Anti-Glutamate Receptor Epsilon 2 Autoantibodies in Patients with Creutzfeldt-Jakob Disease (S57.002)

Abstract

Objective: We investigated the association of Creutzfeldt-Jakob disease (CJD) and antibodies against NMDA-type glutamate receptor e2 (GluRe2, also called as NR2B or GluN2B). Background CJD is not completely related to immunological responses. However, immune abnormalities such as elevated pro- and anti-inflammatory cytokines have been reported in patients with CJD, warranting investigation of the immunological aspects of this disease. Furthemore, the clinical features of CJD can resemble those of autoimmune limbic encephalitis with autoantibodies, such as antibodies against GluRe2. Design/Methods: Thirteen patients who met the World Health Organization criteria for CJD and were admitted to our hospitals between January 2004 and December 2010 were enrolled in this study. Patients with autoimmune limbic encephalitis were enrolled as disease controls. We performed immunohistochemical analysis using rat brain and polyclonal anti-GluRe2 IgG to examine whether the sera from patients with CJD contained antibodies to GluRe2. Then, we measured the titers of antibodies against the extracellular or intracellular domains of GluRe2 in the sera or CSF using a conventional enzyme-linked immunosorbent assay. We compared the titers of the antibodies among the control, limbic encephalitis, and CJD cases. Results: Patients9 sera reacted with neural components of the rat hippocampus, and the reactivity corresponded to GluRe2 expression. The titers of anti-GluRe2 antibodies were elevated significantly in the sera and CSF of CJD patients. There were trends toward higher values in CJD than in encephalitis, although the differences were not significant. Conclusions: We detected antibodies to NMDA-type GluRe2 in patients with CJD. Our results facilitate the recognition of immune responses in CJD, and suggested a partly shared pathomechanism between CJD and autoimmune encephalitis. Supported by: Grants-in-Aid from the Research Committee of Prion Disease and Slow Virus Infection, the Ministry of Health, Labour and Welfare of Japan; Health and Labour Sciences Research Grants for Research on Psychiatry and Neurological Diseases and Mental Health. Disclosure: Dr. Fujita has nothing to disclose. Dr. Yuasa has nothing to disclose. Dr. Takahashi has nothing to disclose. Dr. Sako has nothing to disclose. Dr. Izumi has nothing to disclose. Dr. Kaji has nothing to disclose.