Clinical And Animal Model Research On Axial Spondyloarthritis

Part ? The multidisciplinary clinic improves diagnostic delay for patients with axial spondyloarthritisObjective: The aims of the study are to assess the diagnostic delay of axial spondyloarthritis(Sp A)and the potential benefit of a new multidisciplinary approach in Chinese patients.Methods: A retrospective study was performed among 208 axial Sp A patients according to ASAS classification criteria.Diagnostic delay was defined as time interval between onset of the disease-related symptoms and time of diagnosis;and physician-related diagnostic delay was defined as the time interval between the initial visit to a physician and time of diagnosis.Risk factors for diagnostic delay were evaluated.A multidisciplinary clinic was subsequently established and newly diagnosed axial Sp A patients were prospectively enrolled(n=49)in parallel with counterparts(n=31)newly diagnosed in a conventional rheumatology clinic in a different campus.Results: In the retrospective study,the median diagnostic delay and physician-related diagnostic delay of axial Sp A was 25.5 months and 10 months,respectively.Physician-related diagnostic delay >3 months was associated with more active disease(BASDAI)and more functional impairment(BASMI)even after adjusting for TNFi exposure.The risks for physician-related diagnostic delay include first visit to a non-rheumatologist,most frequently an orthopedist,and low education level(?9 years)of the patients.Following introduction of a multidisciplinary approach,at a joint clinic attended by a rheumatologist,orthopedist and nurse specialist working as a team,the median physician-related diagnostic delay was reduced to 1 month and this was significantly shorter than 9 months at the comparator conventional clinic(p<0.05).Conclusion: The multidisciplinary approach is a promising approach to solve physician-related diagnostic delay which is related to more active disease and worse functional impairment among patients with axial Sp A.Part ? Expression and relevance of CCN1 in peripheral blood from patients with axial spondyloarthritisObjective: To investigate CCN1 expression in peripheral blood from patients with axial spondyloarthritis and the relationship between the expression of CCN1 and the levels of ESR,CRP,BASDAI,BASFI and BASMI.Methods: A total of 60 patients with axial spondyloarthritis were enrolled in this study from January 2015 to December 2015.108 healthy people were included in the control group.The expression of CCN1 in peripheral blood was detected by ELISA.The correlation between ESR,CRP,BASDAI,BASFI,BASMI and CCN1 was analysed.The patients with axial Sp A were divided into two groups according to the median number of CCN1 to compare the CRP,BASDAI,BASFI,BASMI levels.O ne group was CCN1?119 ng / L group and the other group was CCN1> 119pg/ml group.Results: The level of CCN1 in healthy people was 45.49(25.13,59.16)pg/ml(mean 49.24 ± 31.33),while CCN1 in patients with axial spondyloarthritis was almost three times higher than that in healthy controls(119.7(92.3,148.5)pg/ml,mean 125.2 ± 44.42pg/ml).There was a statistically significant difference between the two groups(p<0.001).There was no significant correlation between CCN1 level and ESR,CRP,BASDAI and BASFI.No significant differences in ESR,CRP,BASDAI,BASFI and BASMI were found between CCN1?119 pg/ml group and CCN1>119pg/ml group.Conclusion: The level of CCN1 in peripheral blood from patients with axial spondyloarthritis is significantly higher than that in healthy control group,but the relationship between CCN1 and inflammation index,disease activity and function impairment is still to be further studied.Part ? A mouse model of spondyloarthritis and analysis of CCN1 expressionObjective: Axial spondyloarthritis is a chronic progressive inflammatory disease,which makes a tremendous difference in the quality of life.Its etiology and pathogenesis has not yet fully elucidated.In this part,we tried to set up a mouse model of spondyloarthritis,and analyzed the clinical phenotype,radiographic and pathological features similarity to human spondyloarthritis.We hope it can contribute to further research on the etiology and pathogenesis of spondyloarthritis.Methods: Proteoglycan from bovine nasal septum was used for subcutaneous immunisation of 14–16 week old female BALB/c mice.The first and third antigen injection(100ug proteoglycan protein)was given in complete Freund's adjuvant,and the same doses of antigen were injected as second boost in incomplete Freund's adjuvant.Results: PG immunised BALB/c mice began to develop peripheral arthritis in 7th week after the first antigen injection.The initial manifestation was the swelling of the peripheral joints.The peripheral arthritis score reached the peak at 12 th week since the first immunisation,with the inflammation and spur formation of the ankle and knee joint.We found infiltration of inflammation cells in intervertebral discs of the lumbar vertebrae and the caudal vertebrae.C hondrocyte proliferation can be see in the meniscus of knee and lumbar intervertebral discs.Besides,the expression of CCN1 can be detected in the caudal vertebrae and knee joint.At the 18 th week after the first immunisation,not only the caudal vertebrae and the lumbar vertebrae,but also the thoracic vertebrae and the cervical vertebrae had damaged intervertebral discs.Abundant chondrocyte cel s gathered in the intervertebral discs.Conclusion: The mouse model of spondyloarthritis established in this study can simulate the clinical phenotype of human spondyloarthritis,including inflammation and new bone formation in peripheral and axial joints.The local expression of CCN1 was also found in the mouse model.Part ? The therapeutic potential of CCN1 monoclonal antibody in spondyloarthritis mouse modelObjective: To investigate the therapeutic effect of CCN1 monoclonal antibody on spondyloarthritis mouse model.Methods: A mouse model of spondyloarthritis was established.After the onset of peripheral arthritis,the mice were divided into two pairing groups according to the peripheral arthritis score.For the CCN1 monoclonal antibody group,200 ug 093G9 was injected intraperitoneally three times a week.For the control group,the same doses of Ig G was injected intraperitoneally at the same frequency.The expression of TNF-?,CCN1 and BMP-2 in the lumbar spine from spondyloarthritis model after the treatment of CCN1 monoclonal antibody or control IgG was compared.Results: The peripheral arthritis scores(mean 2.778 ± 1.277;median 2.5)were significantly decreased after the second injection of CCN1 monoclonal antibody;while the mean score in control Ig G group was 4.222 ± 2.063(median 4),p<0.05.The differences in arthritis scores between the two groups were most notable after the eighth injection(p<0.01).The mean scores were 2.000 ± 1.920(median 2)and 5.333 ± 2.046(median 6),respectively.The inflammation and new bone formation of ankle and knee joints were more severe in Ig G control group than 093G9 group.The lumbar intervertebral discs destruction combined with early chondrocyte formation in the 093G9 treatment group was rarer than that in the Ig G group.Conclusion:CCN1 monoclonal antibody therapy can improve the inflammation and new bone formation of spondyloarthritis mouse model.