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1.
Chinese Medical Journal ; (24): 886-891, 2020.
Article in English | WPRIM | ID: wpr-827681

ABSTRACT

BACKGROUND@#Rheumatoid arthritis (RA), a systemic autoimmune disease characterized by synovial inflammation, can cause cartilage and bone damage as well as disability. The aim of this study was to explore whether serum glucose-6-phosphate isomerase (GPI) is correlated with disease activity and the value of GPI in the evaluation of infliximab treatment in patients with RA.@*METHODS@#Sixty-two patients with RA who had an inadequate response to methotrexate (MTX) were enrolled in Peking University People's Hospital from July 1, 2016 to July 31, 2018. Infliximab (3 mg/kg, intravenous at weeks 0, 2, and 6 and then every 8 weeks) was administered to patients with stable background MTX therapy. Serum samples were obtained at baseline and week 18. Serum GPI levels were determined using enzyme-linked immunosorbent assay. The associations between serum GPI levels and clinical features were analyzed.@*RESULTS@#Serum GPI was positively correlated with Disease Activity Score in 28 joints (DAS28), swollen joint count, tender joint count and C-reactive protein level (P < 0.001, P < 0.001, P < 0.001, and P = 0.033, respectively). The change of DAS28 in GPI-positive patients was greater than that in GPI-negative patients (P < 0.001). Compared with those for patients receiving MTX monotherapy at baseline, the GPI levels were significantly declined when MTX was combined with infliximab (P < 0.001).@*CONCLUSION@#Serum GPI is related to disease activity and clinical response to infliximab treatment.

2.
Chinese Medical Journal ; (24): 1397-1403, 2020.
Article in English | WPRIM | ID: wpr-827600

ABSTRACT

BACKGROUND@#Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort.@*METHODS@#Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis.@*RESULTS@#The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271-3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345-1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314-1.875, P = 0.013).@*CONCLUSION@#Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.

3.
Chinese Medical Journal ; (24): 1009-1014, 2019.
Article in English | WPRIM | ID: wpr-797469

ABSTRACT

Background:@#Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.@*Methods:@#This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.@*Results:@#In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ2=3.937, P=0.047), SDAI (χ2=4.666, P=0.031), and CliDR criteria (χ2=4.297, P=0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months, Z=-2.295, P=0.022).@*Conclusions:@#The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.

4.
Chinese Medical Journal ; (24): 2899-2904, 2019.
Article in English | WPRIM | ID: wpr-781747

ABSTRACT

BACKGROUND@#Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.@*METHODS@#We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.@*RESULTS@#A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001).@*CONCLUSION@#As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.

5.
Chinese Medical Journal ; (24): 1009-1014, 2019.
Article in English | WPRIM | ID: wpr-772185

ABSTRACT

BACKGROUND@#Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.@*METHODS@#This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.@*RESULTS@#In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ = 3.937, P = 0.047), SDAI (χ = 4.666, P = 0.031), and CliDR criteria (χ = 4.297, P = 0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8-72.3] months, Z = -2.295, P = 0.022).@*CONCLUSIONS@#The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.


Subject(s)
Adult , Aged , Antirheumatic Agents , Therapeutic Uses , Arthritis, Rheumatoid , Drug Therapy , Pathology , Cross-Sectional Studies , Female , Humans , Hydroxychloroquine , Therapeutic Uses , Leflunomide , Therapeutic Uses , Male , Methotrexate , Therapeutic Uses , Middle Aged , Retrospective Studies , Surveys and Questionnaires
6.
Chinese Medical Journal ; (24): 171-179, 2018.
Article in English | WPRIM | ID: wpr-342070

ABSTRACT

<p><b>BACKGROUND</b>Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients.</p><p><b>METHODS</b>Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender.</p><p><b>RESULTS</b>Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 ± 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 ± 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions.</p><p><b>CONCLUSION</b>IL1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.</p>

