Oxidized low density lipoprotein promotes proliferation and mRNA expression of inflammatory factors in fibroblast like synoviocytes of rheumatoid arthritis / 中华风湿病学杂志

Objective:To investigate the effects of oxidized low density lipoprotein (Ox-LDL) on cell proliferation and mRNA expression of inflammatory factors in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Methods:Tissue culture was used to isolate and 4-6 generation cultured RA-FLS cells were used for subsequent experiments. RA-FLS were stimulated for 24 hours with different con-centr-ations of human Ox-LDL, then the MTS cell proliferation and toxicity test kit were used to detect the prolifer-ation of RA-FLS. Real time-polymerase chain reaction (RT-PCR) was used to test the expression of inflamm- atory factors like interleukin (IL)-6, transforming growth factor (TGF)-β, IL-8, tumor necrosis factor (TNF)-α and receptors like CD36 and scavenger receptor binds phosphatidylsed neoxidized lipoprotein (SR-PSOX) inRA-FLS. T test and F test were used in this study. Results:Ox-LDL (10, 25, 50 μg/ml) could obviously promote the proliferation of RA-FLS, and theabsorbance values (490 nm) were (1.04±0.15), (1.05±0.14), and (1.00±0.10), respectively, all higher than the control group (0.81±0.04) and the difference was statistically significant ( F=4.737, P<0.01). In addition, 50 μg/ml and 100 μg/ml Ox-LDL also promoted the expression of IL-6 mRNA ( F=14.709, P<0.01) and inhi-bited the expression of TGF-β mRNA ( F=299.074, P<0.01), but there was no obvious effect on the expression of IL-8 and TNF-α. Ox-LDL stimulation could obviously promote the expression of SR-PSOX receptor on RA-FLS ( F=68.636, P<0.01) and inhibit the expression of CD36( F=18.085, P<0.01). After the transfection of siRNA, SR-PSOX mRNA level was significantly inhibited and the mRNA expression of IL-6 was significantly decreased after Ox-LDL stimulation of RA-FLS ( t=3.875, P<0.01), while TGF-β mRNA expres-sion was not significantly changed( t=-0.193, P>0.05). Conclusion:Ox-LDL may play a role in promoting the activation of RA-FLS proliferation and the expression of IL-6 mRNA by increasing the SR-PSOX receptor of RA-FLS, suggesting that Ox-LDL is involved in the synovial inflammation of RA.

Patterns of tocilizumab use in clinical practice of rheumatoid arthritis: a multi-center, non-interventional study in China / 中华风湿病学杂志

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

Clinical analysis of bone mineral density in patients with newly diagnosed untreated systemic lupus erythematous / 中华风湿病学杂志

Objective:The study was aimed to investigate the bone mineral density (BMD) status of newly diagnosed systemic lupus erythematous (SLE) patients.Methods:Newly diagnosed SLE patients and healthy controls in Peking University Third Hospital from 2014 to 2018 were enrolled into this cross-sectional study. Medical records including systemic lupus erythematosus disease activity index (SLEDAI)-2000 and BMD of the lumbar vertebrae and hips measured by dual-energy X-ray absorptiometry were collected. Patients were divided into normal and low BMD groups. Parameters were compared by Student- t test, Mann-Whitney U test and χ 2 test. Results:Eighty-nine patients and 20 healthy controls were included. Approximately 52.8% of the SLE patients had low BMD. Compared to the healthy control group, the BMD of lumbar spine and hip was obviously lower than in the newly diagnosed SLE group[(0.97±0.14) g/cm 2, (1.08±0.10) g/cm 2, t=3.548, P<0.01; (0.88±0.15) g/cm 2, (1.00±0.08) g/cm 2, t=3.878, P<0.01]. The BMD of lumbar spine and hip in the low BMD group was lower than that in the normal BMD group [(0.88±0.10) g/cm 2, (0.80±0.11) g/cm 2; (1.07±0.11) g/cm 2, (0.97±0.13) g/cm 2, respectively]. Compared with the normal BMD group, the body mass index (BMI) was significantly lower [(19.2±2.0) kg/m 2, (23.2±3.6) kg/m 2 respectively, t=3.678, P<0.01], the disease duration was longer [(45.7±7.7) weeks, (16.0±19.5) weeks, respectively, t=-3.306, P<0.01). Patients with low BMD tended to have lower 25-hydroxy-vitamin-D(25-OH-VD 3) level and higher bone metabolism marker levels (Degradation products of collagen B) [(9±5) nmol/L vs (12±7) nmol/L, t=1.385, P>0.05; 0.62(0.21, 1.61) ng/ml vs 0.43(0.19, 0.88) ng/ml, Z=0.624, P>0.05], although their differences didn't reach the statistical significant difference. Conclusion:Newly diagnosed SLE patients' BMD is lower than the healthy people. About 52.8% newly diagnosed untreated SLE patients have low BMD. Lower BMI and longer disease duration are their clinical characteristics. High bone metabolism marker levels, low 25-hydroxy-vitamin-D level might have clinical significance, although the current findings do not find statistically significant difference. Large sample size is required for subsequent research analysis.

