Immunity,Bone Metabolism And Anti Inflammatory Therapy On Patients With Axial Spondyloarthritis

Part I: Analysis of peripheral blood lymphocyte subsets and cytokines in patients with axial spondylopathyObjective.Axial spondyloarthritis(Ax-Sp A),known as chronic inflammatory disease,predominantly affects the axial skeleton,such as the sacroiliac joint and spine.The main pathological changes were synovitis and attachment point inflammation.Immune activation leads to a destructive inflammatory response in the target tissue;Inhibition of autoinflammatory response can be effectively treated Sp A.Therefore,it is believed that the pathogenesis may be related to immunity.In this study,changes of peripheral blood lymphocyte subsets and cytokines in newly diagnosed Ax-Sp A patients with disease duration less than 4 years were observed to explore the relationship between inflammation and immunity.Methods.A single-center,cross-sectional clinical study was conducted.From July 2014 to June 2016 eligible patients initial diagnosis of Ax-Sp A patients who had a symptom duration of less than 4 years.Flow cytometry was used to detect peripheral blood lymphocyte subsets,cytokines and sacroiliac joint MRI.The BMO on the sacroiliac joint MRI was scored using the Canadian spinal arthritis research group SPARCC system.Results.The mean level of IL-2、IL-4、IL-6、IL-17 A andγ-interferon was higher than the reference value.It reflects that immune factors are involved in the development of Sp A.CD4+T was negatively correlated with SPARCC score,p = 0.04;so CD4+T is related to the active inflammation of Sp A.CD8+T cells,B cells,NK cells,IL-2,IL-4,IL-6,IL-6,IL-10,IL-17 a,IL-12,tumor necrosis factor,γ-interferon all had no correlation with the SPARCC score.Conclusion.Immune factors are involved in the development of Sp A.CD4+T is related to the active inflammation of SpA.Part II Change of bone density in axial spondyloarthropathyObjective.Osteoporosis is susceptible in patients of axial spondyloarthropathy.Low bone mineral density has been observed in early and developmental diseases.Systemic inflammation can increase bone resorption and reduce bone remodelling.Decreased mobility also is the mechanism of bone fragility.The spine is at increased risk of fractures.Fractures may cause severe neurological complications.But Ax-Sp A predominantly affects a young male population,doctors and patients often ignore bone mineral density.This study was to examine changes in bone mineral density(BMD)in patients with Ax-Sp A and compare with health control.In this study,the differences of bone density of femur neck and lumbar vertebrae in Ax-Sp A patients compared with the control group and the changes after treatment with NSAIDs were calculated.The purpose of this study was to investigate the effects of inflammation and anti-inflammatory therapy on bone mineral density in Ax-Sp A patients,so as to provide a basis for early detection of bone damage,guiding drug use and clinical therapeutic effect evaluation.Methods.A single-center,cross section study was conducted.25 Ax-Sp A patients were selected from September 2018 to January 2019,excluding postmenopausal women,elderly men and patients with bone metabolic diseases.The levels of erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP)were collected,the levels of serum N-terminal propeptide of type I procollagen(PINP)and beta C-terminal cross-linked(β-CTX)were tested,BMD at the hip and lumbar spine were assessed using dual energy x-ray absorptiometry.Bone marrow oedema(BMO)of the sacroiliac joint on MRI was quantified by applying the Spondyloarthritis Research Consortium of Canada(SPARCC)system.Normal control was healthy volunteers in the same hospital.BMD at the hip and lumbar spine were also assessed using same dual energy x-ray absorptiometry by same technician.SPSS version 17.0 was used for all statistical analyses.Student’s paired t-test was used.p<0.05 was considered as statistically significant.The associations between the BMD and ESR、CRP、SPARCC score were evaluated using pearson correlation(normal distribution)or spearman rank correlation(non-normal distribution).Results 25 patients with Ax-Sp A were recruited.In 5(20%)cases,6 sites(1 lumbar spine,5 femoral neck)met the bone mass reduction criteria,accounting for 12% of the total detection sites..The 5 patients included 3 males and 2 females,with an average age of 26.7 years for males and 43.5 years for females.All 5 patients patients had active sacroiliac joint inflammation..The difference of BMD of femoral neck was significant between Ax-Sp A patients and control group,but there was no significant difference of BMD of lumbar spine.No association was found between the BMD and ESR、CRP、SPARCC score,but the level of serum PINP was correlated with BMD of femoral neck.The changes of