7.
Chinese Medical Journal ; (24): 1520-1526, 2018.
Article in English | WPRIM | ID: wpr-688082

ABSTRACT

<p><b>Background</b>Increased serum autoantibodies against interleukin-2 (anti-IL-2 autoantibodies) were reported in patients with systemic lupus erythematosus (SLE) and in patients receiving IL-2 therapy. This study aimed to explore the clinical relevance of serum anti-IL-2 autoantibodies and the interactions between low-dose IL-2 therapy and serum anti-IL-2 autoantibodies.</p><p><b>Methods</b>Serum samples were collected from 152 SLE patients and 100 age- and gender-matched healthy controls (HCs). Among them, 75 SLE patients were followed up for 10 weeks, and all of them were treated with corticosteroids, antimalarials, and/or immunosuppressants. Forty-six out of the 75 SLE patients received low-dose IL-2 therapy additionally. Clinical and laboratory parameters were collected at baseline and week 10. Serum anti-IL-2 autoantibodies were determined by enzyme-linked immunosorbent assay.</p><p><b>Results</b>Compared with HCs, median levels and positive rates of serum anti-IL-2 autoantibodies were higher in SLE patients (32.58 [23.63, 45.23] arbitrary unit [AU] vs. 37.54 [27.88, 60.74] AU, P = 0.006, and 5.0% vs. 18.4%, P = 0.002, respectively). Compared to those without the corresponding disorders, serum anti-IL-2 autoantibody was increased in patients with alopecia (49.79 [36.06, 64.95] AU vs. 35.06 [25.40, 58.46] AU, P = 0.033), but it was decreased in those with lupus nephritis (31.71 [22.60, 43.25] AU vs. 44.15 [31.43, 68.52] AU, P = 0.001). Moreover, serum anti-IL-2 autoantibody was positively correlated with serum IgA (r = 0.229, P = 0.005), total IgG (r = 0.327, P < 0.001), and total IgM (r = 0.164, P = 0.050). Treatment with exogenous IL-2 was not significantly associated with serum anti-IL-2 autoantibody. In addition, no significant difference was found in serum anti-IL-2 autoantibody between responders and nonresponders to low-dose IL-2 therapy.</p><p><b>Conclusions</b>Serum anti-IL-2 autoantibody was increased and associated with disease severity in SLE. Exogenous low-dose IL-2 did not significantly induce anti-IL-2 autoantibody production.</p>


Subject(s)
Adult , Autoantibodies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin-2 , Allergy and Immunology , Lupus Erythematosus, Systemic , Allergy and Immunology , Lupus Nephritis , Male , Middle Aged , Young Adult
8.
Chinese Medical Journal ; (24): 171-179, 2018.
Article in English | WPRIM | ID: wpr-771589

ABSTRACT

BACKGROUND@#Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients.@*METHODS@#Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender.@*RESULTS@#Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 ± 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 ± 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions.@*CONCLUSION@#IL1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.


Subject(s)
Adult , Aged , Arthritis, Rheumatoid , Genetics , Asians , Genetics , Case-Control Studies , China , Ethnology , Female , Genetic Predisposition to Disease , Genotype , Humans , Interleukin-1 , Genetics , Male , Middle Aged , Polymorphism, Single Nucleotide
9.
Chinese Medical Journal ; (24): 2683-2692, 2018.
Article in English | WPRIM | ID: wpr-775034

ABSTRACT

Background@#Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies.@*Methods@#ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout.@*Results@#ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population.@*Conclusions@#Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population.@*Clinical Trial Identifier@#NCT00856544 and NCT00413699.


Subject(s)
Administration, Oral , Adult , Aged , Arthritis, Rheumatoid , Drug Therapy , Asians , Female , Humans , Male , Middle Aged , Piperidines , Therapeutic Uses , Protein Kinase Inhibitors , Therapeutic Uses , Pyrimidines , Therapeutic Uses , Pyrroles , Therapeutic Uses , Surveys and Questionnaires , Young Adult
10.
Chinese Medical Journal ; (24): 1867-1871, 2013.
Article in English | WPRIM | ID: wpr-273080