Review and analysis on knockout mouse models with cataract / 中华实验眼科杂志

Cataract is the leading cause of blindness worldwide, which is a generally clinical and genetic heterogeneity eye disease.To date, more than 50 genes have been reported to be associated with congenital cataract.While for mouse, parts of human cataract related genes knockout mouse can also resulted cataract.As we know, the model of cataract related gene knockout mice can help us to understand the phenotype, pathogenesis, progress and prognosis of human cataract and it can also help to find unknow genes that not reported in human cataract yet.In this review, knockout mouse models with cataract are summarized, which can help to facilitate identification of cataract genes and clarification of the mechanisms of cataractgenisis.

Expression and significance of miRNA-31 in peripheral blood mononuclear cells of rheumatoid arthritis patients / 中华风湿病学杂志

Objective To investigate the expression of miRNA-31 in peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients,and the relationship between miRNA-31 and disease activity of RA.Methods After obtaining the informed consent,peripheral blood samples of 56 RA patients,12 systemic lupus erythematosus (SLE) patients,6 Sj(o)gren's syndrome (SS) patients and 30 healthy controls were collected from the Department of Rheumatology,Peking University Third Hospital.RNA was extracted from the PBMCs which were separated by Ficoll-Paque PLUS.The expression of miRNA-31 in the PBMCs of RA patients,SLE patients,SS patients and healthy controls was detected by real-time Polymerase Chain Reaction (PCR).Furthermore,according to the RA disease activity score (DAS28),RA patients were divided into high,moderate and low disease activity groups and remission group,and miRNA-31 expression was compared between different groups.Data were analyzed using t test or Mann-Whitney U test.Results The expression of miRNA-31 in PBMCs of RA patients was 7.25 times (P=0.003 8) higher when compared with that of the control group.To be specific,the expression of miRNA-31 was 10.63 times in PBMCs of high activity RA group (P=0.01) and 8.95 times in moderate activity RA group (P=0.000 3) when compared with that of the control group,and there was no significant difference between low activity,remission groups and control groups in terms of miRNA-31 expression.Furthermore,the expression of miRNA-31 in PBMCs of SLE patients was not significantly different from the control and miRNA-31 expression in PBMCs of SS patients was 1.64 times (P=0.02) higher than that of the RA patients,but the average level of miRNA-31 was much less than that of RA patients.The increased miRNA-31 may serve as a diagnostic marker for disease activity of RA.

