Extension of cytokines' role in Behcet's disease associated peripheral neuropathy

Behçet's disease (BD) is a chronic multisystem inflammatory disorder with diverse neurological manifestations. While central nervous system involvement is well recognized, peripheral neuropathy remains an underdiagnosed and poorly understood complication. Chemokines, particularly C-C motif chemokine ligand 21 (CCL21), play a critical role in immune-mediated neuroinflammation and have been implicated in several autoimmune diseases. This study aimed to investigate the association between selected CCL21 gene polymorphisms and BD-associated peripheral neuropathy, and to assess their relationship with disease activity.

This cross-sectional observational study included 42 adult patients with BD and 20 age- and sex-matched healthy controls. All patients underwent comprehensive clinical and neurological evaluation, assessment of disease activity, and nerve conduction studies. Genotyping of CCL21 single nucleotide polymorphisms rs951005, rs2492358, and rs2812378 were performed for patients and controls.

Electrophysiological evidence of peripheral neuropathy was detected in all evaluated Behçet's disease patients, despite only 50% reporting clinical neuropathic symptoms. Polyneuropathy was the predominant pattern, with sensory and mixed nerves more frequently affected than purely motor nerves, and greater involvement of upper limb nerves. A significant difference in the distribution of the CCL21 rs2492358 polymorphism was observed between patients and controls (p = 0.001). Additionally, the rs951005 polymorphism was significantly associated with higher disease activity scores (p = 0.009).

Peripheral neuropathy is a frequent and often subclinical manifestation of BD. CCL21 gene polymorphisms appear to contribute to both peripheral neuropathy association and disease activity, highlighting CCL21 as a potential biomarker linking systemic inflammation to peripheral nerve involvement. Key Points • Chemokine dysregulation previously found to play a central role in the development of neuroinflammation. • This cross-sectional study identifies specific chemokines' gene of CCL21 linked to peripheral neuropathy in Behcet's disease. • Results may guide future therapeutic strategies targeting chemokine modulation.