RESUMO
The pathogenesis of Guillain-Barré Syndrome (GBS) is not entirely understood, but includes infection-induced aberrant immune responses. Genetic polymorphisms in Fc gamma receptor genes (FCGR) have been associated with GBS. We assessed whether polymorphisms rs1801274 in FCGR2A and rs396991 in FCGR3A were associated with GBS in a Brazilian population. We genotyped 141 GBS cases and 364 healthy controls from Brazil for both polymorphisms. The FCGR genotypes and alleles frequencies did not differ significantly between GBS and controls. In addition, there was no genetic association with either severity or clinical outcomes. We conclude that these FCGR polymorphisms are not associated with susceptibility to Guillain-Barré Syndrome in this Brazilian population.
Assuntos
Síndrome de Guillain-Barré/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de IgG/genética , Adulto , Anticorpos/sangue , Brasil , Feminino , Gangliosídeos/imunologia , Estudos de Associação Genética , Genótipo , Síndrome de Guillain-Barré/sangue , Síndrome de Guillain-Barré/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) are pleiotropic molecules with widespread action in autoimmune diseases. OBJECTIVE: This study characterizes the distribution of iNOS and TNF-alpha in the spinal nerve roots, dorsal root ganglia and sciatic nerve of Lewis rats during experimental autoimmune neuritis (EAN). METHODS: Macrophages and neutrophils were identified by immunofluorescence as cellular sources of iNOS and TNF-alpha at various stages of EAN induced by synthetic peptide 26. RESULTS: As the disease progressed, iNOS- and TNF-alpha-bearing cells gradually infiltrated the cauda equina, dorsal root ganglia, Th12-L3 spinal roots, and the sciatic nerve. A severer EAN profile developed when more iNOS- and TNF-alpha-bearing cells were present, and the recovery from EAN was related to the disappearance of these cells and the regeneration of nerve fibers. CONCLUSIONS: This is the first report to show iNOS- and TNF-alpha-immunoreactive cells in dorsal root ganglia during EAN, suggesting an underlying pathology for the neuropathic pain behavior in EAN. Our results suggest that the cells bearing iNOS and TNF-alpha in the different parts of the peripheral nervous system are involved in the development of the clinical signs observed at each stage of EAN.
Assuntos
Neurite Autoimune Experimental/imunologia , Neurite Autoimune Experimental/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Sistema Nervoso Periférico/imunologia , Sistema Nervoso Periférico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Modelos Animais de Doenças , Gânglios Espinais/imunologia , Gânglios Espinais/metabolismo , Gânglios Espinais/fisiopatologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/metabolismo , Síndrome de Guillain-Barré/fisiopatologia , Macrófagos/imunologia , Macrófagos/metabolismo , Neuralgia/imunologia , Neuralgia/metabolismo , Neuralgia/fisiopatologia , Neurite Autoimune Experimental/fisiopatologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Óxido Nítrico/metabolismo , Paresia/imunologia , Paresia/metabolismo , Paresia/fisiopatologia , Sistema Nervoso Periférico/fisiopatologia , Ratos , Ratos Endogâmicos Lew , Recuperação de Função Fisiológica/imunologia , Nervo Isquiático/imunologia , Nervo Isquiático/metabolismo , Nervo Isquiático/fisiopatologia , Raízes Nervosas Espinhais/imunologia , Raízes Nervosas Espinhais/metabolismo , Raízes Nervosas Espinhais/fisiopatologiaRESUMO
Gangliosides are glycolipids mainly present at the plasma membrane (PM). Antibodies to gangliosides have been associated with a wide range of neuropathy syndromes. Particularly, antibodies to GM1 ganglioside are present in patients with Guillain-Barré syndrome (GBS). We investigated the binding and intracellular fate of antibody to GM1 obtained from rabbits with experimental GBS in comparison with the transport of cholera toxin (CTx), which binds with high affinity to GM1. We demonstrated that antibody to GM1 is rapidly and specifically endocytosed in CHO-K1 cells. After internalization, the antibody transited sorting endosomes to accumulate at the recycling endosome. Endocytosed antibody to GM1 is recycled back to the PM and released into the culture medium. In CHO-K1 cells, antibody to GM1 colocalized with co-endocytosed CTx at early and recycling endosomes, but not in Golgi complex and endoplasmic reticulum, where CTx was also located. Antibody to GM1, in contraposition to CTx, showed a reduced internalization to recycling endosomes in COS-7 cells and neural cell lines SH-SY5Y and Neuro2A. Results from photobleaching studies revealed differences in the lateral mobility of antibody to GM1 in the PM of analyzed cell lines, suggesting a relationship between the efficiency of endocytosis and lateral mobility of GM1 at the PM. Taken together, results indicate that two different ligands of GM1 ganglioside (antibody and CTx) are differentially endocytosed and trafficked, providing the basis to gain further insight into the mechanisms that operate in the intracellular trafficking of glycosphingolipid-binding toxins and pathological effects of neuropathy-associated antibodies.