Journal article

Publication year: 2016

Pages: 2617-2630

Journal: Brain

Volume number: 139

ISSN: 0006-8950

eISSN: 1460-2156

Open access status: Bronze

DOI Link: https://doi.org/10.1093/brain/aww189

Publisher: Oxford University Press

Abstract: 
The myelin sheath is connected to the axon at paranodes by a protein complex comprising neurofascin-155, contactin-1 and Caspr. Doppler et al. report a new subtype of antibody-associated neuropathy, in which autoantibodies against Caspr give rise to a painful sensorimotor neuropathy with an excellent response to rituximab.The myelin sheath is connected to the axon at paranodes by a protein complex comprising neurofascin-155, contactin-1 and Caspr. Doppler et al. report a new subtype of antibody-associated neuropathy, in which autoantibodies against Caspr give rise to a painful sensorimotor neuropathy with an excellent response to rituximab.Auto-antibodies against the paranodal proteins neurofascin-155 and contactin-1 have recently been described in patients with chronic inflammatory demyelinating polyradiculoneuropathy and are associated with a distinct clinical phenotype and response to treatment. Contactin-associated protein 1 (Caspr, encoded by CNTNAP1) is a paranodal protein that is attached to neurofascin-155 and contactin-1 (CNTN1) but has not yet been identified as a sole antigen in patients with inflammatory neuropathies. In the present study, we screened a cohort of 35 patients with chronic inflammatory demyelinating polyradiculoneuropathy (age range 20-80, 10 female, 25 male) and 22 patients with Guillain-Barr, syndrome (age range 17-86, eight female, 14 male) for autoantibodies against paranodal antigens. We identified two patients, one with chronic inflammatory demyelinating polyradiculoneuropathy and one with Guillain-Barr, syndrome, with autoantibodies against Caspr by binding assays using Caspr transfected human embryonic kidney cells and murine teased fibres. IgG3 was the predominant autoantibody subclass in the patient with Guillain-Barr, syndrome, IgG4 was predominant in the patient with chronic inflammatory demyelinating polyradiculoneuropathy. Accordingly, complement deposition after binding to HEK293 cells was detectable in the patient with IgG3 autoantibodies only, not in the patient with IgG4. Severe disruption of the paranodal and nodal architecture was detectable in teased fibres of the sural nerve biopsy and in dermal myelinated fibres, supporting the notion of the paranodes being the site of pathology. Deposition of IgG at the paranodes was detected in teased fibre preparations of the sural nerve, further supporting the pathogenicity of anti-Caspr autoantibodies. Pain was one of the predominant findings in both patients, possibly reflected by binding of patients' IgG to TRPV1 immunoreactive dorsal root ganglia neurons. Our results demonstrate that the paranodal protein Caspr constitutes a new antigen that leads to autoantibody generation as part of the novel entity of neuropathies associated with autoantibodies against paranodal proteins.

Harvard Citation style: Doppler, K., Appeltshauser, L., Villmann, C., Martin, C., Peles, E., Kraemer, H., et al. (2016) Auto-antibodies to contactin-associated protein 1 (Caspr) in two patients with painful inflammatory neuropathy, Brain, 139, pp. 2617-2630. https://doi.org/10.1093/brain/aww189

APA Citation style: Doppler, K., Appeltshauser, L., Villmann, C., Martin, C., Peles, E., Kraemer, H., Haarmann, A., Buttmann, M., & Sommer, C. (2016). Auto-antibodies to contactin-associated protein 1 (Caspr) in two patients with painful inflammatory neuropathy. Brain. 139, 2617-2630. https://doi.org/10.1093/brain/aww189