Autoantibodies against contactin‐associated protein 1 and complexes of paranode‐specific proteins in chronic inflammatory demyelinating polyradiculoneuropathy

Objective To investigate the frequency of serum autoantibodies targeting contactin‐associated protein 1 (Caspr1) and its complexes with other paranode antigens, contactin‐1 (CNTN1) and neurofascin 155 (NF155), in Japanese patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods Sera from 26 CIDP patients, 35 patients with Guillain–Barré syndrome, and 31 healthy individuals participated. Paranodal immunoglobulin G antibodies were quantified using enzyme‐linked immunosorbent assays with commercially available recombinant proteins as antigens. Results Anti‐Caspr1 antibodies were present in one participant (case 1, 3.8%) of CIDP, and negative in all Guillain–Barré syndrome patients and healthy participant. Case 1 was a man who developed subacute distal limb‐predominant muscle weakness and sensory ataxia with postural hand tremor at 69 years‐of‐age, and therapeutic benefit of intravenous immunoglobulin and oral steroids was inadequate. The detected anti‐Caspr1 antibodies predominantly belonged to the immunoglobulin G4 subclass, and the addition of CNTN1 to Caspr1 as an antigen increased antibody reactivity, although the increase was just 20–30% at most. The presence of autoantibodies against paranode protein complexes, including Caspr1/CNTN1, Caspr1/NF155 and Caspr1/CNTN1/NF155, was confirmed in several CIDP patients, although they also had anti‐Caspr1 or anti‐NF155 antibodies; thus, in our cohort, there were no patients with autoantibodies that specifically recognized paranode protein complexes. Conclusions This is the first confirmed Japanese case of anti‐Caspr1 antibody‐positive CIDP with a clinical signature similar to that of patients of Western origin. Our preliminary study did not identify the presence of specific antibodies against the paranode protein complexes, and the primary target antigen is likely Caspr1. The first Japanese case of anti‐contactin‐associated protein 1 antibody‐positive chronic inflammatory demyelinating polyradiculoneuropathy showed similar clinical pictures to cases reported from Western countries, including enlargement of the nerve roots with gadolinium contrast effect.