ABSTRACT

<p><b>BACKGROUND</b>Acute gout is an intensely painful, inflammatory arthritis. Although the non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for this condition, the efficacy is based on only a few studies, particularly in China. We tried to assess the safety and efficacy of etoricoxib in the treatment of acute gouty arthritis in China.</p><p><b>METHODS</b>A randomized, double-blind, active comparator study was conducted at 10 sites in China. Patients (n = 178; ≥ 18 years of age) with acute gouty attack (< 48 hours) were treated for 5 days with etoricoxib (120 mg/d; n = 89) or indometacin (75 mg twice daily; n = 89). The primary efficacy end point was self-assessed pain in the affected joint (0-4 point Likert scale) from days 2 - 5. Secondary end points included investigator assessments of tenderness and swelling, patient/ investigator global assessments of response to therapy, and patients discontinuing treatment. Safety was assessed by adverse events (AEs).</p><p><b>RESULTS</b>Etoricoxib and indometacin had comparable primary and secondary end points. Mean change difference from baseline from days 2 - 5 was 0.03 (95% confidence interval (CI) -0.19 to 0.25; P = 0.6364), which fell within the prespecified comparative bounds of -0.5 to 0.5. No severe AEs were associated with etoricoxib use. Non-severe AEs were mainly digestive and general, and most (73.7%) were mild, although they caused withdrawal of two subjects in the etoricoxib group, due to bilateral renal calculi and uronephrosis of the left kidney (unrelated to etoricoxib) and fever and chills (potentially etoricoxib-related). Overall, AEs were similar, although the absolute number of AEs in the etoricoxib group (n = 31) was less than the indometacin group (n = 34).</p><p><b>CONCLUSIONS</b>Etoricoxib (120 mg once daily) is effective in treating acute gout, is generally safe and well-tolerated, and is comparable in efficacy to indometacin (75 mg twice daily).</p>


Subject(s)
Adult , Aged , Arthritis, Gouty , Drug Therapy , Cyclooxygenase Inhibitors , Therapeutic Uses , Double-Blind Method , Female , Humans , Indomethacin , Therapeutic Uses , Male , Middle Aged , Pyridines , Therapeutic Uses , Sulfones , Therapeutic Uses
11.
Chinese Medical Journal ; (24): 3115-3119, 2012.
Article in English | WPRIM | ID: wpr-316558

ABSTRACT

<p><b>BACKGROUND</b>Macrophage-inducible C-type lectin (MINCLE) is an important member of C-type lectin superfamily, which has been shown evidence for susceptibility to arthritis in animal models. We aimed to investigate the possible association of MINCLE with rheumatoid arthritis (RA) susceptibility in Chinese Han population.</p><p><b>METHODS</b>Haplotypes from HapMap database (Chinese Han Beijing, CHB) were used to select tag-single nucleotide polymorphism (SNP) (r(2) = 0.8) residing in MINCLE gene. A total of 563 patients with RA and 404 healthy controls were TagMan genotyped for SNP rs10841845. Association analyses were performed on the whole data set and on RA subsets based on gender difference and the status of anti-cyclic citrullinated peptide (anti-CCP) antibody in RA patients. Association statistics were calculated by age and sex adjusted logistic regression.</p><p><b>RESULTS</b>Overall, MINCLE SNP rs10841845 was not associated with susceptibility to RA. However, following anti-CCP stratification, rs10841845 GG genotypes conferred a significantly protective effects against anti-CCP-positive RA (OR 0.65, 95%CI 0.430 - 0.995, P = 0.048). Following gender stratification, SNP rs10841845 G allele appeared to insert its RA protective effect only in male patients, both at allele level (G vs. A OR 0.66, 95%CI 0.46 - 0.93, P = 0.018) and at genotype level (GG vs. AA+AG, OR 0.429, 95%CI 0.20 - 0.95, P = 0.036). Notably, the male RA protective effect of rs10841845 G allele was only seen in anti-CCP-positive RA (G vs. A: OR 0.64, 95%CI 0.43 - 0.96, P = 0.029; GG vs. AA+AG: OR 0.375, 95%CI 0.14 - 0.94, P = 0.038). Furthermore, we observed a significant reduction of Disease Activity Score (DAS) 28 score (3.91 ± 0.70 vs. 5.66 ± 0.31, P = 0.022) and serum C-reactive protein levels (31.64 ± 24.13 vs. 91.80 ± 12.02, P = 0.012) in male anti-CCP-positive RA patients carrying rs10841845 GG genotype, compared with patients carrying AA+AG genotypes.</p><p><b>CONCLUSIONS</b>Our study provides the evidence for a gender specific association between MINCLE rs10841845 and RA susceptibility. The SNP rs10841845 G allele appears to have protective effect against anti-CCP-positive RA and confer reduced RA activity in men.</p>


Subject(s)
Aged , Antibodies , Blood , Arthritis, Rheumatoid , Genetics , Allergy and Immunology , Female , Genetic Predisposition to Disease , Genotype , Humans , Lectins, C-Type , Genetics , Male , Middle Aged , Peptides, Cyclic , Allergy and Immunology , Polymorphism, Single Nucleotide , Receptors, Immunologic , Genetics
12.
Chinese Medical Journal ; (24): 2873-2877, 2012.
Article in English | WPRIM | ID: wpr-244333

