lactoferrin and Guillain-Barre-Syndrome

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.

Topics: Adult; Aged; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Autoantibodies; Child; Cranial Nerves; Enzyme-Linked Immunosorbent Assay; Female; Gangliosidosis, GM1; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Lactoferrin; Leukocytes; Male; Microscopy, Confocal; Middle Aged; Phagocytosis; Receptors, IgG; Severity of Illness Index

Free radicals are molecules that contain at least one unpaired electron and by nature are highly reactive and potentially destructive. Free radical damage can play an important role of demyelination. Glutathione peroxidase, which plays a role in free radical defenses, and myeloperoxidase and lactoferrin, which are considered to reflect the strength of oxidative stress, were examined by monoclonal antibody-based enzyme immunoassay on serum samples taken from patients with neuroimmunological disorders, namely, 35 multiple sclerosis(MS), and 2 Baló disease, 10 Guillain-Barré syndrome(GBS), and 25 human T-lymphotropic virus type-1 associated myelopathy (HAM). The levels of glutathione peroxidase in active phase of MS (8.37 +/- 5.59 micrograms/ml: p < 0.05) were increased rather than in inactive phase (5.05 +/- 2.44 micrograms/ml) and control (5.41 +/- 1.40 micrograms/ml), the levels of myeloperoxidase in HAM (95.5 +/- 89.1 ng/ml: p < 0.05) were increased rather than in controls (21.5 +/- 4.1 ng/ml), and the levels of lactoferrin were not significantly increased than in other disease and control. Moreover the levels of myeloperoxidase and lactoferrin are increased in Baló disease (myeloperoxidase 487, 762 ng/ml; not significant, lactoferrin 2.58, 2.77 ng/ml; not significant) than in control (myeloperoxidase 21.5 +/- 4.1 ng/ml, lactoferrin 0.69 +/- 0.32 ng/ml). In conclusion, we have here first demonstrated that the levels of these enzyme were not paralleled in MS and Baló diseases. In GBS the levels of all these enzyme were not increased. Thus, these findings suggest that these enzyme may play an important role of the disease activity of Baló, and may reflect the activity of the defense of MS.

Topics: Adult; Diffuse Cerebral Sclerosis of Schilder; Free Radicals; Glutathione Peroxidase; Guillain-Barre Syndrome; Humans; Lactoferrin; Middle Aged; Multiple Sclerosis; Oxidative Stress; Paraparesis, Tropical Spastic; Peroxidase