The expression of oxidized low density lipoprotein and scavenger receptor that binds phospha-tidylserine and oxidized lipoprotein in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the expression level of oxidized low density lipoprotein (ox-LDL) and its scavenger receptor scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SRPSOX) in patients with rheumatoid arthritis (RA),and to explore the relationship between ox-LDL and disease activity.Methods The serum ox-LDL in RA patients and healthy control group were detected by enzymelinked immunosorbent assay (ELISA),as well as the fluidox-LDL in RA,osteoarthritis (OA) and inflammatory arthritis (IA).The expression of SR-PSOX in mixed cells of RA and IApatients was detected by western blot.The expression of serum ox-LDL between RA groupand the control group was analyzed by t-test and non-parametric test.The correlation of serum ox-LDL expression levels in RA patients with C-reactive protein (CRP),erythrocyte sedimentation rate (ESR) and other inflammatory factors and disease activitywas analyzed by Pearson linear regression.Results The expression of ox-LDL in the serum of RA patients was significantly higher than that of normal control group [(3 076±131) mU/ml,(2 334±84) mU/ml,t=4.242,P＜0.01].The expression of ox-LDL in synovial fluid of RA patients was significantly higher than that of the OA group [(4 963±354) mU/ml],(3 956±347) mU/ml,t=2.372,P＜0.05).The expression of SR-PSOX in synovial fluid mixed cells of RA patients was higher than that of the IA group [(4.92±0.18) vs (0.24±0.04),t=33.53,P＜0.01].The expression of ox-LDL in serum of RA patients was negatively correlated with ESR,CRP and overall disease activity DAS28 (r=-9.42,P=0.009;r=-0.35,P=0.029 7;r=0.42,P=0.008 4).The expression of ox-LDL in the serum of RA patients with moderate disease activity was significantly higher than those patients with high disease activity [(3 302±138) mU/ml vs (2 464±228) mU/ml,t=3.335,P＜0.01],however,those with low disease activity and disease remission had higher serum ox-LDL expression but without statistical significant differences.After treated with anti-rheumatic drugs (DMARDs),serum ox-LDL of RA patients had a trend of slight increasing butwithout sign-ificant difference.The ox-LDL/LDL-C or ox-LDL/HDL-C was negatively not correlated with disease activity score in 28 (DAS28),ESR,CRP.Conclusion In RA patients,the expression of ox-LDL in the serum and synovial fluid is high and the SR-PSOX expressionin synovial fluid is also high.The serum ox-LDL levels are negatively correlated with ESR,CRP and DAS28,which are related to disease activity of RA.These findings suggest that the ox-LDL and the receptor SR-PSOX may play a role in RA pathogenesis,but needs further study.

Chemokine axis CXCL16/CXCR6 in the progression of fibrosis / 中华微生物学和免疫学杂志

Fibrosis is the common pathological basis of various lesions. It is mainly manifested as excess collagen deposition and fibrous connective tissue in tissues with destructed structures and impaired function. At present, the pathogenesis of fibrosis is still unclear, and no effective treatment or prevention for fibrosis is available. In recent years, numerous studies have shown that chemokine CXCL16 and its receptor CXCR6 play an important role in the development of fibrosis. This paper summarizes the biological character-istics of CXCL16/CXCR6 axis and its role in fibrosis.

Clinical analysis of the neurological involvement in primary Sj(o)gren's syndrome / 中华风湿病学杂志

Objective To analyze the clinical and laboratory manifestations of primary Sj(o)gren's syndrom (pSS) with neurological involvement.Methods One hundred and forty eight patients fulfilling the 2002 American-European pSS classification criteria were retrospectively analyzed.Neurological manifestations were diagnosed based on the clinical,biological,electrophysiological,and imaging findings.Biographical,clinical,and laboratory data were compared between patients with and without neurological manifestations.Statistical methods used were Mann-Whitney U test,Chi-square test and Fisher exact probability.Results The prevalence of neurological involvement in pSS was 20.3％ (30/148),and the incidence of peripheral neuropathy,the central neuropathy and combination of the central neuropathy with peripheral neuropathy were 10.1％(15/148),9.5％(14/148) and 0.7％(1/148),respectively.The clinical spectrum of peripheral neuropathies encountered in Sj(o)gren's syndrome (SS) patients varied,with the pure sensory neuropathies being the most common,followed by sensorimotor neurophathies.Motor neuron disease was the most common type of central neurophathies.Compared with those without neurological manifestations,the duration of peripheral nerve system/central nerve system (PNS/CNS)-pSS patients was relatively short [(55±76) months vs (100±108) months,Z=-2.682,P＜0.05],and the antinuclear antibody (ANA) titer and RF titer were lower [(234±248) vs (377±339),Z=-2.008,P＜0.05;(126±279) U/ml vs (359±1 445) U/ml,Z=-2.243,P＜0.05].In PNS/CNS-pSS patients,the most common clinical manifestations included numbness (50％),pain (23％),and muscle weakness (63％).Conclusion The prevalence of neurological involvement in pSS is high.The duration is relatively short and the disease activity is high,but the disease features are atypical and may be neglected by rheumatologists.

