Serum Immunoglobulin G of Neuro-Behçet’s Disease Patients Reduce Cerebral Expression Levels of Survival Pathway Factors
Küçükali, Cem İsmail
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Objective: Anti-neuronal antibodies are found in sera of neuro-Behçet’sdisease (NBD) patients. In this study, our aim was to analyze the potentialmechanisms by which NBD immunoglobulin (Ig) Gs affect neuronaldysfunction. Materials and Methods: Purified IgGs obtained from pooledsera of six each NBD patients and healthy controls (HCs) were administeredto Sprague Dawley rats through intraventricular injection. Control rats receivedphosphate-buffered saline (PBS) only. Locomotor activity was assessed byopen field test on days 0, 10, and 25. Cerebral expression levels of intracellularpathway factors associated with cell survival and viability were measured byreal-time polymerase chain reaction. Results: Rats treated with NBD IgGexhibited reduced motor activity. On day 25, the mean number of crossings was44 ± 7, 90 ± 12, and 93 ± 5 and the mean number of rearings was 18 ± 7,34 ± 5, and 35 ± 6 for NBD IgG, HC IgG, and PBS groups, respectively(P < 0.001). Relative expression levels of Akt-1 (0.4 ± 0.2, 1.0 ± 0.3, and0.9 ± 0.6; P = 0.004), DJ-1 (0.6 ± 0.2, 1.0 ± 0.6, and 0.9 ± 0.5; P = 0.047),mouse double mininute-2 (0.5 ± 0.3, 0.9 ± 0.2, and 1.0 ± 0.2; P = 0.002), andmechanistic target of rapamycin (0.4 ± 0.2, 0.8 ± 0.4, and 0.9 ± 0.6; P = 0.006)were significantly lower in NBD-IgG group than HC IgG and PBS groups. Bycontrast, the expression levels of factors associated with apoptosis (caspase 3,mitochondrial carrier homolog 1, and B-cell lymphoma-2) were comparableamong different treatment arms. Conclusion: Our results suggest that at least afraction of NBD IgG interacts with neuronal surface antigens and subsequentlydecreases neuronal viability through Akt pathway inhibition. By contrast, NBDIgG does not appear to activate neuronal apoptosis. Further identification of thebinding sites of serum IgG ıs required.
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