Murat Giriş1, Sinem Bireller2, Cem İsmail Küçükali1, Haşmet Hanağasi3, Sevgin Değirmencioğlu1, Erdem Tüzün1. 1. Department of Neuroscience, Aziz Sancar Institute of Experimental Medical Research, İstanbul University, İstanbul, Turkey. 2. Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medical Research, İstanbul University, İstanbul, Turkey. 3. Department of Neurology, İstanbul University School of Medicine, İstanbul, Turkey.
Abstract
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.
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.
Entities:
Keywords:
Behçet disease; immunoglobulin G; neuro-Behçet disease; neurotoxicity; terminal deoxynucleotidyl transferase dUTP nick end labeling
Authors: B Taşçi; H Direskeneli; P Serdaroglu; G Akman-Demir; M Eraksoy; G Saruhan-Direskeneli Journal: Clin Exp Immunol Date: 1998-07 Impact factor: 4.330