Expression of CXCL16 /CXCR6 in fibroblast-like synoviocytes in rheumatoid arthritis and its role in synoviocyte proliferation / 北京大学学报(医学版)

Objective:It has been found that serum CXCL16 concentration in rheumatoid arthritis (RA) patients are significantly higher than those in osteoarthritis (OA) and normal subjects, and are positively correlated with disease activity and bone erosion.However, how is CXCL16 involved in the pathogenesis of RA is unclear.To evaluate the expression of CXCL16 and its receptor CXCR6 in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients, and to explore the role of CXCL16 in the proliferation of RA-FLS.Methods: FLS were isolated from knee synovial tissues obtained from 8 patients of RA, 7 osteoarthritis (OA) and 3 normal controls.The diagnosis of RA was in line with the 1987 American Rheumatology Association (ACR) RA classification criteria, osteoarthritis met the 1996 ACR revised knee osteoarthritis classification criteria.Control synovium were obtained from trauma caused knee joint injury in healthy individuals who required surgery.Human knee FLS were cultured by tissue explants adherent method.FLS between passages 3 and 5 were used in the experiment.Expression of CXCL16 and its receptor CXCR6 were performed in Western blot analysis.FLS proliferation follo-wing stimulation with TNF-α and different concentrations of CXCL16 was examined by cell counting kit-8 (CCK-8).Expression of phosphorylated AKT (pAKT) in RA-FLS stimulated by CXCL16 was quantified by Western blot.Different concentrations of recombinant human CXCL16 were added to the culture medium of RA-FLS.After 48 h culture, supernantants were collected, and TNF-α, IL-6, RANKL and MMP3 in culture supernatants of RA-FLS were determined by enzyme-linked immunosorbent assays (ELISA) operated following the kit instructions.Results: Expression of CXCL16 and CXCR6 in RA-FLS was significantly higher than that of OA and controls (P<0.05), but no significant difference was found between OA-FLS and control FLS.Proliferation of RA-FLS was markedly up-regulated after stimulation of CXCL16 (P <0.05).In the case of the CXCL16 stimulated OA-FLS and control FLS, the FLS proliferation remained basically unchanged.Expression of phosphorylated AKT in RA-FLS increased remarkably in condition of CXCL16 (50,100, 200 μg/L) stimulation.The levels of IL-6 and RANKL in culture supernatants of RA-FLS were obviously increased under CXCL16 (200 μg/L) stimulation, while TNF-α and MMP-3 levels in the culture supernatants remained unchanged after CXCL16 (200 μg/L) stimulation.Conclusion: This study shows that the expression of CXCL16 and its receptor was highly elevated in RA-FLS.Recombinant CXCL16 promoted RA-FLS proliferation and activation in vitro.All these indicate that CXCL16 play an important role in the pathogenesis of RA, anti-CXCL16 treatment may help to relieve inflammation and bone damage of RA patients.However, due to the limitations of this study, the role of CXCL16 and its receptors in RA-FLS remains to be elucidated by further research.

Clinical analysis of patients with systemic lupus erythematosus accompanied by cytomegalovirus infection / 中华风湿病学杂志

Objective To analyze the prevalence and clinical features of cytomegalovirus (CMV)infection in patients with systemic lupus erythematosus (SLE).Methods Patients with SLE in Peking University Third Hospital from 2013 to 2015 and age and sex matched healthy controls were enrolled.All patients were detected for CMV antibody,CMV DNA and CMV PP65 in the blood.The prevalence of CMV infection and the clinical characteristics were analyzed using Chi-square test.Results Altogether 349 SLE patients and 209 healthy controls were enrolled.In SLE group,the positive rate of CMV IgG was 90.3％ (315/349),which was similar to that of the control group,while the positive rate of CMV IgM was 8.0％ (28/349),which wassignificantly higher than controls 1.4％(3/209) (x2=10.811,P=0.001),and the active CMV infection rate was 69.1％(241/349).Those in the active phase of SLE were more likely to have active CMV infection when compared with those in remission [75.4％(93/256) vs 51.6％(48/93),x2=18.049,P＜0.01].The percentage [43.2％(104/241)] of severe patients in those with active CMV infection was much higher than that in those without CMV infection 9.2％(10/108) (x2=38.953,P＜0.01).Those SLE patients had active CMV infection were clinically more severe and the most common clinical manifestation were proteinuria/hemoturia,cytopenia and fever.Conclusion In SLE patients,the positive rate of CMV IgM is significantly higher than healthy control and the prevalence of active CMV infection is high,especially in those at active disease.Those with active CMV infection are clinically more severe but have no features of active CMV infection,which indicates that the CMV infection might be a trigger of SLE activity.

