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The Expression Of FcγRⅡB In Myasthenia Gravis And Its Correlation With Anti-AChR-Ab

Posted on:2010-11-16Degree:MasterType:Thesis
Country:ChinaCandidate:A JianFull Text:PDF
GTID:2144360278469124Subject:Department of Neurology
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Background:Myasthenia gravis is a T-cell dependent;anti-AChR antibody mediated autoimmune disease that affects the neuromuscular junction.The fundamental pathological mechanism of MG is thought to be the loss of AChR located at the neuromuscular junction endplate postsynaptic membrane.AChR-Ab which produced solely by activated B lymphocytes is the main autoantibody of MG and the direct cause which leads to morbid muscle weakness.FcγRⅡB,an inhibitory receptor which is able to bind to the Fc fragment of IgG with low affinity,is one member of the IgG Fc fragment receptor family that located on the surface of all kinds of cells and the only one Fc receptor that expresses on the surface of B lymphocyte.FcγRⅡB is crucial in the modulation and maintenance of immune balance.This study is aimed to explore the effect of FcγRⅡB in the pathogenesis of MG by observing the expression of FcγRⅡB on both transcription and protein levels in peripheral B lymphocytes, detecting the serum level of anti AChR-IgG and then analyze the correlation between them,so as to determine the role of FcγRⅡB in the immune etiology of myasthenia gravis.Objective:to explore the role of FcγRⅡB in the pathogenesis of MG by testing the expression of FcγRⅡB mRNA and FcγRⅡB protein in peripheral B lymphocytes of both MG patients and healthy controls, comparing the differences of the expression level of the two items between MG patients and normal controls;detecting the corresponding serum level of IgG type anti-AChR antibody in MG patients,analyzing the correlation between the expression level of FcγRⅡB,FcγRⅡB mRNA and AChR-Ab.Methods:The expression level of FcγRⅡB mRNA in peripheral B lymphocytes extracted from myasthenia gravis patients and normal controls was tested by semi-quantitative RT-PCR;the expression level of FcγRⅡB on the surface of peripheral B lymphocytes of both MG patients and normal controls was tested by flow cytometry;the serum level of IgG type AChR-Ab was detected by indirect ELISA,then analyze the correlation between them.Results:1.The definite relative OD value of FcγRⅡB1mRNA and FcγRⅡB2mRNA in B cells of the 18 AChR-Ab positive MG patients is 0.59±0.12 and 0.38±0.17 respectively while in the 18 normal controls the value is 1.09±0.19 and 0.68±0.17 separately.The expression level of both FcγRⅡB1mRNA and FcγRⅡB2mRNA decreased obviously in MG patients compared with normal control group,the statistical difference of which is significant(P<0.01).2.The relative OD value of FcγRⅡB lmRNA and FcγRⅡB2mRNA in the 11 ocular MG patients is 0.58±0.14 and 0.36±0.16 respectively while in the 7 generalized MG patients the numerical value is 0.61±0.08 and 0.41±0.18 separately.The expression level of the two items presents no significant difference between the two subgroups(P>0.05).3.The expression rate(%) of FcγRⅡB on the surface of peripheral B cells in MG group and normal control group is 5.99±0.68 and 10.67±1.39 respectively.The expression level of FcγRⅡB on the surface of B lymphocytes in MG group is lower than normal control group.The statistical difference is significant(P<0.05).4) The OD value of serum anti-AChR IgG in PCR group is 0.42±0.08 while in flow cytometry group the value is 0.35±0.07.Anti AChR-IgG level presents an obvious negative correlation with the expression level of both FcγRⅡB1mRNA and FcγRⅡB2mRNA,the correlation coefficient is -0.757 and -0.794 respectively(P<0.01).Anti AChR-IgG level shows a negative correlation with the expression rate of FcγRⅡB as well and the correlation coefficient is -0.767(P<0.05).Conclusion:Lower expression of FcγRⅡB may lead to reduced negative regulation of the activation of B lymphocytes,resulting in the hyper activation of B cells and massive production of auto antibody such as anti-AChR that causes MG.This may be an important step in the pathogenesis of MG.
Keywords/Search Tags:FcγRⅡB, myasthenia gravis, B lymphocytes, anti-AChR-Ab
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