GalNAc-GD1a in human peripheral nerve: target sites of anti-ganglioside antibody.
BACKGROUND
The authors previously reported that immunoglobulin G (IgG) antibody to the ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a) is associated with the pure motor variant of Guillain-Barré syndrome (GBS). Elucidation of the localization of GalNAc-GD1a in human peripheral nerve tissue may lead to understanding of the pathogenetic role of anti-GalNAc-GD1a antibody in GBS.


METHODS
IgG anti-GalNAc-GD1a-monospecific antibody was purified from anti-GalNAc-GD1a antibody-positive rabbit sera through an affinity column. Anti-neurofilament-200 monoclonal and anti-HNK-1 monoclonal antibodies were used as the markers for axon and myelin. Immunohistochemical study using double fluorescence labeling technique was conducted in human ventral roots (VR), dorsal roots (DR), intramuscular nerves, and sural nerves. Human teased ventral fibers also were studied.


RESULTS
Anti-GalNAc-GD1a antibody immunostained an inner part of compact myelin and additionally a periaxonal-axolemma-related portion in the VR, small-diameter DR fibers, and IM nerves. In sural nerves, small fibers were selectively stained. In VR, the staining was localized in the paranodal region.


CONCLUSIONS
Anti-GalNAc-GD1a antibodies in patients' sera may bind to those regions in the VR and IM nerves where GalNAc-GD1a is localized, and may function in the pathogenesis of pure motor type GBS. Further investigation is needed to explain the discrepancy between the immunolocalization of GalNAc-GD1a in sensory nerves and the absence of sensory disturbance in patients with GBS with IgG anti-GalNAc-GD1a antibodies.
Kaida
K
K
Third Department of Internal Medicine, National Defense Medical College, Saitama-ken, Japan.
Kusunoki
S
S
Kamakura
K
K
Motoyoshi
K
K
Kanazawa
I
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000032:analysis / Q000276:immunology*; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology; D000939:Epitopes / Q000032:analysis / Q000276:immunology*; D005260:Female; D005732:Gangliosides / Q000032:analysis / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000276:immunology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000294:innervation; D009412:Nerve Fibers / Q000737:chemistry / Q000276:immunology; D010525:Peripheral Nerves / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits; D013126:Spinal Nerve Roots / Q000737:chemistry / Q000276:immunology; D013497:Sural Nerve / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D005732:Gangliosides; D007074:Immunoglobulin G; C055253:IV(4)-galactosyl-N-acetylganglioside GD1a