ABSTRACT

<p><b>BACKGROUND</b>Toll like receptor (TLR) 9 has been shown to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) in animal models. Its pathogenic role in human SLE, however, was poorly elucidated. This study was performed to investigate the role of TLR9 involved in the aberrant signaling pathway and its correlation with disease activity in SLE.</p><p><b>METHODS</b>mRNA level of TLR9 and interferon (IFN) regulatory factor 5 (IRF5) in peripheral blood mononuclear cells (PBMCs) were determined by real-time polymerase chain reaction (PCR). IFN-a expression was measured in the serum of the SLE patients by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>TLR9 expression was significantly higher in SLE patients than that in health controls (P = 0.011). SLE patients with positive anti-dsDNA antibody had significantly higher expression of TLR9 than that with negative anti-dsDNA antibody (P = 0.001). TLR9 expression was positively correlated with fever (P = 0.017), alopecia (P = 0.046), safety of estrogens in lupus erythematosus national assessment SLE disease activity index (SELENA-SLEDAI) score (r(s) = 0.385, P = 0.003), and the level of IRF5 (r(s) = 0.35, P = 0.027) and IFN-a (r(s) = 0.627, P = 0.001) in SLE patients.</p><p><b>CONCLUSION</b>TLR9 is associated with SLE disease activity and might be involved in the IFN-a pathway of SLE.</p>


Subject(s)
Adolescent , Adult , Antibodies, Antinuclear , Blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interferon Regulatory Factors , Metabolism , Interferon-alpha , Blood , Leukocytes, Mononuclear , Metabolism , Lupus Erythematosus, Systemic , Blood , Genetics , Metabolism , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Toll-Like Receptor 9 , Genetics , Metabolism , Young Adult
13.
Chinese Medical Journal ; (24): 2477-2481, 2012.
Article in English | WPRIM | ID: wpr-283737

ABSTRACT

<p><b>BACKGROUND</b>Systemic lupus erythematosus (SLE) mostly occurred in young women. This study was undertaken to investigate the different clinical characteristics of SLE between male and female patients, and to identify the sex hormone levels and clinical outcomes of different gender in SLE patients.</p><p><b>METHODS</b>Of the 516 SLE patients admitted to the Peking University People's Hospital from January 2008 to December 2010, 58 were male and 458 were female. Clinical manifestations, laboratory profiles and disease activity scores were evaluated in male and female patients. Sex hormones levels were also compared among male patients.</p><p><b>RESULTS</b>The median age at SLE onset in male and female patients was 27.2 and 28.6 years, respectively. Compared with female patients, at onset of SLE, male patients showed higher rates of serious renal disease (58.6% vs. 47.2%, P = 0.064), neuropsychiatric SLE (20.7% vs. 12.0%, P = 0.055), and a higher incidence of anti-ds-DNA (25.9% vs. 16.8%, P = 0.069), anti-Sm (17.2% vs. 8.7%, P = 0.002), anti-Ro (46.6% vs. 28.4%, P = 0.004), anti-U1RNP (29.3% vs. 15.3%, P = 0.010), anticardiolipin antibody (25.9% vs. 11.4%, P = 0.004), and decreased C3 levels (67.2% vs. 49.8%, P = 0.009). Systemic lupus erythematosus disease activity index (SLEDAI) scores were higher in men than in women (16.8 vs. 12.8, P = 0.038). Of the 58 male patients, 24 had not received aggressive treatment during the three months prior to the study. Levels of testosterone and dihydroepiandrosterone (DHEA) were lower in male SLE patients than in male healthy controls (P = 0.004 and P = 0.006, respectively). Low serum testosterone was an independent risk factor for the development of lupus nephritis (P = 0.043). Male patients with elevated serum prolactin were at increased risk of developing neuropsychiatric manifestations of SLE (P = 0.081).</p><p><b>CONCLUSION</b>Early recognition of risk factors and appropriate intervention are essential, which might lead to high disease activity and serious systemic damage in male SLE patients.</p>


Subject(s)
Adult , Female , Humans , Lupus Erythematosus, Systemic , Pathology , Male , Retrospective Studies , Risk Factors , Sex Factors
14.
Chinese Medical Journal ; (24): 2490-2495, 2011.
Article in English | WPRIM | ID: wpr-338521

