Effect of miR-124a on collagen-induced arthritis in mice and the underlying mechanisms / 中南大学学报(医学版)

OBJECTIVES@#Rheumatoid arthritis (RA) is a chronic autoimmune disease. MicroRNA has been shown to play an important role in RA. MicroRNA-124a (miR-124a) has anti-proliferative and anti-inflammatory effects in RA fibroblast synovial cells. This study aims to explore the effects of miR-124a overexpression on arthritis in collagen-induced arthritis (CIA) mice and the underlying mechanisms.@*METHODS@#Bovine type II collagen and complete Ferris adjuvant were used to induce CIA model from DBA/1 mice. Twenty-eight days after initial immunization (D28), CIA mice were randomly divided into a model group, a miR-124a treatment group, and a negative control (NC) group. Physiological saline, miR-124a agomir, and miR-124a agomir NC were injected into the skin at the tail root of mice every 3 days for 4 times, respectively. The degree of joint swelling and arthritis index of mice were recorded accordingly. Sixty-three days after initial immunization (D63), the mice were sacrificed to obtain the synovial tissue of ankle joint. HE staining was used to observe the proliferation of synovial cell, infiltration of inflammatory cell, pannus, and bone erosion of synovial tissues; TUNEL staining was used to detect cell apoptosis; qRT-PCR was used to detect the mRNA expression of miR-124a, phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) and its downstream genes Bcl-2 and Bax. Immunohistochemistry was used to detect the protein expression of PIK3CA, Bcl-2, and Bax protein in synovial tissues of each group.@*RESULTS@#Different degrees of swelling presented in the paws of DBA/1 mice at D28, which indicated the CIA model was constructed successfully. Forty-eight days after initial immunization (D48), the paws of mice in the miR-124a treatment group were only slightly red and swollen, while the paws of mice in the model group and the NC group were obviously red and swollen. The arthritis index of mice in the miR-124a treatment group were decreased significantly compared to the NC group at D51, D53, D59, and D62 (51, 53, 59, 62 days after initial immunization) (all P<0.05). Sixty-three days after initial immunization (D63), HE staining indicated that the scores of synovial cell proliferation, inflammatory cell infiltration, synovial pannus, and bone erosion were significantly reduced in the miR-124a treatment group (P<0.05 or P<0.01), while cell apoptosis was increased in the miR-124a treatment group compared with the model group and NC group (P<0.01 or P<0.001). Besides, the expression of miR-124a and Bax in the synovial tissue in miR-124a treatment group was significantly higher than those in the model group and NC group (P<0.01 or P<0.001), while the expressions of PIK3CA and Bcl-2 were decreased (P<0.05 or P<0.01 or P<0.001), and the ratio of Bcl-2 to Bax was significantly decreased (P<0.01 or P<0.001).@*CONCLUSIONS@#Overexpression of miR-124a can reduce arthritis in CIA mice bacause it could promote synovial cell apoptosis and inhibit synovial cell proliferation via targeting PIK3CA and regulating its downstream pathways.

The short-term efficacy and safety of HA280 immunoadsorption column in patients with idiopathic inflammatory myopathies / 中华风湿病学杂志

Objective:To evaluate the short-term efficacy and safety of HA280 immunoadsorption (IA) column in idiopathic inflammatory myopathies (IIM).Methods:The clinical data of 72 patients with IIM admitted to the Department of Rheumatology of Xiangya No.2 Hospital of Central South University from January 2015 to March 2018 were analyzed. Of these patients, 22 patients were treated with HA280 immunoadsorption column for three times (the immunoadsorption group) and 50 patients were treated with drugs only (the control group). The changes of clinical symptoms and signs, autoimmune antibodies, myocardial enzyme spectrum, the inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and ferritin], immunoglobulin, complement, other biochemical indexes and pulmonary images of the patients were detected and analyzed before and after the treatment. And then the data were analyzed by Chi-square test, samples t testand Wilcoxon rank sum test. Results:Compared with the control group, the symptoms and signs were obviously improved after treatment with HA280 immunoadsorption column. In particular, the clinical improvement rate of non-specific myositis (89%, 16/18) was higher than that of the control group [(58%, 22/38), χ2=5.379, P<0.05]. And the clearance of autoantibody (control group) was grade 39.41 in average, 28.38 in average in the immunoadsorption group( Z=-2.51, P=0.01), myocardial enzyme spectrum [control 717(1 564) U/L, immunoadsorption group 126(432) U/L , Z=3.09, P<0.01], the inflammatory markers such as ESR [the control group was 24(22) mm/1 h, the immunoadsorption group was 10(7) mm/1 h, Z=-3.0, P=0.003] and immunoglobulin G [the control group was 11(5) g/L, the immunoadsorption group was 9(2) g/L, Z=-4.8, P=0.001] and immunoglobulin M [the control group was 0.9(0.4) g/L, the immunoadsorption group was 1.2(0.8) g/L, Z=-2.0, P=0.05]. Moreover, the lung CT scan showed that pulmonary lesions of the patients in the immunoadsorption group (89%, 17/19) was much more improved than the control group [(61%, 27/44), χ2=4.98, P<0.05]. No serious adverse reactions occurred. Conclusion:HA280 immunoadsorption therapy can significantly clear the autoantibodies, decrease muscle enzymes, inflammatory markers and immunoglobulin, improve lung images of some patients in a short time. It has been shown that it is safein patients with IIM. HA280 immunoadsorption therapy could be an effective treatment for IIM.

Association of short-term efficacy for infliximab in rheumatoid arthritis with plasma concentration and anti-drug antibody / 中南大学学报(医学版)

To investigate the correlation between peripheral concentration of infliximab (IFX) or anti-IFX antibody titers and short-term therapeutic effect of IFX in patients with active rheumatoid arthritis (RA).
 Methods: Twenty patients with active RA were treated with combination of methotrexate (MTX), leflunomide (LEF) with IFX, and the clinical and laboratory index and the side effects were recorded before and after IFX treatment. Twenty healthy subjects were chosen as a control group.
 Results: After 14-week treatment, patients were categorized into good, moderate or no responders according to EULAR remission criteria. There were no significant differences in peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels among the 3 groups, and there were no significant correlations among ΔDAS28-CRP, peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels.
 Conclusion: Peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels can not be used as reliable predictive index for short-term effect of IFX in active RA.

Clinical effect of tocilizumab on patients with severe active rheumatoid arthritis / 中南大学学报(医学版)

Objective:To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).Methods:Twelve patients with severe refractory RA were treated with tocilizumab.The clinical and laboratory indices and the side effects were recorded after treatment.Results:The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients,which were significantly improved after TCZ therapy (P＜0.05),and no obvious adverse reactions were found.Conclusion:Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.