Objective To explore the clinical,laboratory,and pathologic manifestations of the interstitial lung disease(ILD)associated with primary Sj(o)gren's syndrome(pSS,pSS-ILD).Methods Clinical data of 15 patients with pSS-ILD admitted to our hospital from 2006 to 2008 were collected and the different features were compared with 18 patients with pSS without ILD.Eight patients with pSS-ILD were followed up and observed the changes of high-resolution computed tomography (HRCT).Results The age at onset was later in pSS-ILD[(57±11)years]than in pSS without ILD[(43±11)years](P<0.01).The initial symptoms in six of patients with pSS-ILD were cough,expectoration,chest distress or dyspnea upon exertion.The respiratory clinical manifestations,circulationsystem involvement and pulmonary artery hypertension (PAH) were more common in pSS-ILD than in pSS without ILD(P<0.01).Compared with patients with pSS without ILD,patients with pSS-ILD had significantly higher serum IgG level(P<0.01).The common findings of HRCT included reticular changes,irregular linear hyper-attenuating areas,and nodules.Pleural involvement was found in 8 patients,honeycomb change in 5 patients and PAH in 3 patients.After treated for 6 months of 8 patients,radiological findings improved in 4 patients,stable in 2 patients,and worse in 2 patients.The comlnon histological findings included focal fibrosis in alveolar wall and alveolus with and alveolar space inflammatory cell infiltration,interstitial inflammation with mulifocal lymphocyte infiltration.One patient had the pathological changes of nonspecific interstitial pneumonia(NSIP).Conclusion The age at onset of pSS-ILD is late and tends to produce respiratory symptoms and prone to have circulationsystem involvement such as PAH and elevated serum IgG level.Honeycomb change in HRCT can be seen in one third of patients and most patients can improve after treatment,however.NSIP can be observed in histopathologieal

Objective To investigate the serum concentration of interleukin (IL)-17 in patients with active rheumatoid arthritis and the clinical implication. Methods Serum IL-17 level of 51 active RA patients were assessed by enzyme-linked immunosorbentassay (ELISA). The relationship between serum levels of IL-17 in active RA patients and clinic features were analyzed. Two independent samples t test, ANOVA for repeated, one-way ANOVA and Spearman's Chi-square test were used for statistical analysis. Results ① Serum IL-17 levels were elevated in active RA patients (365±63) pg/ml than in normal controls (86±13) pg/ml (P<0.01); ② Serum IL-17 levels in active RA was correlated with morning stiffiness duration, swelling index, Ritchie index, CRP, ESR, RF, X-ray score, DAS score (r =0.423, 0.213, 0.252, 0.276, 0.346, 0.251, 0.412, 0.398; P<0.05). ③ The levels of IL-17 between phase I (296±79) pg/ml and Phase II (360±89) pg/ml, phase II and phase HI (464±74) pg/ml, Phase I and Phase Ⅳ (369±83) pg/ml in RA group were statistically significantly different (P<0.05). Conclusion The levels of serum IL-17 in active RA patients are higher than the normal controls. The elevated serum IL-17 levels may be the useful markers for active RA.In addition,interleukin-17 is involved in disease progression and bony erosion of RA, and it maybe a new treatmenttarget of RA.