ABSTRACT

<p><b>BACKGROUND</b>Antibodies against type 3 muscarinic acetylcholine receptor (M3R) are involved in the pathogenesis of Sjögren's syndrome (SS), but the clinical value of them in SS patients has been controversial. The aims of this study were to: (1) establish an improved enzyme-linked immunosorbent assay (ELISA) to detect IgA antibodies against M3R; (2) evaluate the value of IgA antibodies against the second extracellular loop of M3R205-220 (c2M3RP) in diagnosis of SS.</p><p><b>METHODS</b>To increase the ELISA sensitivity, c2M3RP was coupled to bovine serum albumin (BSA) by the glutaraldehyde method and a 96-well microplate was treated by ultraviolet rays before coated. Concentrations of anti-c2M3RP, anti-SSA, and anti-SSB were measured in the sera of 240 individuals: 91 patients with primary SS and 149 controls (16 secondary SS, 27 systemic lupus erythematosus, 40 rheumatoid arthritis and 66 healthy controls). Diagnostic properties of anti-c2M3RP were determined by receiver-operating characteristic curve analysis.</p><p><b>RESULTS</b>The prevalence of serum IgA anti-c2M3RP antibodies in patients with pSS (46%, 42/91) was significantly higher than that in patients with systemic lupus erythematosus (19%, 5/27), in rheumatoid arthritis (15%, 6/40) and in healthy controls (5%, 3/66). However, there was no significant difference between the two SS groups (P = 0.727). The diagnostic performance of IgA anti-M3RP antibodies was similar to anti-SSA assay, but had 22% higher sensitivity than anti-SSB. By analyzing of IgA anti-c2M3RP antibodies, combination of anti-SSA and anti-SSB resulted in increased sensitivity, whereas their specificity was not significantly changed.</p><p><b>CONCLUSIONS</b>The improved anti-c2M3RP ELISA is a novel, sensitive, and specific serological test for the diagnosis of SS. The combined application of anti-c2M3RP, anti-SSA and anti-SSB tests can improve the laboratory diagnosis of SS. The IgA anti-c2M3RP antibodies may serve as a novel diagnostic marker for SS.</p>


Subject(s)
Adult , Aged , Aged, 80 and over , Animals , Autoantibodies , Allergy and Immunology , Biomarkers , Blood , Cattle , Enzyme-Linked Immunosorbent Assay , Methods , Female , Humans , Immunoglobulin A , Blood , Male , Middle Aged , Receptors, Muscarinic , Allergy and Immunology , Sjogren's Syndrome , Blood , Young Adult
15.
Chinese Medical Journal ; (24): 2863-2867, 2011.
Article in English | WPRIM | ID: wpr-292788

ABSTRACT

<p><b>BACKGROUND</b>A previous study has shown that rs548234 polymorphism at PRDM1-ATG5 region is associated with rheumatoid arthritis (RA) in Caucasian populations. The aim of this study was to investigate the effect of rs548234 polymorphism at PRDM1-ATG5 region on susceptibility to RA in Chinese Han population.</p><p><b>METHODS</b>We genotyped 848 RA patients and 1431 matched healthy controls for rs548234 single-nucleotide polymorphism (SNP) with a predesigned TaqMan SNP genotyping assay. Association analyses were performed on the whole data set and on rheumatoid factors (RF) and anti-cyclic citrullinated peptides (anti-CCP) antibody. Finally, we carried out combined analysis of rs548234 association with RA based on the published data.</p><p><b>RESULTS</b>No significant difference in the genotype distribution between RA patients and healthy controls for rs548234 (C/T) polymorphism was found in Chinese Han population, neither in whole data set nor in stratified subsets, e.g. RF and anti-CCP status. Association analysis in different ethnic groups showed that rs548234 at PRDM1-ATG5 region was associated with RA in Caucasian ancestry but not in East Asian population.</p><p><b>CONCLUSIONS</b>Our results showed no involvement of rs548234 at PRDM1-ATG5 region in the susceptibility or clinical relevance of RA in Chinese Han population.</p>


