Volume 223, December 2022, 107521AbstractObjective

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.

Introduction

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is classified into typical CIDP and CIDP variants, the latter of which include multifocal, focal, distal, motor, and sensory CIDP [1]. The hallmark of typical CIDP is chronically progressive or recurrent, symmetric weakness and sensory dysfunction of all extremities. The pathological manifestations of typical CIDP are demyelination mediated by macrophages [2]. The current available therapies for CIDP include corticosteroids treatment, plasma exchange and IVIG [3], [4], [5]. However, a subgroup of patients are refractory to IVIG. A previous study based on Spanish cohort suggested that antibodies against the node of Ranvier are biomarkers of the patients with CIDP who are resistant to IVIG [6]. Recently, antibodies against the node of Ranvier have been detected in some patients with CIDP [7], [8], [9]. Here, we aimed to assess the positive rates of the antibodies in patients with CIDP and characterize the clinical and electrophysiological features of the patients that were antibodies-positive. Considering the little information available about the associated features of antibodies against Caspr1, we described the clinical and electrophysiological features of three patients who were anti-Caspr1-positive and compared with those who were anti-NF155-positive.

Section snippetsPatients and data collection

We recruited patients with CIDP, who fulfilled the European Federation of Neurological Societies and Peripheral Nerve Society Diagnostic Criteria [10] diagnosed at Beijing Tiantan Hospital, Capital Medical University, between 2019 and 2020. All the participants were during progressive or relapsing stage of the disease. Patients with other chronic acquired demyelinating polyneuropathy, such as Polyneuropathy, Organomegaly, Endocrinopathy, M protein, Skin abnormality Syndrome, multifocal motor

Positive rates of antibodies

Five (10.6 %) serum samples were positive for NF155-IgG. Three (6.4 %) serum samples were positive for Caspr1-IgG. Two (4.3 %) serum samples were positive for NF186-IgG (one coexisting with low-titer NF155-IgG). One (2.1 %) serum sample was positive for CNTN1-IgG coexisting with low-titer NF186-IgG. The reactivity of one serum sample with anti-NF155 IgG4 is shown in Fig. 1. None of the serum samples was positive for CNTN2-IgG. All CSF samples from seropositive patients were IgG-positive

Conclusion

In the present study, we assessed the positive rates of antibodies against nodal-paranodal proteins in CIDP and analyzed the correlation between the antibodies and CIDP. We herein compared the clinical and electrophysiological features between 3 anti-Caspr1-positive patients and 5 anti-NF155-positive patients.

The reported positive rate of anti-NF155 IgG4 was 10.0 % (4/40, by CBA) in America [12], 3.8 % (2/53, by CBA) in Spain [6], and 18.0 % (9/50, by flow cytometry) in Japan [13]. In European

Funding support

None.

Ethical approval

This study was approved by the Ethics committee of Beijing tiantan hospital affiliated to capital medical university.

CRediT authorship contribution statement

Meng Dong: Data collection and analysis, writing the script. Zaiqiang Zhang: Concept and formulation. Hongfei Tai, Shuo Yang, Xiaozhen Gao, Hua Pan: contributed to the discussion, reviewed and edited the manuscript.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Declaration of competing interest

The authors report no declarations of interest.

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