A case of arthritis, fever, and hemophagocytic syndrome / 中华风湿病学杂志

Objective To explore the diagnostic and differential diagnostic points of patients with rheumatoid arthritis (RA) complicated with fever.Methods Full clinical analysis was performed for a 62-year old patient with RA and fever.Results Hemophagocytes were found in bone marrows smear.Significantly increased ferritin level (74 299 ng/ml),decreased hemoglobin (67 g/L) and platelet (33×109/L),decreased fibrinogen,increased serum soluble CD25 (sCD25),positive cytomegalovirus (CMV) DNA,positive CMV-PP65 antigen,were found by laboratory examination.Decreased activity of NK cells was detected by flow cytometry.Positron emission computed tomography (PET-CT) revealed splenomegaly and pulmonary inflammations.The clinical conditions were recovered with the treatment of corticosteroid,VP16,cyclosporine,anti-CMV virus therapy.Ferritin level was significantly decreased and platelet was normal.The patient was diagnosed as hemophagocytic syndrome associated with CMV infection.Conclusion The possibility of hemophagocytic syndrome should be considered in RA patients presented with fever.

The preventive effect of diacerein on acute gout model rats / 中华风湿病学杂志

Objective To observe the preventive effect of different doses of diacerein on acute gout model rats and to explore its possible mechanism.Methods A total of 30 Wistar rats and were randomly assigned to the normal control group, the negative control (normal saline control group, and positive (colchicine) control group, diacerein low dose group, medium iddle dose group and high dose group.Except the normal control group that were given normal saline, other groups received colchicine (0.3 mg·kg-1 ·d-1), diacerein (10 mg·kg-1·d-1, 50 mg·kg-1·d-1 and 100 mg·kg-1·d-1) for 8 days respectively, and prepared acute gouty arthritis model on the 6th day, then observed rats joint swelling and gait at 2 h, 6 h, 8 h, 24 h and 48 h after the acute gouty arthritis model were established.After 48 h, the rats were killed, the serum and joint leachate of the rats were collected to test interleukin (IL)-1β and tumor necrosis factor (TNF)-α.One-way analysis of variance (ANOVA), LSD t test and Kruskal-Wallis rank sum test were used for statistical analysis.Results Compared with the normal group, joint swelling of the rats in the negative control group became significantly swollen at 2 h after the model was established,at and it reached the peak at 8 h reached the peak, then decreased gradually and remitted obviously at 48 h obviously remission.Joint swelling of the ccolchicine group and diacerein high dose group joint swelling [(0.106±0.081) cm, (0.112±0.030) cm] and ankle joint inflammation index score [(2.8±1.7), (3.16±0.75)] were significantly decreased compared with the negative control group [(0.208±0.078) cm, (4.7±1.6);P＜0.05].In addition, compared with the negative control group, the gait of diacerein high dose group was significantly improved (F=7.552, F=1.859, P＜0.05), colchieine group and diacerein high dose group, the serum and joint leaching liquid TNF-α and IL-1 levels also decreased significantly (P＜0.05).Conclusion Diacerein in any In each dosage group of has a certain preventive and therapeutic effect on rats gouty arthritis rats, especially in high dose group, the anti-inflammatory mechanism may be down-regulating the expression of proinflammatory mediators such as IL-1 beta and TNF-α.

Clinical and radiographic analysis of patients with cervical subluxations in rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the clinical and radiographic features of rheumatoid arthritis (RA) patients with cervical subluxations.Methods The clinical, laboratory and imaging data of 68 RA patients who were hospitalized to our hospital because of cervical syndrome were retrospectively reviewed.The patients were divided into two groups depend based on whether cervical spine subluxations presented or not.Mann-Whitney U test, t test and Person correlation, x2 test were used for statistical analysis.Results This study confirmed the high frequency (11.6％, 39/335) of radiological cervical subluxations in RA patients.The nNeck pain was a common symptom, accounting for 87％ (34/39).Other symptoms included limb numbness 59％ (23/39).The rate of positive C-reactive protein (CRP) in the subluxation group was both significantly higher than that of the non-subluxation group [89％(24/27) vs 59％(16/27),x2=6.17, P＜0.01].Anterior atlantoaxial subluxation (AAS) was the most common form, accounting for 95％(37/39) of all cervical subluxations,followed by vertical subluxation (VS), accounting for 18％ (7/39).Subaxial subluxation (SAS) of the lower cervical vertebrae was less common (5.1％).The ratio of bone destruction, spinal stenosis, spinal cord compression in image findings of the subluxation group was significantly higher than that of the non-subluxation group (x2=7.96, x2=6.12, x2=4.89, P＜0.05).But more hyperostosis and osteosclerosis feature of the non-subluxation group could be observed more hyperostosis and osteosclerosis feature (x2=6.21, P＜0.05).PADI correlated with ADI (r=-0.588, P=0.015).Conclusion This study confirms the high frequency of radiological cervical involvement in patients with RA.AAS is the most common form of cervical involvement and may occur either independently or concomitantly with cranial settling and subaxial subluxation.

