The Activation of Rage and Nf-Kb in Nerve Biopsies of Patients with Axonal and Vasculitic Neuropathy
Bekircan-Kurt, Can Ebru
Ozdamar, Sevim Erdem
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Introduction: The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor expressed in tissues and cells, which plays a role in immunity. The activation of RAGE results in the translocation of nuclear factor kappa B (NF-kappa B) to the nucleus for expression of proinflammatory molecules. The role of the RAGE pathway in the pathogenesis of diabetic complications is well determined. We aimed to investigate the role of the RAGE pathway in axonal and vasculitic neuropathy. Methods: We immunoreacted nerve biopsy samples from 17 axonal neuropathy (AN), 11 vasculitic neuropathy (VN) and 12 hereditary neuropathy (as a control group) with liability to pressure palsy (HNPP) patients with antibodies to NF-kappa B and RAGE. Subsequently, we performed double staining with the antibodies to NF-kappa B or RAGE and T cells, macrophages and Schwann cells. Results: RAGE and NF-kappa B immunoreactivities were higher in the perivascular cuff and in endoneurial cells in VN than in AN and HNPP. Although there is no significant difference, nerve biopsies with AN showed higher NF-kappa B and RAGE immunoreactivities than HNPP. The colocalization study showed that most of the NF-kappa B- and RAGE-positive cells were CD8 (+) T cells in VN. In AN, all NF-kappa B- and RAGE-positive cells were macrophages, whereas all NF-kappa B-and RAGE-positive cells were Schwann cells in HNPP. Conclusion: The activation of the RAGE pathway predominant in CD8 (+) T cells underscores its role in VN. In AN patients, the immunoreactivity to NF-kappa B and RAGE in macrophages may support their role in axonal degeneration without inflammatory milieu.