Objective To determine the prognostic factors in systemic sclerosis.Methods Clinical data of definite systemic sclerosis patients were collected,including disease onset age,sex,disease course,Raynaud's phenomenon,skin involvement,gastroesophageal reflux,interstitial pneumonia,cardiac lesions,kidney lesions and scleroderma renal crisis.serum antibodies to scl-70.RNP and anti-centromere antibody were detected.Pulmonary artery pressure was measured by ultrasound cardiography.Cox hazard ratio model was employed to assess the mortality risk of systemic sclerosis patients.Results No difference in Raynaud's phenomenon,gastroesophageal reflux,anti-nuclear antybody,anti-sol-70 antibody,anti-centromere antibody,interstitial pneumonia,diffusion capacity (DLco),coronary artery disease,and peripheral artery atherosclerotic disease could be found between the dead and alive systemic sclerosis patients(P>0.05).Dead systemic sclerosis patients had later disease,onset(older than 60 years old)(P=0.002).Male gender(P=0.023),more diffuse skin involvement(P=0.000),more positive anti-RNP antibody(P=0.014),more pulmonary artery hypertension(P=0.000).more cardiac lesions(P=0.000),more cerebral infarets (P=0.035),more kidney lesions(P=0.000),and more scleroderma renal crisis(P=0.000) could be found jn dead sclerosis patients.Cox regression analysis showed that,onset later than 60 years old(OR=5.441.95% CI 2.126～13.926,P=0.000),male sex (OR=5.531,95%CI 2.014～15.190,P=0.001),anti-RNP antibedy positivity (OR=2.664,95%CI 1.016～6.592,P=0.034),diffuse skin involvement(OR=3.432,95%CI 1.400～8.411,P=0.007),pulmonary artery hypertension (OR=25.718,95% CI 5.954～111.085,P=0.000),cardiac lesions (OR=4.141.95%CI 1.685～10.159,P=0.002),kidney lesions(OR=4.214,95%CI 1.654～10.737,P=0.003) and scleroderma renal crisis (OR=20.677,95% CI 4.161～102.764.P=0.000)were risk factors for mortality in systemic sclerosis.Severe pulmonary hypertension was the most strong predictive factor for mortality in systemic sclerosis (OR=55.809,95% CI 12.879～241.832.P=0.000).Conclusion Aggressive therapy should be given to those systemic sclerosis patients with onset later than 60 years old,male sex,diffuse skin involvement,anti-RNP antibody positivity,cardiac involvement,kidney lesions,scleroderma renal crisis and pulmonary artery hypertension,especially seevere pulmonary hypertension.

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.

Objectives To assess the presence of autoantibodies directed against the epitopes of SmB and SmD in systemic lupus erythemotosus(SLE) as well as other different connective tissue diseases(CTDs) and analyze the clinical significance of them.Methods Polypeptides of SmB and SmD were designed with the animo acids sequence by the biologic technical software.The sera from different patients including 102 SLE,153 other CTDs and 54 controls were detected by ELISA with thesynthetic polypeptides.Results The positive percentage of anti-SmB and antiSm-D epitopes were higher in SLE than in other groups (P

Objective To investigate the clinical features of primary retroperitoneal fibrosis (RPF), and to find out better method for diagnosis and therapy. Methods Nine patients with primary RPF in Peking Union Medical College Hospital since 1990 to 2003 were analyzed retrospectively. Results All patients had abnormal findings in CT or MRI, and 8 of them had chronic non-specific inflammation of the retroperitoneum in pathology. Six patients had renal involvement and 2 of them had severe renal failure. Eight of the patients had received therapy with corticosteroid or tamoxifene. Conclusions RPF is an uncommon collagen vascular disease characterized by a chronic non-specific inflammation of the retroperitoneum.Because of the atypical manifestations of RPF, awareness of the disease is important.CT and (or) open biopsy remains the gold standard for diagnosis.Management typically includes surgery and drug treatment.Corticosteroid therapy or more recently,tamoxifen has been used successfully. The clinical and radiographic improvement with drug treatment has been seen in several patients and confirmed the diagnosis,thereby early diagnosis and treatment can bring the patient more excellent renal and general outcome.

Objective To investigate the effects of Thalidomide(THD)on transdifferentiation of human fetal lung fibroblast(HFL-F) to myofibroblast(MF) induced by Transforming Growth Factor-?1(TGF-?1) and the effects on trans differentiated MF.Methods HFL-F to MF trans-differentiation was induced with 5 ?g/L TGF-?1.The effect of 50 ?g/L THD on HFL-F to MF transdifferentiation was evaluated by measuring hydroxyproline(HYP) content with alkaline hydrolysis colorimetry,?-smooth muscle actin(?-SMA) protein with Western Blot,?-SMA and collagen Ⅲ(COL Ⅲ) mRNA with semiquantitative RT-PCR.Results THD inhibited TGF-?1 induced up-regulation of HYP and COLⅢ mRNA expressions(all P0.05).For HFL-F treated with 5 ?g/L TGF-?1 for 96 h,THD inhibited COLⅢ mRNA expression(P

Objective To detect anti-heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2)/RA33 antibody by ELISA with the purified recombinant hnRNP A2 antigen. Methods The serum of 179 patients with RA, 141 patients with SLE, 97 patients with other diffused rheumatic diseases, 30 patients with seronegative spondyloarthropathies, 10 patients with osteoarthritis, 59 patients with arthralgia/arthritis and 40 controls were detected. In addition, clinical characters and laboratory indexes were compared to study the significance of anti-hnRNP A2/RA33 antibody in RA. Results The sensitivity and specificity of anti-hnRNP A2/RA33 antibody in RA were 36.9% and 87.1%. The positive rates of anti-hnRNP A2/RA33 antibody in SLE, other CTD, seronegative spondyloarthropathies and OA were 19.2%, 7.2%, 6.8% and 0. The positive rate of anti-hnRNP A2/RA33 antibody was 43.3% in early RA patients. Conclusion Detection of anti- hnRNP A2/RA33 antibody with purified recombinant hnRNP A2 antigen is a reliable method for early diagnosis of RA.

