Proprioceptive endings at muscle spindles as a possible target of autoantibodies

Autoimmune nodopathies are characterized by autoantibodies targeting proteins of the nodes of Ranvier of peripheral nerves. Anti-Contactin-1 (CNTN1) autoantibodies are associated with sensorimotor neuropathy and severe sensory ataxia. While damage to the nodal architecture due to axoglial disjunction is considered the primary pathogenic mechanism of autoimmune nodopathies, the reason for the severe sensory ataxia, accompanied by proprioceptive impairment, remains unclear. We therefore aimed to investigate the expression of CNTN1 in muscle spindles and the binding of IgG from patients with anti-CNTN1 and other paranodal/nodal autoantibodies to these structures. Using immunofluorescence staining of murine muscle tissue, we demonstrate that CNTN1 is expressed in annulospiral fibers of muscle spindles. IgG from patients with anti-CNTN1 autoantibodies showed specific binding to these structures, whereas IgG of patients with other paranodal autoantibodies did not. Additionally, IgG from a subset of patients with autoimmune neuropathy and severe sensory ataxia that were negatively tested for paranodal autoantibodies showed distinct binding to annulospiral fibers. Our findings suggest that CNTN1 might play a role in proprioceptive signal transmission at annulospiral fibers and autoantibody-mediated dysfunction at annulospiral fibers may contribute to severe sensory ataxia. These results highlight annulospiral fibers as potential targets for future research on autoantibody-mediated neuropathies.