A Research Related To The Effects Of Tumor Necrosis Factor Alpha On The Treatment Of Adalimumab And Regulatory T Cells In Active Ankylosing Spondylitis

Objective:1.According to the baseline of TNF alpha,to observe the response and changes of Treg cells in patients of active ankylosing spondylitis after been treated with Adalimumab.2.To discuss the effect and possible mechanism of the Treg cells before and after treatment of adalimumab in patients with moderate and severe ankylosing spondylitisMethods:1.This study is based on a randomized,double-blind,phase III clinical trials of adalimumab parallel comparison,according to the inclusion and exclusion criteria,Twenty-four patients were successfully enrolled.They came from outpatients the Second Hospital of Shanxi Medical University from January 2017 to December 2017.They all signed informed consent.They were treated with adalimumab every other week regular,40mg every time.Finally,Twenty-four patients were treated for 12 weeks and Twenty-three were treated for 24 weeks.2.We collected clinical data before the first administration of the drug,as well as the2^th,4 ^th,8 ^th,12 ^th,18 ^th,24 ^th week.Including patient general condition ratings,spinal pain score,BASDAI,BASFI,BASMI,ASDAS-CRP,SF-36scale,EQ-5D evaluation,MASES,thoracic mobility,swelling joint number?44 joints?and tenderness joints?46joints?.At the same time,we also examined blood routine,urine routine,liver and kidney function,c-reactive protein and erythrocyte sedimentation rate.3.The 0 ^th,4 ^th,12 ^th and 24 ^thh week after the administration of the drug,4ml of the elbow venous blood was taken in the morning when patients were on an empty stomach.After the static and centrifugation,it was stored in the-80 refrigerator to store.TNF-alpha was detected by enzyme-linked immunosorbent assay?ELISA?.According to literature,previous research results and the baseline of TNF alpha,the 24 patients were divided into three groups:low TNF alpha group,middle TNF alpha group,and high TNF alpha group.4.Curative effect index1).Main curative effect indexAfter 4 weeks and 12 weeks of treatment,the proportion reached the standard of ASAS20 in the three groups.2).Secondary curative effect indexAfter 24 weeks of treatment,the proportion reached the standard of ASAS20 in the three groups.After 4week,12week and 24 weeks of treatment,the proportion reached the standard of ASAS40,ASAS5/6 and BASDAI50 in the three groupsAfter 4weeks,12weeks and 24weeks of treatment,changes of BASFI,BASMI,ASDAS-CRP,c-reactive protein and erythrocyte sedimentation rate in three groups.5.We selected 27 volunteers as healthy control group in our hospital physical examination center.Peripheral blood was collected after the first and 24^th week of administration.The absolute number of total CD4+T cells,CD8+T cells,B and NK cells in peripheral blood was determined by using a BD TrucountTM tube with a certain number of magnetic beads,and then the absolute number of CD4+Treg cells was calculated.Comparing the level of Treg cells in AS patients and the healthy control group.Observe the changes of Treg cells after been treated with adalimumab in patients with AS.Results:1.Change of main curative effect indexAfter 4 weeks of treatment,the proportion of ASAS20 in the lower,middle and high groups was 85%,70%,0,and the total proportion was 54%.After 12 weeks,the proportion of ASAS20 in low,middle and high groups was 100%,80%,42%and 75%respectively.The ratio of ASAS20 of the three groups was statistically significant after 4 weeks and 12 weeks of treatment?P<0.05?.The difference between low TNF group and high TNF group was statistically significant after 4 weeks?P<0.017?.The difference between middle TNF group and high TNF group was statistically significant after 4 weeks?P<0.017?.2.Secondary curative effect index changesAfter 4 weeks and 12 weeks of treatment,the ratio of ASAS40 and ASAS5/6 was statistically significant of the three groups?P<0.05?.There was no significant difference in the proportion of BSDAI50 of the three groups?P>0.05?.After 24 weeks of medication,there was no significant difference in the proportion of ASAS20,ASAS40,ASAS5/6 and BSDAI50 among the three groups?P>0.05?.With the prolongation of treatment time,the index of BASFI,BASMI,ASDAS-CRP,CRP and ESR were all decreased.3.Comparing the level of TNF alpha in the three groups after 4,12,and 24 weeks of treatmentCompared with the baseline level,the level of TNF alpha in the three groups decreased firstly,slightly increased and then decreased after 4 weeks,12 weeks and 24weeks of treatment.After 12 weeks and 24 weeks of medication,the change rate of TNF alpha in the middle and the high TNF alpha group was higher than that the low TNF alpha group.The difference was statistically significant?P<0.01?.4.Comparison of absolute count of Treg cells between AS patients and healthy controlsAt baseline,the absolute count of Treg cells in AS group was lower than healthy controls,and the difference between the two groups was significant?P<0.05?.The difference between low TNF alpha group and high TNF group was statistically significant?P<0.05?.5.Comparison of absolute count of Treg cells before and after received adalimumab treatment?0 weeks,24 weeks?in three groupsAfter 24 weeks of medication,the absolute count of Treg cells in the lower,middle and high groups showed an increasing trend,and the difference between the groups before and after treatment was significant?P<0.05?.Conclusion1.The effect of adalimumab in the treatment of moderate and severe ankylosing spondylitis is significant.2.At the same dose,AS patients with low TNF alpha level at baseline were easy to get ASAS20 relief in a short time.On the contrary,the higher the TNF alpha level was,the longer the administration time needed.3.The decrease of the absolute count of Treg cells plays a role in the pathogenesis of AS.4.Adalimumab may promote the growth of Treg cells.