Objective To detect the expression of chemokine receptors CXCR3 mRNA in the peripheral blood mononuclear cells (PBNCs) of patients with Rheumatoid Arthritis (RA) and to analyze the relationship between the expression and the disease activity. Methods mRNA was extracted from PBNCs and the expression of CXCR3 mRNA was detected by real-time fluorescence quantitative PCR (RFQ-PCR) in 51 RA patients and 32 controls. T-test, x2-test, ANOVA were used for statistial analysis. Results Comparison between the two groups had shown that the expression levels of CXCR3 mRNA in clinical active RA group were higher than those of the RA patients in remission and healthy controls (P<0.05). The expression levels of CXCR3 mRNA were positively correlated with serum levels of ESR and CRP in clinical active RA group (r=0.824, r=0.765, P<0.05). In addition, RF titer, APF, AKA, and anti-CCP had no significant correlation with the expression levels of CXCR3 mRNA in RA patients (P>0.05). Conclusion RFQ-PCR is a sensitive,reproducible and practical test. The mRNA expressions of CXCR3 are significantly elevated in RA patients,which suggest that CXCR3 may be involved in the pathogenesis of RA. The mRNA expressions of CXCR3 in active RA patients are higher than those of RA patients in remission. These results indicate that CXCR3 may play an important role in the pathogenesis and progression of RA, and CXCR3 may be considered as an indicator for disease activity, therapeutic efficacy and prognosis of RA.

Objective To establish and apply the protein chip to detect eleven autoantibodies profile, and evaluate the authenticity and reliability with ANAs protein chip in clinical autoantibodies profile detection.Methods By comparing the results of IIF and ELISA , validation the sensitivity and specificity of ANAs protein chip in clinical autoantibodies profile detection. The autoantibodies detected were anti-SSA-52,anti-SSA-60,anti-SSB,anti-Sm,anti-RNP,anti-Scl-70,anti-Jo-1,anti-dsDNA,anti-rRNP,anti-centromere antibodies and antinuclear antibodies (ANA). To each autoantibody, we have selected 70 positive and 294 negative samples except the 32 rare samples that contain anti-Jo-1 antibody.Results The sensitivity to all the autoantibodies was 100% except anti-SSA52 and anti-SSB antibodies was 95.7%and 98.6% respectively. The specificity to all the autoanbodies was 100% except anti-SSB, anti-RNP-68, anti-Scl-70, anti-dsDNA, anti-CENP-B and ANA was 98.0%, 98.0%, 99.7%, 99.7%, 99.7% and 98.3% respectively. Conclusions To all the eleven antinuclear autoantibodies , the sensitivity is all above 95.0% and specificity is all above 98.0%, which indicate that there is high concordances between the ANAs protein chip and the methods used in clinical screening and confirmation,and it could meet the requirement of clinical autoantibodies profile detection. The protein chip method is fast, easy for detection with the characteristic of high-throughput,high sensitivity and specificity,it is hence recommended to apply ANAs protein chip to detect autoantibodies profile in clinical detection.

Objective To clone human Sjogren's syndrome antigen A(SSA)for expressing of antigen SSA-52kD and establishing a new clinical detecting method.Methods According to the human SSA-52kD cDNA sequence reported in GenBank,primers of human SSA-52kD cDNA were designed and synthesized.Human SSA-52kD cDNA was amplified from RNA of cultured Hela cell by reverse transcriptase polymerase chain reaction(RT-PCR).The production of amplification was ligated to PET-30a vector and then transformed into the competent bacteria DH5?to construct the recombinant plasmid PET-30a-SSA-52kD.The recombinant plasmid was digested with Bgl Ⅱ and Hind Ⅲ,and positive clones were sequenced.Results The Human SSA-52kD cDNA fragment containing 1447bp was amplified by RT-PCR.Restriction endonuclease mapping using Bgl II and Hind III showed that the target gene was inserted into the recombinant plasmid.The complete coding sequence of Human SSA-52kD was consistent with that of GenBank through DNA sequencing.Conclusions The full length of human SSA-52kD cDNA was successfully cloned and the recombinant plasmid PET-30a-SSA-52kD was constructed.

With the development of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors,the second generation of combined immunosuppressive agents emerge as the times require.As a bifunctional anti-PD-L1/transforming growth factor-β (TGF-β) fusion protein,M7824 can antagonize PD-L1 pathway and trap TGF-β at the same time,which can effectively enhance the immune response and reduce the occurrence of immune escape and drug resistance.The drug has achieved remarkable results in many preclinical studies,however,the indications,safety and efficacy still need to be confirmed by large-scale clinical research data.