Subject(s)
Adult , Aged , Arthritis, Rheumatoid , Epidemiology , Genetics , Asians , Autophagy-Related Protein 5 , Female , Genetic Predisposition to Disease , Genetics , Genotype , Humans , Male , Microtubule-Associated Proteins , Genetics , Middle Aged , Polymorphism, Single Nucleotide , Genetics , Positive Regulatory Domain I-Binding Factor 1 , Repressor Proteins , Genetics
16.
Chinese Medical Journal ; (24): 1407-1412, 2010.
Article in English | WPRIM | ID: wpr-241770

ABSTRACT

<p><b>BACKGROUND</b>Rheumatoid arthritis (RA) is characterized by inflammation of the synovial membrane, leading to invasion of synovial tissue into the adjacent cartilage matrix with degradation of articular cartilage and bone as a consequence. Dickkopf-1 (DKK-1) and osteoprotegerin (OPG) have been demonstrated to be key molecules involved in bone erosion and bone remodeling. The aim of this study was to explore the potential role of DKK-1 and OPG in different stage of RA.</p><p><b>METHODS</b>The protein levels of DKK-1 and OPG were detected by ELISA. The serum samples were collected from 300 patients with RA and 60 healthy controls. Of which, 150 RA patients were defined as early RA (disease duration < or = 1 year), and other 150 RA patients were defined as longlasting RA (disease duration > or = 5 years). At the time of serum sampling, various clinical and laboratory parameters were assessed. The correlations of DKK-1 or OPG and clinical/laboratory parameters were analyzed.</p><p><b>RESULTS</b>The serum level of DKK-1 was elevated in patients with longstanding RA compared with healthy controls, while no significant difference was observed between the two groups in the level of OPG. In contrast, in early RA patients, the circulating OPG was elevated, while there was no significant difference between the two groups in expression of DKK-1. The serum DKK-1 was correlated with Sharp score and DAS28 in longstanding RA patients. In early RA, age was the only parameter that was significantly related to serum OPG.</p><p><b>CONCLUSIONS</b>There was a cross-talk between DKK-1 and OPG, which involved in bone destruction in RA. In different stage of RA, DKK-1 and OPG may play different roles in the pathogenesis of RA.</p>


Subject(s)
Adult , Arthritis, Rheumatoid , Blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Intercellular Signaling Peptides and Proteins , Blood , Male , Middle Aged , Osteoprotegerin , Blood , Time Factors
17.
Chinese Medical Journal ; (24): 3173-3177, 2010.
Article in English | WPRIM | ID: wpr-241611

ABSTRACT

<p><b>BACKGROUND</b>Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations. In order to examine whether the allele distribution of the single nucleotide polymorphism (SNP) in gene STAT4 rs7574865 in patients with SLE is different from those of healthy controls in Chinese Northern Han population, we investigated whether the variants of STAT4 rs7574865 were associated with any specific clinical features of SLE.</p><p><b>METHODS</b>We genotyped SNPs in STAT4 rs7574865 in 252 patients with SLE and 497 healthy controls. All subjects were from the Northern part of Chinese Han population. The genotypes in rs7574865 were determined by polymerase chain reaction (PCR) and consequence direct sequencing of PCR products in the DNA samples.</p><p><b>RESULTS</b>There was a significant difference in distribution of the SNPs in rs7574865 between the SLE patients and healthy controls. Compared with healthy controls, there was a significant correlation between TT genotypes in rs7574865 and the risk of SLE when GG genotype was used as a reference genotype after adjusting for gender and age. The frequency of T allele in the SLE patients was strongly significantly higher than that of healthy controls. Furthermore, there was a significant difference in the distribution of SNP in rs7574865 between male and female SLE patients, when compared with healthy controls. The frequency of T allele in rs7574865 in male patients was significantly higher than that of male healthy controls or female patients. There was no significant correlation between the frequencies of T allele in STAT4 rs7574865 and the clinical features of SLE.</p><p><b>CONCLUSIONS</b>The SNP rs7574865 in STAT4 is strongly associated with risk of SLE in the Chinese Northern Han population. The TT genotype and T allele in STAT4 rs7574869 are susceptibility factors for SLE, especially for male SLE patients.</p>


Subject(s)
Adult , Asians , Genetics , Female , Genetic Predisposition to Disease , Genetics , Genotype , Humans , Linkage Disequilibrium , Genetics , Lupus Erythematosus, Systemic , Genetics , Male , Middle Aged , Polymorphism, Single Nucleotide , Genetics , STAT4 Transcription Factor , Genetics , Young Adult
18.
Article in English | WPRIM | ID: wpr-243614

