Intrathecal anti-alphaB-crystallin IgG antibody responses: potential inflammatory markers in Guillain-Barré syndrome

J Neurol. 2008 Jun;255(6):917-24. doi: 10.1007/s00415-008-0815-9. Epub 2008 Jul 11.

Abstract

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

Methods: Anti-alphaBC-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 alphaBC. Expression of alphaBC was immunohistochemically analyzed in postmortem peripheral nerve tissue of GBS and controls without neuropathy.

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

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibody Formation / immunology
  • Antigens / blood
  • Antigens / cerebrospinal fluid
  • Antigens / immunology
  • Biomarkers / analysis
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Female
  • Ganglia, Spinal / immunology
  • Ganglia, Spinal / pathology
  • Ganglia, Spinal / physiopathology
  • Guillain-Barre Syndrome / blood
  • Guillain-Barre Syndrome / cerebrospinal fluid*
  • Guillain-Barre Syndrome / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid*
  • Immunohistochemistry
  • Inflammation / blood
  • Inflammation / cerebrospinal fluid*
  • Inflammation / immunology*
  • Male
  • Middle Aged
  • Neurons, Afferent / immunology
  • Neurons, Afferent / pathology
  • Peripheral Nerves / immunology
  • Peripheral Nerves / pathology
  • Peripheral Nerves / physiopathology
  • Predictive Value of Tests
  • Subarachnoid Space / immunology
  • alpha-Crystallin B Chain / blood
  • alpha-Crystallin B Chain / immunology*

Substances

  • Antigens
  • Biomarkers
  • Immunoglobulin G
  • alpha-Crystallin B Chain