest State reference laboratory using a sensitive cell-based assay (CBA). BACKGROUND: NMOSD is an inflammatory CNS disease distinct from MS, which is relatively rare in Western countries. A proportion of patients with NMOSD have detectable serum IgG antibodies that target the water channel aquaporin-4 (AQP4-IgG), but the frequency varies in different populations studied and according to the assay method employed. METHODS: Sera or CSF from a diagnostic cohort of 196 consecutive patients with possible NMOSD which had previously been screened by indirect immunofluorescence (IIF) on primate cerebellum were re-tested for AQP4-IgG reactivity to the M1 and M23 isoforms of AQP4 using a commercial CBA. A control group of 205 patients with definite MS was also included in the study. RESULTS: Of the 196 patients, only 5 sera were AQP4-IgG positive, representing 2.6% of patients in the diagnostic cohort. All 5 AQP4-IgG positive patients fulfilled the 2015 revised diagnostic criteria for NMOSD and were females of varied ethnic origins, 4 of whom had longitudinally extensive transverse myelitis. The CBA confirmed AQP4-IgG positivity in the four patients previously reported as positive by IIF, and an additional patient with NMOSD who had previously been diagnosed as MS was also identified. None of the 205 MS sera were AQP4-IgG positive. CONCLUSIONS: Our study confirms the utility and greater reliability of the M1/M23 CBA for detecting AQP4-IgG in patients with possible NMOSD, and indicates a prevalence of seropositive NMOSD in the Western Australian population similar to that in other Western populations.
Authors: Kerri Prain; Mark Woodhall; Angela Vincent; Sudarshini Ramanathan; Michael H Barnett; Christine S Bundell; John D E Parratt; Roger A Silvestrini; Wajih Bukhari; Fabienne Brilot; Patrick Waters; Simon A Broadley Journal: Front Neurol Date: 2019-10-04 Impact factor: 4.003