Anti-GM1 IgG antibodies induce leukocyte effector functions via Fcgamma receptors.
Guillain-Barré syndrome (GBS) is an immune-mediated neuropathy, in which leukocytes and humoral components of the immune system proposedly initiate localized inflammation. An important pathogenic role for anti-GM1 ganglioside antibodies has been suggested. Therefore, we evaluated anti-GM1 IgG antibody-induced leukocyte effector functions such as degranulation and phagocytosis using serum of 24 GBS patients. Serum without anti-GM1 antibodies of 9 GBS patients as well as pooled serum from healthy individuals served as controls. Ten out of 15 (67%) of anti-GM1 IgG positive sera were capable of inducing leukocyte degranulation, and 8 out of 15 (53%) of anti-GM1 IgG positive sera were capable of inducing phagocytosis of GM1-coated beads. In all of these sera anti-GM1 antibody titers were >or=1:800. No leukocyte degranulation or phagocytosis was observed in control sera. Leukocyte activation was completely abrogated in the presence of IgG receptor (FcgammaR) blocking antibodies, suggesting a crucial role for leukocyte FcgammaR in GBS pathogenesis. No correlation of antibody titers with the extent of leukocyte activation, or severity of disease was observed. These data document the capacity of anti-GM1 IgG antibodies to activate leukocyte inflammatory functions, and suggest an important role for anti-ganglioside IgG antibodies in the pathogenesis of GBS.
Department of Neurology and Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Nina M
NM
van Sorge
Leonard H
LH
van den Berg
Karin
K
Geleijns
Jos A
JA
van Strijp
Bart C
BC
Jacobs
Pieter A
PA
van Doorn
John H J
JH
Wokke
Jan G J
JG
van de Winkel
Jeanette H W
JH
Leusen
W-Ludo
WL
van der Pol
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D002648:Child; D003391:Cranial Nerves / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016537:Gangliosidosis, GM1 / Q000097:blood / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007781:Lactoferrin / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal / Q000295:instrumentation; D008875:Middle Aged; D010587:Phagocytosis / Q000276:immunology; D017452:Receptors, IgG / Q000097:blood / Q000276:immunology*; D012720:Severity of Illness Index
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D017452:Receptors, IgG; D007781:Lactoferrin