bone metabolism markers PINP and β-CTX before and after treatment were not statistically significant.Conclusion Bone metabolism of patients with Ax-Sp A is obviously abnormal.They have a higher incidence of OP than normal people.Patients with active inflammation of sacroiliac joint are more likely to develop OP.OP predominates in femoral neck.OP is characterized by high conversion type.The changes of bone metabolic markers in Sp A patients were not significantly affected by NSAIDs therapy for 3 months.Part Ⅲ Effect analysis of anti-inflammatory treatment for active axial spondyloarthritisObjective.Compared with pelvic radiograph,magnetic resonance imaging(MRI)of the sacroiliac joint contributes to a better understanding of the course of the disease and to an earlier diagnosis,so MRI have been extensively used to detecte inflammation of the sacroiliac joint.The most important active inflammatory lesions of the sacroiliac joint on MRI are bone marrow oedema(BMO).Nonsteroidal antiinflammatory drugs(NSAIDs)are recommended first-line therapy for all patients with Sp A.Until now,limited data show effect of long-term treatment with NSAIDs on active sacroliitis,so the main aim of this study was to assess the efficacy of long-term NSAIDs treatment on MRI BMO of the sacroiliac joint in newly diagnosed axial Sp A with a symptom duration of less than 4 years.The results were compared with TNF-α antagonist and control group.Methods.This study is a double-arm single center clinical study.From July 2014 to June 2016 eligible patients who had MRI-determined BMO of the sacroiliac joint at baseline,had a symptom duration of less than 4 years.After the baseline MRI,an optimal dose of NSAID was administered for 24 weeks or 48 weeks.Sacroiliac joint MRI was performed again at the end of the study.BMO of the sacroiliac joint was quantified by applying the Spondyloarthritis Research Consortium of Canada(SPARCC)system.The levels of erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP)were determined at each visit.Disease activity was expressed using the ASDAS.ASDAS clinically important improvement(ASDAS CII,decrease from baseline ≥1.1),ASDAS major improvement(ASDAS MI,decrease from baseline ≥2.0),ASDAS inactive disease(ASDAS ID,score <1.3),ASAS-20 response,ASAS-40 response and ASAS partial remission were calculated at week 24 or week 48.Primary end point were improvement in BMO of the sacroiliac joint at week 24 or week 48.ESR,CRP,sacroiliac joint MRI and SPARCC scores were measured 48 weeks later in the TNF-α antagonist group and the control group.SPSS version 17.0 was used for all statistical analyses.p<0.05 was considered as statistically significant.To analyze the change in SPARCC score and ASDAS-CRP from baseline to follow-up,Student’s paired t-test was used,since SPARCC score and ASDAS-CRP were distributed normally.Due to the skewed distribution,the nonparametric Wilcoxon signed rank test was used to analyze the change in ESR and CRP from baseline to follow-up.The associations between the changes in SPARCC score and the changes in clinical variables were evaluated using pearson correlation or spearman rank correlation.Results.43 patients were recruited at baseline,and 33 patients eventually completed the study,including 10 patients having follow-up MRI at week 24 and 23 patients having follow-up MRI at week 48.There is no crossover between the two subgroups.The median NSAID index was 89.5(rang 83.3-96.7)in all 33 patients.Overall,the mean of SPARCC score decreased from 21.8 ± 16.1 at baseline to 10.2 ± 12.8 at follow-up(p<0.001).75.8% of the patients displayed a minimally important change and 30.3% became free of BMO.The mean of ASDAS-CRP decreased from 3.1 ± 1.0 at baseline to 2.1 ± 1.0 at follow-up(p<0.001).48.5% of the patients acquired a ASDAS CII,including 21.2% gaining a ASDAS MI,and 15.2% became ASDAS ID.There were 66.7% of the patients meeting ASAS-20 response criteria,45.5% meeting ASAS-40 response criteria,and 24.2% meeting ASAS partial remission criteria.Although there was a trend toward a slightly better response on MRI and clinical assessments at week 48 compared to week 24,the difference was not statistically significant.No serious adverse events related to NSAIDs were reported during the study period.The SPARCC score decreased significantly after TNF-α antagonist treatment.The SPARCC score was significantly higher in the control group.The difference between the three groups was statistically significant.Conclusion.Long-term oral NSAIDs drugs can significantly reduce the sacroiliac joint BMO and clinical disease activity of Ax-Sp A patients.The curative effect was better than the control group and worse than the TNF-antagonist.However,NSAIDs is suitable for long-term use,effective,safe and economical,in line with China’s national conditions.