Significance of antibodies of IgG, IgA and IgM isotypes against peptidylarginine deiminase 4 in early rheumatoid arthritis / 中华风湿病学杂志

Objective To evaluate the prevalence and clinical significance of IgG,IgA and IgM isotypes of anti-peptidylarginine deiminase 4 (anti-PAD4) antibodies in early rheumatoid arthritis (RA).Methods IgG,IgA and IgM isotypes of anti-PAD4 antibodies were measured in the sera of 88 RA patients with disease duration less than 2 years,62 patients with other rheumatic diseases and 57 healthy subjects.The diagnostic performance of IgG,IgA and IgM isotypes of anti-PAD4 antibodies and their relationship with disease duration,DAS28,ESR,CRP,anti-CCP antibodies and rheumatoid factor (RF) were evaluated.Data analysis were performed using t test,U test and Spearman's association analysis.Results ① The sensitivities of IgG,IgA,and IgM isotypes for early RA were 28.41％,36.36％ and 9.09％ respectively.The specificities of IgG,IgA and IgM isotypes were 94.12％,93.28％ and 95.80％ respectively.② IgA isotype was positively correlated with age (r=0.234,P=0.028),DAS28 (r=0.309,P=0.007),ESR (r=0.382,P=0.000) and CRP (r=0.291,P=0.008),while negatively correlated with disease duration (r=-0.295,P=0.006).③ IgA isotype was positively correlated with IgG isotype (r=0.451,P＜0.01).In the IgG negative patients,the positivity of IgA isotype was 29％(18/63),which indicated that the IgA isotype might be helpful in diagnosing RA in IgG isotype negative patients.Conclusion Anti-PAD4 antibodies can be detected in early RA,primarily with IgA and IgG isotypes.IgA isotype has negative correlation with disease duration,indicating that IgA isotype of anti-PAD4 antibody may play a role in the very early stage RA.

Detection of BRAF in the synovial fluid and its clinical significance in rheumatoid arthritis / 中华风湿病学杂志

Objective To detect v raf murine sarcoma viral oncogene homologue B1 (BRAF) in the synovial fluid of rheumatoid arthritis (RA) and to investigate its clinical significance in RA.Methods Synovial fluid samples were obtained from patients with RA and osteoarthritis (OA).Serum samples were obtained from patients with RA,OA and heathy controls.The presence of BRAF in the synovial fluid and sera were examined by enzyme-linked immunosorbent assay (ELISA).Western blotting was used to detect the expression of BRAF protein in the synovial tissue of RA and OA.The associations between the BRAF and the clinical features and laboratory parameters of RA were evaluated.Data analysis were performed using t test and Spearman's association analysis.Results ① The level of BRAF in the synovial fluid of RA [(84±59) ng/ml] was significantly higher than OA [(38±41) ng/ml] (t=3.290,P=0.002).② The level of BRAF in the sera of RA patients [(22.0±12.5) ng/ml] was also higher than OA [(6.8±7.5) ng/ml,t=3.882,P＜0.01] and healthy controls [(4.8±2.2) ng/ml,t=6.766,P＜0.01].③ In RA patients,the BRAF protein level in the synovial fluid [(102±52) ng/ml] was significantly higher than that in the serum [(21±12) ng/ml] (t=-4.316,P=0.003).④The expression level of BRAF in the synovial tissue of RA (0.284±0.045) was higher than that in OA patients (0.191±0.013,t=3.169,P=0.034).⑤ The level of BRAF in the synovial fluid had a negative correlation with disease duration (r=-0.40,P=0.019) and a positive correlation with rheumatoid factor (RF) levels (r=0.37,P=0.03).Conclusion The presence of BRAF in the synovial fluid and synovium of RA indicates that BRAF may play a role in the pathogenesis of RA,especially in the early stage.

