Intrathecal anti-αB-crystallin IgG antibody responses: Potential inflammatory markers in Guillain-Barré syndrome

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Abstract

Objective

αB-crystallin (αBC), a small stress protein with cytoprotective and anti-apoptotic functions, is a potent antigen in autoimmune demyelinating diseases. To address the role of αBC in Guillain-Barré syndrome (GBS) we analyzed humoral responses against αBC in relation to clinical, electrophysiological and CSF features in GBS.

Methods

Anti-αBC-IgG antibodies were measured in serum and cerebrospinal fluid (CSF) of patients with GBS (n = 41), infectious inflammatory neurological diseases (n = 21), multiple sclerosis (n = 42), and other, non-inflammatory neurological disorders (n = 40) by ELISA using human recombinant αBC. Expression of αBC was immunohistochemically analyzed in postmortem peripheral nerve tissue of GBS and controls without neuropathy.

Results

Serum αBC-IgG antibody levels did not differ between disease groups, whereas αBC-IgG antibodies in CSF were increased in GBS and infectious inflammatory neurological diseases. Calculation of an antigen specific αBC-IgG index (αBC-Ig-GCSF × total IgGCSF)/(αBC-IgGSerum × total IgGSerum) revealed significantly elevated values in patients with GBS compared to other disease groups (p < 0.001). αBC-IgG indices exceeding a cut off value > 0.8 had an 85 % specificity and a 76 % sensitivity for GBS. αBC was overexpressed in dorsal root ganglia and spinal roots of autopsy cases with GBS.

Conclusions

We demonstrate increased αBC-IgG indices in a high proportion of our GBS patients, which reflect enhanced antigen-specific intrathecal antibody responses against abnormally expressed αBC in inflamed peripheral nerve tissue. Elevated αBC-IgG indices might therefore serve as markers of PNS inflammation and supplement currently used laboratory tests in the diagnosis of GBS.

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