Introduction: Parenchymal neuro-Behçet disease (NBD) is encountered in 5%-15% of Behçet disease (BD) patients and is characterized by inflammation of the brainstem and diencephalon structures. Neuronal apoptosis has been shown to participate in neuronal cell loss. Anti-neuronal antibodies have been identified in NBD patients. However, the pathogenic properties of these antibodies have not been studied. Methods: To delineate the potential pathogenic activity of serum antibodies on neurons, pooled sera from seven NBD patients and seven healthy controls were divided into purified immunoglobulin G (IgG) and IgG-depleted serum fractions, and each fraction was administered to cultured SH-SY5Y neuroblastoma cells. Cell death was evaluated with a toxicity assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Moreover, expression levels of several apoptosis markers were evaluated with real time polymerase chain reaction (PCR). Results: Administration of NBD IgG to cultured SH-SY5Y cells induced significantly increased cell death and apoptosis compared with other treatments. NBD IgG also enhanced the mRNA expression levels of major apoptosis and cell survival pathway factors. Conclusion: Our results suggest that IgGs isolated from the sera of NBD patients have a neurotoxic activity that is presumably mediated by apoptotic mechanisms. [ABSTRACT FROM AUTHOR]