Analysis of auto-antibodies in psychotic disorder

OBJECTIVES: Antibodies against neuronal antigens such as N-methyl-D-aspartate receptor (NMDAr), and voltage gated potassium channel (VGKC) complexare present in various CNS excitability disorders, including cerebellar ataxia, encephalitis and epilepsy. Recently, an increasing number of reports indicatethat these types of antibodies are also seen in a subgroup of psychotic disorder patients. Yet, results of different research groups are inconsistent.We aimed to identify the presence of pathogenic autoantibodies targeting NMDAr and VGKC in sera of psychotic disorder and healthy individuals. METHODS: We analyzed the presence of NMDAr-autoantibodies of the IgG isotype in sera of 230 psychotic disorder patients and 293 controls. To this end we made use of an in-house cell based assay with HEK293 cells expressing GluN1 and GluN2B subunit of NMDAr. 120 schizophrenia patient sera were additionally screened for the presence of VGKC antibodies usingradio immuno assay (RIA) from DLDDiagnostika GmbH. Sera tested positive by RIA were subsequently retested with rat brain immunohistochemistry (IHC) and on cell based assay (CBA) of transfected HEK293 cells for the VGKC complex proteins leucine-rich glioma inactivated-1 (LGI-1) and contactin-associated protein-like 2 (CASPR2). RESULTS: No antibodies against the Nr1 subunit of the NMDAr were found in the sera of patients and controls. 4 patients were positive (>100 pmol/l) and 2 borderline positive (>50 pmol/l) for VGKC complex autoantibodies when tested by RIA. None of the positive screened sera could be confirmed as positive on rat brain IHC or CBA for CASPR2 and LGI-1. CONCLUSION: The results indicate that the presence of NMDAr-autoantibodies against Nr1 in the sera of patients with psychotic disorder is rare. Yet, we cannot rule out that these antibodies can only be detected in the cerebrospinal fluid of these patients.Autoantibodies against VGKC complex might be present in a small population of psychotic disorder patients. It has to be further investigated whether the indirect immunofluorescence is sensitive enough to detect autoantibodies in the serum or if the RIA could give false positive results.For a reliable diagnosis of patients it will be essential to improve the selectivity of the antibody detection assays as a solid basis for adequate immunosuppressive therapy.status: publishe