Characterization of the patients with antibodies against nodal-paranodal junction proteins in chronic inflammatory demyelinating polyneuropathy

Abstract

Objective: Antibodies against nodal-paranodal junction proteins have been detected in some patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which is a crucial step to define the most effective treatment strategies. In this paper, we tested the positive rates of these antibodies in CIDP and characterized the clinical and electrophysiological features of the antibodies-positive patients.

Methods: We prospectively recruited 47 patients with CIDP. We detected IgG antibodies against human neurofascin-155 (NF155), neurofascin-186 (NF186), contactin-1 (CNTN1), contactin-2 (CNTN2) and contactin-associated protein-1 (Caspr1), and identified the IgG isotype with cell-based assay (CBA). We collected the demographic, clinical, laboratory, and electrophysiological information of the patients that were seropositive.

Results: Five patients (10.6 %) had IgG against NF155, 3 (6.4 %) against Caspr1, 2 (4.3 %) against NF186 and 1 (2.1 %) against CNTN1. All the 11 antibody-positive patients (8 males and 3 females) presented with typical clinical features. Five of them needed assistance in walking, 5 had cranial nerve impairments and 3 had autonomic disturbances. The age at onset of the patients that were anti-NF155-positive was younger (19.60 ± 9.02 years vs. 55.33 ± 11.93 years, P = 0.003) than those that were anti-Caspr1-positive. No significant difference in the functional status was observed between these two groups. The action potentials of 11/79 (13.9 %) motor nerves and 62/93 (66.7 %) sensory nerves exhibited no response. Moreover, 16/68 (23.5 %) nerves presented conduction block and 13/68 (19.1 %) nerves presented temporal dispersion. Distal motor latency (DML) of ulnar nerve and tibial nerve tended to be longer (p = 0.008 and p = 0.006, respectively) in anti-NF155-positive patients than that in anti-Caspr1-positive patients. Of the 11 patients that were antibody-positive patients, corticosteroids were effective in 3/7 (42.9 %), intravenous immunoglobins (IVIG) were effective in 1/7 (14.3 %), and rituximab was effective in 6/8 (75.0 %).

Conclusions: Our findings validate the previous observation on the clinico-serological correlation between CIDP and antibodies against nodal-paranodal proteins. Of note, the damage on nerves is more severe in anti-NF155-positive patients than that in anti-Caspr1-positive patients during electrophysiological diagnosis.

Keywords: Antibodies; Chronic inflammatory demyelinating polyneuropathy; Contactin-associated protein-1; Neurofascin-155; Node of Ranvier.