Objective We investigated interleukin (IL)-23 that might play a role in the pathogenesis of rheumatoid arthritis (RA) and whether it was correlated with disease activity and clinical manifestations in axial spondyloarthritis (SPA).In addition, the Spondyloarthritis Research Consortium of Canada (SPARCC) scores was used to examine whether recombinant human tumor necrosis factor-α receptor Ⅱ IgG Fc fusion protein for injection (rhTNFR:Fc) was effective for the reduction of magnetic resonance imaging (MRI)-proven sacroiliac joint (SIJ) inflammation.Methods The serum IL-23 levels of etanercept and conven-tional treatment groups were measured using enzyme-linked immunosorbent assay kits.At the same time, SIJ MRI SPARCC score levels were assessed by MRI, the change of clinical indicators of patients was observed.ANOVA, repeated measure data of ANOVA and Spearman's correlation analysis were used for statisical analysis.Results ① The basal serum IL-23 levels of the Etanercept group were (34.2±1.8) pg/ml and those of the conventional treatment group were (34.1 ±1.8) pg/ml (F=1 073.790, P=0.991), both were significantly higher than the healthy control group (18.1±0.8) pg/ml (P=0.005).After treatment, serum IL-23 levels of the rhTNFR: Fc treatment and conventional treatment group were (24.5 ±1.7) pg/ml and (25.2±1.7) pg/ml (F=232.488, P=0.242), (19.2±0.8) pg/ml and (21.6±1.3) pg/ml (F=114.135, P=0.025), (19.0±0.8) pg/ml and(19.4± 0.8) pg/ml (F=23.374, P=0.085) respectively.A significant decrease was observed in the two groups and the serum level of IL-23 of the rhTNFR:Fc group was lower than that of the conventional group at week 12.② SIJ MRI SPARCC scores of the rhTNFR:Fc group and the conventional drugs group were (20.1± 1.2) scores and(20.7±1.5) scores (F=2003.660, P=0.191), (12.5± 0.8) scores and (15.4±0.9) scores (F=1 680.430, P=0.004), (8.8±0.9) scores and (12.8± 0.9) scores (F=972.877, P=0.002), the scores of two group were significantly decreased after treatment.At week 12, 24 of the treatment, the rhTNFR:Fc group scores were lower than the conventional drugs group.③ The serum IL-23 levels, SLJ MRI SPARCC scores and clinical index (ESR, CRP, PGA, BASDAI, BASFI, BASMI and number of painful joints) were not correlated (P＞0.05), the SIJ MRI SPARCC scores and clinical indicators were not correlated (P＞0.05).Conclusion ① The serum IL-23 levels of the rhTNFR:Fc are higher than healthy controls.② rhTNFR:Fc treatment could significantly decrease IL-23 levels and improve the sacroiliac joint inflammation compared to conventional treatment.③ SIJ MRI is a good assessment method for the detection of SpA sacroiliac joint inflammation.

Objective To study the expression and significance of Th17 and Tc17 cells in the peripheral blood,skin and lung in a murine model of bleomycin (BLM)-induced systemic sclerosis (SSc).Methods Thirty female BALB/c mouse were randomly divided into 3 groups,including a control group ( A group),a injected with BLM 4 week without pulmonary fibrosis(PF) group( B group) and with obviously PF group(C group).Pathological changes of skin and lung were detected.The proportion of CD4+,CD8+,CD4+IL-17+(Th17),CD8+IL-17+(Tc17) cells in the peripheral blood,skin and lung of mouse was determined by flow cytometry.The mRNA expressions of RORγt,IL-17A in skin and lung of mouse were evaluated by real-time PCR.Enzyme linked immunosorbent assay(ELISA) was used to measure the levels of IL-17 in serum.Results Dermal hydroxyproline(HYP) contents and the score of PF were significantly increased in C group [ (3.07±1.26) μg/mg,4.0±1.41 ]and B group [ (2.43±0.61) μμg/mg,1.50±0.76]as compared with A group [ (1.45±0.40) μg/mg,0.60±0.70 ],and pulmonary HYP contents was obviously increased in C group than in A and B groups,all P＜0.05.Compared with the A group,the percentage of CD4+ and Th17 cells in the peripheral blood,skin and lung of B and C groups,Tc17 cells of C group was significantly increased,and CD8+ cells was significantly decreased(all P＜0.05).The ratio of Th17/CD4+CD8+ in the peripheral blood,skin and lung of B and C groups [ ( 1.41 ±0.36)％,( 1.79±0.77)％ ],[ (2.58±1.07)％,(5.23±2.34)％ ]and [ (3.50±1.20)％,(4.02±1.32) ％ ]was significantly increased compared with A group (0.71±0.25)％,(1.15±0.59)％,(0.99±0.46)％.The ratio of Tc17/CD4+CD8+ in the lung of C groups( 1.62±0.53) ％ and in the skin of B and C groups [ (1.70±0.70) ％,( 1.63±0.63 ) ％ ]was significantly increased compared with A group [ ( 1.00±0.47 ) ％,( 1.1 1 ±0.34 ) ％ ],all P＜0.05.Compared with the A group,the mRNA levels of IL-17A,RORγt in skin of B and C groups,and in lung of C group were higher and the levels of IL-17 in serum was significantly increased,all P＜0.05.Th17 cells and the levels of IL-17 in blood were positive correlation with dermal and pulmonary inflammation,fibrosis and H YP contents,all P＜0.01.The frequency of Th17 and Tc17 cells in skin and lung respectively had a positive correlation with dermal and pulmonary inflammation,the score of fibrosis,and HYP contents of skin and lung,all P＜0.01.Conclusion Th17 and Tc17 cells were significantly increased in the peripheral blood,skin and lung of a murine model of SSc,and Th17 cells is dominated.They correlated with the inflammation and fibrosis of skin and lung,and may participate in the pathogenesis of SSc through secrete IL-17.

