Estudi fisiopatològic de l'acció d'anticossos IgM anti-GM2 d'un pacient sobre la unió neuromuscular.

Identificador:  TDX:631

Handle: https://hdl.handle.net/20.500.11797/TDX631

Autors:  Sabaté Martínez, Maria del Mar

Resum:
Objective:<br/><br/>To determine the action of anti-gangliosides antibodies of a patient with a chronic motor demyelinating polyneuropathy associated with a IgM monoclonal component on the nerve conduction and on the neurotransmission of a adult mammalian both in a acute and chronic study and, to investigate that the gangliosides are involved in the entry of calcium in the nerve. <br/><br/>Methods:<br/><br/>Determination the serum specificity of the patient with ELISA and immuneHPTLC techniques using commercial and purified gangliosides of bovine brain, human brain and YAC-1 cells. <br/>IgM antibodies purifying with affinity chromatography with goat antibodies against human IgM.<br/>Immunehistochemistry techniques to search the antibody fixation at the presynapticc region of the neuromuscular junction. <br/>Passive transfer of anti-gangliosides antibodies into the LAL muscle of mice, every 24 h during 15 days. Utilization of prendisolone to reduce the inflammatory response. The controls followed the same protocol but the injection contain desnaturalized IgM (90 ºC, 20 min) and other physiological solution on the muscle. <br/>Conventional electrophysiological studies of motor to determinate compost motors action potentials.<br/>Intracellular electrophysiological studies to investigate the serum of patient effect (and the this monoclonal component) both in acutes incubations and in the muscles chronically treated with the anti-gangliosides IgM.<br/><br/>Results and conclusions:<br/><br/>We are made a study about the paper of the serum of a patient with a chronic motor desmielinating polineuropathy associated and an IgM monoclonal component that showed affinity for the GM2 on the neuromuscular junction. The electrophysiological acute studies in vitro have showed that that IgM induced a neuromuscular transmission reduction by the block of calcium entry through the calcium channels dependent voltage P/Q types, probably by the alteration of a regulatory mechanism controlled for gangliosides. In this study we also have found that the gangliosides against the antibodies of patient are normally localized in the region of the neuromuscular synapses (both in the axon and the Schwann cell) and in the intramuscular nerve (both in the myelin and the motor axon). The chronic passive transfer of antibodies anti-gangliosides on the adult mammalian muscle induced morphological alterations, (synapses with sprouts and/or axonal retractions) and functional alterations (neurotransmission block and a new calcium channel were found) on the neuromuscular junctions. In that muscles, the motor neurographies showed axonal conduction block.