Exploring the Role of Nuclear Factor Kappa B in the Immunobiology of Inflammatory Neuropathies

探索核因子κB在炎症性神经病免疫生物学中的作用

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Abstract

BACKGROUND AND OBJECTIVES: Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are inflammatory conditions, representing prototype examples of immune-mediated disorders of the peripheral nervous system. Activation of the nuclear factor-κB (NF-κB) pathway is crucial for generating immune and inflammatory responses and creating an inflammatory milieu; however, this has not been studied in inflammatory neuropathies. We aimed to quantify the expression levels of two critical genes in the NF-κB pathway ( Nfkb1 and Nfkb2 ), together with a prototype inflammatory gene, Tnfα , in inflammatory neuropathies. METHODS: Forty-nine patients with inflammatory neuropathies (GBS = 38, CIDP = 11) were recruited prospectively from a single neurology unit. Gene expression levels of Nf κ b1 , Nf κ b2 , and Tnfα were quantified using quantitative real-time polymerase chain reaction. RESULTS: There were significantly increased expression levels of Nf κ b1 in the inflammatory neuropathy group compared to healthy controls ( P = 0.001), GBS versus healthy controls ( P = 0.03), and CIDP versus healthy controls ( P = 0.003). There were no significant differences in the expression levels of Nf κ b2 and Tnfα genes between cases and controls. There was no correlation between the expression levels of these genes and the clinical severity scores. CONCLUSIONS: The present study provides evidence for NF-κB pathway activation in inflammatory neuropathies, including both GBS and CIDP, suggesting that this spectrum of disorders may share a common central pathway for immune activation. Thus, the NF-κB pathway plays a critical role in the immunopathogenesis of inflammatory neuropathies; however, the molecular interacting partners within the immune system need to be studied to identify the differential immune trajectories in GBS and CIDP.

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