ObjectiveTo investigate the changes of high resolution computerized tomography (HRCT) of chest and quality of life and the main correlated factors of HRCT for interstitial lung disease(ILD) in patients with rheumatoid arthritis(RA).MethodsTwenty-six initial treatment patients with RA-ILD were enrolled.The following parameters were noted at baseline,12 and24 weeks for each patient:clinical features,HRCT,quality of life.ANOVA was used for repeated measurement data and stepwise multiple regression analysis were used to analyze the relativity between HRCT and other parameters.ResultsTwentysix patients were included.Twelve male(46％) patients were followed up for 24 weeks and pulmonary infection occurred in 11 patients,so the frequency rate was 42％.After being treated with prednisone and cyclophosphamide for 24 weeks,the HRCT scores were lower than before [(8+6) vs(12±5),respectively] and 16 patients' condition were improved,6 were in stable and 4 had deteriorated disease.For quality of life,the impact scores,symptom scores,activity scores,and total scores of St.George's respiratory questionnaire (SGRQ) were significantly decreased(F=3.783,6.362,4.217,4.426,P＜0.05) and all domains of the short form-36 health survey questionnaire(SF-36) had significant improvement after treatment.Stepwise multiple regression analysis showed that the impact scores(P=0.000) and symptom scores(P=0.001) of SGRQ,vitality (P=0.012) of questionnaire,globulin (P=0.027) in prior treatment and symptom scores (P--0.001 ) of SGRQ,course of disease (P=0.002),MRC score (P=0.011),vitality (P=0.036) of SF-36 questionnaire in post-treatment were the main correlated factors with HRCT features.ConclusionMale RA patients are prone to develop ILD and RA-ILD is susceptible to pulmonary infection.After early treatment,HRCT and quality of life in most patients can be improved.Respiratory symptoms,severity of dyspnea,globulin level,course of disease and vitality of patients are significantly correlated with HRCT.

Objective To investigate the serum concentration of vascular endothelial growth factor (VEGF) and its soluble receptor 1 (sFlt-1) in patients with systemic lupus erythematosus (SLE) and its correlation with clinic and pathologic parameters.Methods serum levels of VEGF and sFlt-1 in a group of 60 patients with SLE and 30 healthy controls were assessed by ELISA.Results The VEGF and sFlt-1 serum levels were higher in active SLE group than the control group (P＜0.01).The VEGF/sFlt-1 ratio in the control group was lower than that in the active SLE group.inactive SLE group and LN group (P＜0.01).Particularly the ratio increased in WHO class Ⅴ LN group compared to WHO classⅡ,Ⅲ,Ⅳ LN group (P＜0.05).The semm level of sFlt-1 was correlated to proteinuria (rs=0.6244,P＜0.01) and ESR (rs=0.4235,P＜0.01) and the serum levels of VEGF and sFlt-1 were correlated to the systemic lupus erythematosus disease activation index (SLEDAI) (rs=0.5046,P＜0.01 and rs=0.5152,P＜0.01,respectively).The serum level of VEGF was correlated with renal tissue activation index (RAI) (rs=0.3386.P＜0.05) and the serum levels of VEGF and sFlt-1 were not correlated to blood pressure,serum creatine,blood ureanitmgen,C3,C4,C-reative protein.The muhi-factors stepwise regression analysis indicated that serum VEGF was positively correlated with SLEDAI (R2=0.1 75,P＜0.05),serum sFlt-1 was positively correlated with ESR and proteinurine (R2=0.497,P＜0.05).Conclusion Serum VEGF and sFlt-1 are elevated in patients with active SLE and they can reflect the activity of the disease.The overcxpression of serum VEGF might be correlated to the proliferated glomerulonephritis and the overexpression of sFlt-1 contribhtes to proteinurla.The imbalance between these two factors may act an important role in SLE pathogenesis.

