Expression Of Tfh Cells And Molecules In Peripheral Blood From OMG And GMG Patients

Myasthenia gravis (MG) is an acquired autoimmune disease. Pathological changesoccur in the neuromuscular junction and block the the function of AchR at post-synapticsites of neuromuscular junction. The specific antibodies combined with the acetylcholinereceptors(AchR) at the neuromuscular junction postsynaptic membrane, damage thestructure of postsynaptic membrane.This antibodies impair the signal transmission atneuromuscular junction.The pathological changes cause MG patients skeletal muscle easyto fatigue, the severity of the symptoms will aggravate after patients physicalactivities,and mitigate after application of cholinesterase inhibitors. MG has a typicalphenomenon,the skeletal muscle faintness mitigate in the morning but aggravate at night.The antigen-antibody reaction plays a key role in the pathogenesis of MG process. MG isthe autoimmune disease, which is caused by the humoral immune response.It is generallybelieved that the antibodies produced in vivo combine with the AchR at neuromuscularjunction,then complements would be activated and form the membrane attackcomplex(MAC).The MAC impair AchRs at neuromuscular junction and destroy thepostsynaptic membrane. Because the number of AchRs decrease and structure of AchRs is damaged, the capability of production of action potential(AP) decline. So the nervestimulation can not cause the skeletal muscle contraction.It is recognized that thymus is a key organ and abnormal immune response withinthymus is closely related to MG occurrence and development. The abnormal immuneresponse will also lead to antigen-specific antibody production. Normal thymus accountesfor the proportion of15-20%of MG patients,78-80%of MG patients haveabnormal-thymus with varying-degree malformatiom.thymus hyperplasia accountes for65-75%, thymoma accountes for10-15%. The thymus is the central space in T cellsdifferentiation and maturity. There are mainly two ways to eliminate abnormal T cellclones through T cell differentiation, maturation in thymus. The positive selection is onlyallowed T cell clones to survive, which is able to identify MHC molecules. The negativeselection eliminates two T clones, the one has a strong affinity with MHC molecules, theother has affinity with self-antigen as well as identification of MHC molecules. It can besaw that thymus plays an important role in the formation and maintenance of immunetolerance. the immune tolerance includes central tolerance and peripheral tolerance. If theimmune tolerance is impaired through some mechanisms, the specific autoimmune T cellswill be generated. The auto-T cells work directly, or produce a variety cytokine.Theautoimmune diseases will be induced.MG is the result of acetylcholine receptor-specific antibodies effection. Whileantibody production is a direct result of the differentiation of B cells into plasma cells, andthe antibody titer is closely related to number of plasma cells and its functional status. Inthe process of B cells differentiate into plasma cells, a new CD4+T cell subset isrecognized lately, this CD4+T cell subset plays a vital role in B-cell proliferation. thesecells migrate into the lymphoid follicles and help B cells differentiate and then produceantibodies. Due to the above reasons, this new CD4+T cell subset is so called follicularhelper T cells (Tfh cell). Tfh cells are different from the other T cell subsets, Tfh cellshave more powerful than other T cell subsets on helping B cell proliferation anddifferentiation.This cells have a great effect on transformation of antibody classes andpromote the plasma cells to secret antibodies.MG is a main result of the humoral immune mediated by Tfh cells and B cells, this two cells interaction may play an important role inMG pathogenesis. This experiment detected the molecular expression on Tfh cells inperipheral blood of patients with MG by flow cytometry method. the expression level ofCXCL13is detected in the serum at the same time. Through comparison with differentexpression of these molecules in peripheral blood,we can explain the effect of Tfh cells inthe pathogenesis of MG, as well as the relationship between QMG scores、absolute scoresand the CXCL13expression.MethodMG patients’ blood samples were taken for the study, treated from2011to2012, indepartment of neurology Tangdu Hospital, including OMG14patients, GMG22patients,11normal control11patients. Using FCM analyze different molecularexpression on Tfh cells between OMG and GMG patients in peripheral blood. This studyrepresents CD4+CXCR5+T cells as the Tfh cells, so the different molecules expressionof the Tfh cells can be observed between the different groups. At the same time, analysisof the different expression of CD4+Bcl-6+T cells, CD4+ICOS+T cells between theOMG and GMG group, as well as analysis of the different expression of CXCL13between different groups. So which kind of molecules associated with MG and thesymptoms severity would be cleared, These results can predict the progression of thedisease.Result:CXCR5expression in peripheral blood increased,CXCR5+CD4+T cells fromcontrol group, OMG and GMG goup，accounted for9.5±2.3%,12.0±1.8%,14.2±2.1%, respectively，the proportion of CD4+T cells. The lowest expression was incontrol group,and the highest expression was in GMG group, by analysis of variance,ithad a statistical difference among the three groups (p <0.05);2.ICOS expression inperipheral blood: ICOS+CD4+T cells accounted for0.09±0.02%,0.11±0.02%,0.14±0.05%, respectively, the proportion of CD4+T cells. the lowest was in the control group,the highest was in GMG group. While no statistically significant difference accouredamong the three groups (p>0.05);3.Bcl-6expression in peripheral blood increased. Bcl-6 +CD4+T cells accounted the proportion for CD4+T cells were2.41±0.35%,3.32±0.41%,3.98±0.36%, respectively. By analysis of variance, there was a statisticaldifference among the three groups (p <0.05);4CXCL13expression in peripheral bloodfrom OMG and GMG patients increased.The percentages were0.63±0.13%,1.01±0.42%,2.40±0.89%, respectively. It has a statistical difference among the three groups(p <0.05);5It had a certain relationship between the QMG scores、absolute scores andCXCL13expression.The coefficient of correlation were0.669and0.797, respectively.