Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese

• Published in: Multiple sclerosis 2009-07, Vol.15 (7), p.834-847
• Main Authors: Matsushita, T, Isobe, N, Matsuoka, T, Shi, N, Kawano, Y, Wu, XM, Yoshiura, T, Nakao, Y, Ishizu, T, Kira, JI
• Format: Article
• Language: English
• Subjects: Aquaporin 4 - immunology; Asian Continental Ancestry Group; Autoantibodies - blood; Biological and medical sciences; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Humans; Immunoglobulin G - blood; Interferon-gamma - blood; Interleukin-4 - blood; Japan; Magnetic Resonance Imaging; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Chronic Progressive - ethnology; Multiple Sclerosis, Chronic Progressive - immunology; Multiple Sclerosis, Chronic Progressive - pathology; Multiple Sclerosis, Relapsing-Remitting - ethnology; Multiple Sclerosis, Relapsing-Remitting - immunology; Multiple Sclerosis, Relapsing-Remitting - pathology; Neurology; Neuromyelitis Optica - ethnology; Neuromyelitis Optica - immunology; Neuromyelitis Optica - pathology; Optic Neuritis - ethnology; Optic Neuritis - immunology; Optic Neuritis - pathology; Predictive Value of Tests; Reproducibility of Results; Spinal Cord - pathology; Syndrome
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458509104595

Background Antibodies to aquaporin-4 (AQP4) are found in a fraction of Japanese opticospinal multiple sclerosis (OSMS) patients. However, it remains unknown whether anti-AQP4 antibody-positive and negative OSMS patients possess an identical disease. Objective The objective of the current study was to clarify immunological differences between the two groups of patients. Methods We studied the serum antibody titers against AQP4 in 191 patients with idiopathic central nervous system demyelinating diseases and clarified their relationships with immunological parameters. Results Anti-AQP4 antibody positivity rate was higher in patients with OSMS (21/58, 36.2%), idiopathic recurrent myelitis (4/17, 23.5%), and recurrent optic neuritis (7/26, 26.9%), than in conventional MS (CMS) patients (6/90, 6.7%) and patients with other diseases (0/87). Anti-AQP4 antibody titer was significantly higher in patients with SS-A/B antibodies than in those without them. Anti-AQP4 antibody-negative OSMS patients showed significantly higher CD4+IFN-γ+IL-4−T cell percentages and intracellular IFN-γ/IL-4 ratios than anti-AQP4 antibody-positive patients, anti-AQP4 antibody-negative CMS patients, and healthy controls, and CD4+IFN-γ+IL-4−T cell percentages were negatively correlated with anti-AQP4 antibody titers. Conclusion Anti-AQP4 antibody-positive patients are immunologically distinct from anti-AQP4 antibody-negative OSMS patients owing to a Th2 shift in the former group in comparison to a Th1 shift in the latter.