Significance of antibodies of IgG, IgA and IgM subtypes antibodies against cyclic citrullinated peptide in early rheumatoid arthritis / 中华风湿病学杂志

Objective To evaluate the prevalence and clinical values of anti-cyclic citrullinated peptide (anti-CCP) antibodies of IgG,IgA and IgM subtypes in individuals with early rheumatoid arthritis (RA).Methods IgG,IgA and IgM subtypes of anti-CCP antibodies were measured in the sera of 87 RA patients with disease duration shorter than 2 years,61 patients with other rheumatic diseases and 49 healthy subjects.We analyzed the diagnostic value of IgG,IgA and IgM subtypes of anti-CCP antibodies and their relationship with disease duration,DAS28,ESR,CRP,and rheumatoid factor (RF).Chi-square test,t test and Spearman's correlation analysis were used for statistical analysis.Results ① The diagnostic sensitivity of IgG,and IgA subtype for early RA was 75.9％ and 67.8％ respectively,which was higher than IgM subtype (14％,P＜0.01 each).The specificity of IgG,IgA and IgM subtype was 96.4％,91.8％ and 93.6％ respectively.② IgG and IgA subtypes were correlated with CRP (r=0.278,P=0.01； r=0.217,P=0.047) and RF (r=0.430,P=0.000； r=0.271,P=0.012),while IgM subtype was positively correlated with disease duration (r=0.279,P=0.014).③ Patients who had IgG-and IgA subtype had a shorter disease course (3.3±2.3) than those patients who had IgA-and IgG+ (9.5±8.4) and who had IgG+ and IgA+ (8.2±7.0) (P＜0.05).④ IgA subtype was positive in 19.0％ of the IgG negative patients.When combining IgG,and antibodies of IgA subtypes together,the sensitivity and specificity was 63.2％ and 100％,while the sensitivity and specificity was 80.5％ and 85.2％ when either one was positive.Conclusion Both the IgG,and IgA subtypes of anti-CCP antibodies have a good sensitivity for early RA.They are related to disease activity.Measuring IgA subtype of anti-CCP antibody in RA patients with negative IgG subtype may help to identify early RA.IgA subtype of anti-CCP antibody may play a role in very early RA.

Establishment and evaluation of classification criteria for early rheumatoid arthritis / 中华风湿病学杂志

Objective To establish new classification criteria for early rheumatoid arthritis (E-RA) based on large samples of early inflammatory arthritis patients and to evaluate the value of this criteria in China.Methods Patients who had arthritic complaints with disease duration less than one year were enrolled.They were divided into RA group and non-RA group according to the clinical diagnosis by experienced rheumatologists.The clinical and laboratory parameters were analyzed and those with high sensitivity or specificity were selected as the new classification criteria.Statistical analysis was carried out by using t test,x2 test and Logistic regression.Results ① A total of 803 patients with early inflammatory arthritis were included in this study.Five hundreds and fourteen patients were diagnosed as early RA and 251 were diagnosed as other rheumatic diseases,and the diagnosis of 38 patients remained unestablished by the end of follow-up.② New E-RA classification criteria were established based on the parameters with high sensitivity and/or specificity.The sensitivity of the new E-RA criteria was 84.4％,which was higher than 1987 ACR criteria (58.0％),while the corresponding specificities were similar,which were 87.4％ and 93.6％ respectively.③ Compared with the complex scoring system of 2010 ACR/EULAR criteria,the E-RA criteria was more simple and practical.The diagnostic sensitivity and specificity of E-RA criteria were higher than those of 2010 ACR/EULAR criteria reported in the literatures.④ New classification criteria based on scoring system using Logistic regression analysis was established.The sensitivity of this criteria was 86.4％,which was higher than 1987 ACR criteria (58.0％).Conclusion The diagnostic value of the E-RA criteria developed in this study for early RA is better than 1987 ACR criteria,and is more simple than 2010 ACR/EULAR criteria.It may be used as a new classification criteria for early RA diagnosis.

