Autoantibodies Against Collapsin Response Mediator Proteins Associated With Encephalopathy/Myelopathy: A Single-Center Retrospective Study

Abstract

Background: Collapsin response mediator protein (CRMP) consists of five subtypes (CRMP1-5), which share high homology and are expressed in the nervous system. Anti-CRMP2 and anti-CRMP5 antibodies (Abs) have been reported in autoimmune encephalitis (AE). This study retrospectively evaluated the diagnostic value of CRMP auto-Abs in patients with suspected immune-mediated encephalopathy/myelopathy.

Methods: Patients with encephalopathy/myelopathy attributed to autoimmune or infectious causes, as well as those with encephalopathy of unclear etiology, were recruited from our department between January 2017 and November 2019. Clinical data, as well as serum and/or cerebrospinal fluid (CSF) samples, were collected. Measurement of Abs against CRMPs in patient samples was performed using a cell-based assay (CBA) with HEK293 cells expressing CRMP proteins and confirmed by a tissue-based assay (TBA) with mouse brain sections.

Results: A total of 400 patients and 77 healthy controls were recruited. The male-to-female ratio of the patients was 0.88, and the average age was 39.22 ± 16.59 years. CBA testing was performed with 200 paired CSF and serum samples, along with 99 CSF samples and 101 serum samples. Of the patients, 22 (5.5%) presented with anti-CRMPs Abs. Anti-CRMP1 was the most commonly detected Ab (17/22, 77.3%), either alone or in combination with CRMP2 and CRMP3. Titers of anti-CRMPs Abs ranged from 1: 3.2 to 1:10 in CSF samples and 1:32 to 1:320 in serum samples. Patients with anti-CRMPs Abs experienced more headaches and had higher levels of chloride in CSF compared to those without anti-CRMPs Abs. Fourteen of the 22 patients with anti-CRMPs Abs were diagnosed with encephalitis, exhibiting a higher frequency of fever and headache, CSF pleocytosis, and more frequent treatment with immunotherapy, steroids, antibiotics, and antiviral therapy compared to non-inflammatory encephalopathy patients.

Conclusion: Anti-CRMPs Abs may indicate immune-mediated neuronal damage in encephalopathy, including encephalitis, and may serve as potential biomarkers for neuronal injury.

Keywords: Collapsin response mediator proteins; autoantibodies; biomarker; encephalitis; encephalopathy.