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International Association for the Study of Pain

Internalisation of CASPR2 autoantibodies in peripheral sensory neurons - Plenary Hall

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Abstract Description

Institution: Univeristy of Oxford - Oxfordshire, United Kingdom

Contactin-associated protein-like 2 (CASPR2) and leucine-rich glioma inactivated 1 (LGI-1) are proteins part of the voltage-gated potassium channel (VGKC) complex known to be the target of autoantibodies in neuropathic pain patients. Pain has been reported as a common clinical symptom in patients with LGI1 and CASPR2 autoantibodies. Treatment of patients with immunotherapies showed improvements in their pain, suggesting that autoantibodies may be causative of pain. Furthermore, the passive transfer of neuropathic patient IgG in mice resulted in pain-related hypersensitivity, confirming the pathogenicity of autoantibodies in vivo. There are currently few studies characterising the binding and mechanisms of patient sera on peripheral sensory neurons. Hence, the pathophysiology of autoantibody-mediated pain is still not well-understood. We assess sera from patients with or without neuropathic pain for binding and internalisation in rodent dorsal root ganglia (DRG) neurons. Here, we explore internalisation as a putative pathogenic mechanism of autoantibodies on periphery sensory neurons that- to the best of our knowledge- has not yet been described. We demonstrate that patient autoantibodies internalise in rodent DRG neurons in an antigen-specific manner and show that the internalisation assay can be applied in investigating autoantibody-mediated pain conditions to strengthen clinical-serological correlations.  

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Authors

Internalisation of CASPR2 and LGI1 autoantibodies in peripheral sensory neurons Mandy Tseng - University of Oxford

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