A multicenter study of fracture in patients with rheumatoid arthritis in China / 中华风湿病学杂志

ObjectiveTo examine the clinical features of fractures and related risk factors in patients with rheumatoid arthritis(RA) in China.MethodsSix hundred and eighty-one RA patients were randomly selected from department of rheumatology of 18 hospitals of China.Data were obtained from the questionnaire,including age,sex,disease duration,the involvement of joints,treatment regimen,features of fractures etc.The possible risk factors of fracture in patients with RA were analyzed with a multi-variate Logistic regression analysis.Results① In 681 RA patients of the survey,48 patients had 54 fractures,and the incidence of fractures was about 8％.② Fractures occurred at various sites.Foot/ankle,femur,spine and wrist were the mostfrequent sites.③ The Logistic regression analysis showed that several factors increased the risk of fracture in RA patients,including long disease duration (OR:1.245,95％CI:0.987-1.570,P=0.065),male gender(OR:0.433,95％CI:0.199-0.942,P=0.035),more deformed joints(OR:1.042,95％CI:1.006-1.079,P=0.023),family history of RA (OR:2.201,95％CI:0.984-4.923,P=0.055),and high scores of SF-36(OR:1.017,95％CI:1.002-1.033,P=0.028).④ According to the degree of correlation from strong to weak,the risk factors of fracture were disease duration,SF-36,sex,number of deformed joints and family history of rheumatoid arthritis.ConclusionThe incidence of fracture is high in patients with rheumatoid arthritis.Several factors could increase the risk of fractures in RA patients,including long disease duration,male gender,more deformed joints,and family history of RA.In order to prevent the occurrence of fractures,cautions should be taken to prevent the development of fractures and treat the disease aggressively to suppress the disease activity of RA.

Expression of chemokine CXCL16 in murine collagen-induced arthritis and the effects on the proliferation of lymphocytes / 中华风湿病学杂志

Objective To investigate the effect of CXCL16 on the development of murine collageninduced arthritis (CIA). Methods CXCL16 mRNA of the involved synovium and serum CXCL16 protein were determined respectively by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA) in murine collagen-induced arthritis. The proliferation of lymphocytes from murine spleen and the level of RANKL mRNA, stimulated by CXCL16 at different concentrations (0,100, 200, 400, 800 ng/ml), was detected respectively by CCK-8 and RT-PCR, then the level of IL-2 and IFN-γ in culture supernatant was detected by ELISA. Comparisons between groups were tested by t test and one-way ANOVA analysis. Results The serum CXCL16 [(127± 10) vs (72±8) pg/ml, P＜0.05] and synovial CXCL16 mRNA (0.214±0.007 vs 0.375±0.009, P＜0.01) in CIA were all significantly higher than those in normal controls. The proliferation of CXCL16 (200, 400, 800 ng/ml) in CIA mouse lymphocytes, was significantly higher than that of CXCL16 (0 ng/ml) (0.51±0.06, 0.56±0.05, 0.55±0.04, (0.41±0.04, P＜0.05). And CXCL16 on the CIA stimulated lymphocyte proliferation was significantly higher than controls on normal lymphocytes (P＜0.05). Compared with blank control group, the expression of IL-2, IFN-γ and RANKL mRNA of CIA CXCL16 (400, 800 ng/ml) groups was higher significantly (P＜0.01). Conclusion CXCL16 plays an important role in the development of murine CIA by activating lymphocytes.

The clinical significance of anti-nuclear protein B23 in systemic sclerosis / 中华风湿病学杂志

Objective To explore the clinical significance of anti-nuclear protein B23 antibody in systemic sclerosis. Methods Enzyme-linked immunosorbent assay was employed to detect the serum antinuclear B23 autoantibody. Mann-Whitney U test was used to compare the clinical and autoantibody profiles between SSc patients with B23 antibody and those without B23 antibody. Logistic regression analysis was employed to analyze the correlation between B23 antibody and clinical manifestations and autoantibody profiles. Results Mann-Whitney U test showed that, forced vital capacity (FVC) diffusion capacity of CO (DLco) in B23 positive SSc was significantly lower than that in B23 negative counterparts, pulmonary artery hypertension was more prevalent in B23 positive SSc patients. While anti-fibrillarin, anti-U1RNP, and antic entromere antibodies were more prevalent in B23 positive SSc. Multivariate logistic regression showed that anti-B23 antibody positivity was an independent risk factor for pulmonary artery hypertension in SSc (OR=123.92, 95％CI 26.67～575.66, P＜0.01), and a protective factor for severe gastrointestinal involvement (OR=0.08, 95％CI 0.01 ～0.70, P＜O.05). Logistic analysis showed that anti-B23 antibody was correlated with antifibrillarin (OR=11.50, 95％CI3.85～34.37, P＜0.01) and anti-U1RNP antibodies (OR=3.43, 95％CI 1.01～11.63, P＜0.05), and correlated with different degree of pulmonary artery hypertension. Conclusion The pulmonary artery pressure should be monitored closely in those SSc patients with a positive B23 antibody.