Objective To study the phenotype and function of CD4 +CD25 + Treg cells in the peripheral blood of patients with systemic sclerosis (SSc) and their relationship with fibrosis.Methods The proportion of Foxp3, CD127, CTLA-4 and CD69 on CD4+CD25+ Treg cells in peripheral blood were detect by flow cytometry;the levels of TGF-[1 and IL-10 in serum were detect by enzyme-linked immunosorbent assay (ELISA) in patients with SSc.The correlation between Treg cells and the score of chest HRCT, MRSS, and disease activity was analyzed.T test and Pearson correlation analysis were used for statistical analysis.Results ① Compare to the control group, the proportion of CD4+CD25+ Treg cells in peripheral blood of SSc patients was increased significantly(12.9±2.4 vs 14.9±2.2, t=2.63, P=-0.012), and the expression of CD69+, CTLA-4+ on CD4+CD25+ Treg cells was decreased significantly (P＜0.01).② Compare to the control group, the proportion of CD4+CD25+Foxp3 + cells and CD4+CD25+CDI27-cells in peripheral blood of SSc patients was increased significantly (respectively, 3.3±0.7 vs 5.0±0.7, 5.1±1.6 vs 7.6±2.0, t=7.03, 4.195;P＜0.01), but no correlation between them was detected.③ The level of TGF-β1 in the serum of the SSc patients was lower than that of the control group(86±29 vs 133±29 ng/ml, t=-5.026, P=0.000).However, IL-10 had no significant difference between the two groups.④ The proportion of CD4+CD25 +Foxp3 + cells and CD4~D25 +CD127-cells in peripheral blood of SSc patients was positively correlated with the scores of chest HRCT (respectively, r=-0.541, P=0.02;r=0.486, P=0.041), and no correlation was observed with ESR, CRP.In addition, CD4+CD25+Foxp3+ cells were associated with MRSS.Conclusion The proportion of CD4+CD25+ Treg cells in the peripheral blood of SSc patients is increased, but they alters the immune function.The different phenotypes of Treg cells of CD4+CD25+Foxp3+ cells and CD4+CD25+CD127-cells in peripheral blood of SSc patients are increased significantly, which changes along with skin and lung fibrosis.The associated cytokine TGF-β1 is reduced, and IL-10 is not significantly changed.

Objective: To analyze the correlation between the Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) sacroiliac joint inflammation score (SPARCC score)/structural score (SSS) and the disease activity as well as the functional indexs. The correlation between the MRI score and inflammatory indicators [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] in patients with active axial spondyloarthritis (axSpA) before and after treatment was explored. In addition, the contribution of the two MRI scoring method in evaluating conditions was also explored. Methods: According to the inclusion criteria, 24 patients with active axial SpA were recruited and received the recombinant hauman tumor necrosis factor (TNF)-α receptor Ⅱ: IgG Fc fusion protein(rhTNFR:Fc), sulfasalazine and thalidomide for 12 weeks. Subjects were scored at week 0 and 12 by SPARCC/SSS scores. Bath ankylosing spondylitis disease activity index (BASDAI), Assessment of Spondyloarthritis Intemational Society (ASAS)-endorsed disease activity score(ASDAS)-CRP, bath ankylosing spondylitis functional index (BASFI). Bath ankylosing spondylitis metrology index(BASMI), ESR and CRP. The correlation between the SPARCC/SSS scores and that of clinical indicators were analyzed. Paired sample t test, Wilcoxon signedrank test, Spearman correlation analysis and Pearson correlation analysis were used for statistical analysis, and receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of SPARCC score decline as a response to treatment. Results: ① Compared with baseline, after 12 weeks treatment, SPARCC scores [(15±4) and(33±10)], BASDAI [(3.2±0.9) and (5.2±1.1)], BASFI [(2.3±0.6) and (4.6±1.0)], BASMI [(2.3±0.7) and (4.1±1.1)], ASDAS-CRP scores [(2.0±0.8) and (3.7±0.9)], ESR [(16±12) mm/1 h and (49±26) mm/1 h], CRP [(7.2±2.8) mg/L and (30.4±19.3) mg/L] were significantly decreased (t values were 7.822, 6.950, 10.707, 7.204, 6.281,-4.015 and-4.257, respectively), and the differences were statistically significant (P=0.000). There was no significant difference in SSS scores between baseline [(20±6) and (19±7)] and after 12 weeks treatment (t=-0.761, P=0.455). ② Before treatment, SPARCC score showed positive linear correlation with BASDAI (r=0.630, P=0.001), ASDAS-CRP (r=0.646, P=0.001), CRP (r=0.574, P=0.003) and ESR (r=0.559, P=0.004), and the correlation of the above indexes disappeared after treatment (P>0.05). The association between SPARCC structral scores and the above indicators was not significant before and after treatment. ③ Areas under curve(AUC) of ROC for assessing treatment response by reduced SPARCC scores was 0.809. The cut-off value for response to treatment was 20.5, with the sensitivity of 68.8% and specificity of 75.0%. Conclusion The SPARCC MRI SIJ inflamm-ation score has certain value in evaluating disease activity and efficacy, while the SPARCC SSS is not.