Intrathecal anti-alphaB-crystallin IgG antibody responses: potential inflammatory markers in Guillain-Barré syndrome.
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.
Wanschitz
Julia
J
Clinical Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Ehling
Rainer
R
Löscher
Wolfgang N
WN
Künz
Betinna
B
Deisenhammer
Florian
F
Kuhle
Jens
J
Budka
Herbert
H
Reindl
Markus
M
Berger
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation / Q000276:immunology; D000941:Antigens / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D005727:Ganglia, Spinal / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000134:cerebrospinal fluid* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid*; D007150:Immunohistochemistry; D007249:Inflammation / Q000097:blood / Q000134:cerebrospinal fluid* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009475:Neurons, Afferent / Q000276:immunology / Q000473:pathology; D010525:Peripheral Nerves / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D011237:Predictive Value of Tests; D013346:Subarachnoid Space / Q000276:immunology; D038203:alpha-Crystallin B Chain / Q000097:blood / Q000276:immunology*
D000941:Antigens; D015415:Biomarkers; D007074:Immunoglobulin G; D038203:alpha-Crystallin B Chain