| Objective:To clarify the role of Sema4A in the pathogenesis of SLE,the expression of soluble Sema4A in plasm and membrane-bound Sema4A on peripheral blood cells were detected,and the correlation between soluble or membrane-bound Sema4A and clinical and laboratorial data was analyzed.Furthermore,to evaluate the clinical diagnostic value of Sema4A in SLE,the ROC curve was performed.Methods:A total of 44 female SLE patients were included,while 38 female RA patients and 30 female healthy individuals were collected as controls.Sema4A-expressing cells in CD4+CD11c+myeloid dendritic cells(mDCs),T cells,B cell and neutrophil from SLE were analyzed by flow cytometry.A total of 30 female SLE patients were included,while 23 female RA patients and 23 female healthy individuals were collected as controls.The concentration of soluble Sema4A in plasma by ELISA.Clinical and laboratory data of SLE were collected,to examined the correlation between Sema4A and SLEDAI,dsDNA antibody,anti-Sm antibody,anticardiolipin antibody,serum creatinine,or urinary albumin level.The diagnostic value of membrane-bound Sema4A and soluble Sema4A in SLE was evaluated by ROC curve.Result:①The concentration of soluble Sema4A was significantly higher in SLE plasma(3.13±1.16)ng/ml than in RA plasma(1.41±0.71)ng/ml and in healthy individuals(1.92± 1.09)ng/ml(p<0.001).②The expression rate(%)of Sema4A on mDCs had significant difference between in SLE(83.63±14.65)and in RA(52.00±22.06)or in healthy individuals(61.13±18.18)(p<0·001).③The average expression(MFI)of Sema4A on neutrophils from SLE was significantly increased(554.97±114.48)compared with healthy individuals(478.32±100.04)(p<0.05),and was not significantly different from RA(531.38±85.79).The average expression of Sema4A on CD4+T cells from SLE(608.19±97..23)was significantly increased compared with RA(545.88±67.28)and healthy individuals(540.92±66.97)(p<0.05).④Increased level of soluble Sema4A in plasma was positively correlated with the concentration of dsDNA antibodies(p<0.0001,r=0.7422).The level of membrane-bound Sema4A was not related to dsDNA antibodies.But the expression rate(%)of Sema4A on mDCs from SLE patients with dsDNA antibody-positive(88.79±10.55)was higher than dsDNA antibody-negative patients(79.92±15.59)(p<0.05).⑤The concentration of soluble Sema4A in SLE patients was negatively correlative with the levels of C3 and with C4(p<0.01,r=-0.5827;p<0.05,r=-0.461 7).There was negative correlation between membrane-bound Sema4A on CD4+CD11c+mDCs and C4(p<0.05,r=-0.3232),whereas,no significant correlation with C3.⑥The concentration of soluble Sema4A in SLE patients with proteinuria(3.94±1.38)ng/ml was significantly higher than in normal group(2.84±0.96)ng/ml(p<0.05).The concentration of soluble Sema4A in SLE patients was negatively correlative with the level of Hb(p<0.001,r=-0.7342).⑦Membrane-bound Sema4A level on mDCs and CD4+T cell were found to positively correlated with SLEDAI(p<0.05,r=0.325;p<0.05,r=0.363).⑧The ROC curve was used to evaluate the diagnostic efficacy of soluble Sema4A in SLE,which the area under the curve(AUC)was 0.859,the cut-off value was 1.78 ng/ml when the optimal cut-off point was selected,the corresponding sensitivity was 0.933,the specificity was 0.694,and the Youden index was 0.629.Meanwhile,according to the ROC curve of membrane-bound Sema4A on mDCs,the AUC was calculated to be 0.860,the cut-off value was 71.50%,the corresponding sensitivity was 0.860,the specificity was 0.735,and the Youden index was 0.596.Conclusion:①Elevated soluble and membrane-bound Sema4A may contribute to the production of dsDNA antibodies in SLE,suggests that Sema4A involvein the development of SLE,and mDCs,helper T cells and neutrophils may participate in its pathological process.②Soluble Sema4A and membrane-bound Sema4A has a strong ability to recognize SLE and to assess disease activity.Furthermore,soluble Sema4A is associated with SLE patients with anemia,and soluble Sema4A may assess kidney damage in SLE.Therefore,Sema4A may become a new laboratory diagnostic marker. |
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