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA).</p><p><b>METHODS</b>A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen for this 17-week, randomized, double-dummy, diclofenac sodium-controlled trial, with diacerein dosage of 100 mg/d and diclofenac sodium of 75mg/d. Efficacy and safety of both drugs were evaluated.</p><p><b>RESULTS</b>Totally 106 patients in the diacerein group and 107 patients in the diclofenac group were considered qualified for the evaluation. After 12 weeks of treatment, the total effective rates of patients/physicians' overall assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2%, respectively (P > 0.05). The primary efficacy parameter [visual analog scale (VAS) assessment of pain on 20 metres walking] and the secondary efficacy parameters [tenderness on palpation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short-Form (SF-36) Health Survey] significantly improved compared with baseline in both groups (P < 0.05). In the follow-up period, there were no obvious changes in above parameters in diacerein group. However, in diclofenac group, pain on 20 metres walking, tenderness on palpation, and WOMAC became aggravated after withdrawing the drug for 4 weeks (P < 0.05). Moreover, the consumption of paracetamol was significantly lower in diacerein group than in diclofenac group during follow-up (P < 0. 001). The incidences of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group, respectively. Mild-to-moderate gastrointestinal disorders were the most frequent adverse events.</p><p><b>CONCLUSIONS</b>Diacerein is as effective as diclofenac sodium in treating patients with knee OA. Furthermore, it has better extended effect and a good safety profile. It is generally well tolerated and has no severe adverse effect.</p>


Subject(s)
Adult , Aged , Anthraquinones , Therapeutic Uses , Anti-Inflammatory Agents, Non-Steroidal , Therapeutic Uses , Diclofenac , Therapeutic Uses , Double-Blind Method , Female , Humans , Male , Middle Aged , Osteoarthritis, Knee , Drug Therapy , Safety
19.
Article in Chinese | WPRIM | ID: wpr-683290

ABSTRACT

Objective To study clinical significance of anti-momoner C-reactive protein (anti- mCRP) antibody in systemic lupus erythematosus (SLE) and assess the relationship between serum CRP and anti-mCRP antibody.Methods Enzyme-linked immunosorbent assay (ELISA) was applied to determine serum level of anti-mCRP antibody in 113 pateints with SLE,65 patients with other rheumatic diseases,including primary Sjgren syndrome,rheumatoid arthritis,osteoarthritis,ankylosing spondylitis and systemic sclerosis,and 32 healthy controls.Serum level of CRP was evaluated by turbidimetry.Clinical manifestations and laboratory indicators of the patients were all recorded.Results Serum level of anti- mCRP antibody in SLE patients was significantly higher than that in patients with other rheumatic diseases and healthy controls,respectively (t=2.502 and 5.352,respectively,P 0.05).Titer of anti-mCRP antibody closely correlated with systemic lupus erythematosus disease activity index score (r=0.248,P0.05). Conclusions Level of Anti-mCRP antibody increased significantly in patients with SLE,which associated with disease activity of SLE and can be used as a valuable marker in evaluating activity of SLE.

20.
Article in Chinese | WPRIM | ID: wpr-685148

ABSTRACT

Objective To investigate the effects of anti-cell membrane associated DNA (mDNA) antibodies in the diagnosis of systemic lupus erythematosus (SLE) lacking of specific autoantibodies including anti Sm,anti ds-DNA,and anti-nucleosome antibodies.Methods Indirect immunofluorescence assay was used to measure anti-mDNA antibodies in serum of 145 SLE patients,and indirect immunofluorescence,Western-blot and ELISA were used to detect the anti-dsDNA ,anti-Sm and anti- nueleosome antibodies respectively to analysis the value of anti-mDNA antibodies on the specific autoantibodies negative patients with SLE.Results The sensitivity for anti-mDNA antibodies (69.7%) in SLE was significantly higher than anti-Sm (19.7%),anti-dsDNA ( 31.9% ) and anti-nucleosome (45.8% ).The incidences of anti-mDNA antibodies in SLE lacking of anti-dsDNA,Sm and anti-nueleosome antibodies (AnuA) were 64.3% ,70.2% and 60.3% respectively.Conclusion Anti-mDNA antibodies are serologic marker of SLE and important in diagnosis of SLE lacking of anti-dsDNA,Sm and nucleosome antibodies.

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