N-Methyl-D-Aspartate Receptor Antibodies in Neuroinflammatory Diseases

Antibodies against N-methyl-D-aspartate receptors (NMDAR) are found in sera and cerebrospinal fluid of patients with NMDAR encephalitis. Detection of these autoantibodies is currently the most specific method to support the diagnosis of the disease. An association of NMDAR antibodies with other neuroinflammatory diseases, such as multiple sclerosis, neuromyelitis optica spectrum disorders, and neuropsychiatric systemic lupus erythematosus, has been speculated. In the current study we developed a live cell based assay to detect and quantify NMDAR antibodies through their binding to native, human NMDAR expressed in HEK293A cells. Sera of eight patients with known NMDAR encephalitis, which have previously been identified by a commercially available diagnostic test, were positive for NMDAR antibodies in our live cell based assay. In one patient the change of antibody titer during disease progression and ongoing therapy was determined. As controls, we used 46 patients with non-inflammatory neurological diseases and 49 healthy controls, which were all negative for NMDAR. Our analysis of patients with neuroinflammatory diseases shows no presence of NMDAR antibodies in clinically isolated syndrome (15), multiple sclerosis (59), neuromyelitis optica (7), acute disseminated encephalomyelitis (40), systemic lupus erythematosus (27), and other neuroinflammatory diseases (13). Currently, we are establishing a flow cytometry based assay as an alternative method for antibody testing and quantification. In addition, we plan to use the live cell based assay to investigate biological effects of patient's antibodies on NMDAR which would contribute to a better understanding of the pathogenesis of NMDAR encephalitis.

Melanie Ramberger is enrolled in the graduate program SPIN supported by the Austrian Research Foundation (FWF DK W1206).