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Objective To validate the discriminatory capacity of the new ankylosing spondylitis disease activity scores (ASDAS) in Chinese ankylosing spondylitis (AS) patients, and assess its clinical value. Method One hundred and twenty-nine patients with AS was included in the study, in which 87 were par-ticipat clinical trials with Etanercept (n=87) and 42 were participants of clinical trails with. The disease activity and treatment effecticacy were assessed by ASDAS, BASDAI and patient global assessment. Discriminatory ability of all the measures was analyzed as standardized mean difference (SMD) and (-score. Pearson's correlation, two indepen -dent samples t test and simple linear regression model were used for statistical analysis. Result The four ASDAS scores correlated well with patient global assessment (r=0.56～0.74), ESR (r=0.50～0.80) and CRP (r=0.50～0.69) both at baseline and the changes form baseline to 6 weeks after treatment. The four ASDAS outperformed BASDAI, patient global assessment, ESR and CRP in differentiating patients with different levels of disease activity and patients with different levels of change. There was little difference in performance between the four ASDAS versions. Conclusion The four ASDAS are highly discriminatory in evaluating the disease activity and the efficacy of drugs in Chinese AS patients, showing a significant value in clinical practice.
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Objective To evaluate the efficacy and safety profile of a recombinant human tumor necrosis factor receptor: Fc fusion protein in ankylosing spondylitis (AS). Methods This was a multicenter,randomized, double-blind, placebo-controlled trial in the first 6 weeks and then followed by an open-labeled trial in the next 6 weeks. One hundred and forty-three patients of active AS were randomly assigned to receive 25 mg twice-weekly subcutaneous injections of rhTNFR:Fc or placebo for 6 weeks. The primary endpoint was proportion of ASAS20 responders at week 6. The secondary endpoints were the proportion of subjects achieving a BASDAI 20%, BASDAI 50% and BASDAI 70% improvement at week 6. Other secondary endpoints, related to reducing signs and symptoms of AS and improving range of motion and physical function, were evaluated.Results Treatment with rhTNFR:Fc resulted in significant improvement. At 6 weeks, 68% of the 71 patients in the rhTNFR: Fc group had a treatment response, as compared with 28% of those in the placebo group(P＜0.01). Improvements over base-line values for other measures of disease activity were significantly greater in the rhTNFR:Fc group, rhTNFR:Fc was well tolerated, The most frequently treatment related adverse event was injection site reaction. Conclusion rhTNFR:Fc has demonstrated consistent evidence of efficacy and is well tolerated in the treatment of active AS.
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Objective To investigate the distribution of HLA-B27 subtypes in ankylosing spondylitis(AS) patients of Chinese Han population by using the updated HLA-B27 typing data. Methods One hundred AS subjects were randomly selected from spondyloarthritis patients data bank of the third affiliated hospital of Sun Yat-sen university. All subjects were independent individuals, and the duplicated samples in the same family were excluded. Salt fraction method was used to prepare genome DNA. Luminex liquid array combining PCR-SSOP was used to perform the low resolution HLA-B genotyping. PCR-SSP was applied to perform the high resolution HLA-B27 typing for HLA-B27 positive subjects. Results Ninety-eight independent AS patients were recruited randomily, of which, 93 were HLA-B27 positive, with positive rate 94.9%, and covered 96% patients with family history of AS. Three subtypes were detected in this population including B * 2704 (n=76, 81.7%), B * 2705 (n=12, 12.9%) and B * 2715 (n=5, 5.4%). Compared with the two reports about HLA-B27 subtype distribution in healthy HLA-B27 positive Han population there was no significant difference between AS patients and healthy controls. But no B * 2715 case was found in those two reports of healthy population. Three reports (including 1 report in Chinese) could found about B * 2715 subtype, but all positive cases were oriental people. Furthermore, all B * 2715 positive patients were AS patients. Conclusion B * 2704 is the predominant subtype ,in AS patients of Chinese Han population, and followed by B * 2705. We found five cases with positive B * 2715, a considerable rare allele. This may suggest association between B * 2715 and AS.
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Objective To investigate the reasons for delayed diagnosis of ankylosing spondylitis(AS) in a Chinese population.Methods Three hundred and eight patients fulfilled the 1984 Modified New York criteria of AS were enrolled.They were interviewed in person or by telephone by rheumatologists for 13 ques-tions.Results Of the 308 AS patients.238(75%)completed 13 questions.Among these 238 patients,male to female ratio was 6 to 1.The average age at AS onset was 22.1 years.Those aged under 15 years at disease onset Was 18.1%.and between 15 and 39 years was 79.0%while over 39 years was 2.9%.Of these 238 pa-tients.27(23.9%)had family history of AS.84.9% of the patients were HLA-B27 positive.The average dura-tion of delayed diagnosis in HLA-B27(+)and HLA-B27(-)were 70.1 and 88.1 months respectively,which was not significant statistically.Among those delayed over 10 vears,24 AS patients were HLA-B27(+)and 10 were HLA-B27(-),which was statistically significant(P=0.012).66.4% of 238 patients were misdiagnosed, of which 23.4%were diagnosed as arthritis associated with rheumatic fever,22.9% as fatigue and 20.3%as inter-vertebrate disc.45.0%were misdiagnosed by one physician while 2 1.4%were misdiagnosed for several times,and the average length of delay diagnosis was 72±68 months.Seven cases,although the diagnosisi was being delaved for more than 10 years the initial diagnosis was correct. Conclusion Delayed diagnosis of AS is common in China.The major reasons for delayed diagnosis are HLA-B27 negative and lack of X-ray changes of sacroiliac joint at the initial visit.
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Objective To search for the genetic and molecular immunity basis of CXCR-1 associated pathogenesis in ankylosing spondylitis (AS) patients. Methods Sequencing analysis was used to detect mutation in the exonic, junctional and promoter sequences of CXCR-1 which might be related with ankylosing spondylitis; the hydrophobicity, conservation and evolutionary distance of the mutated amino acids were also analyzed. Results Six affected individuals in the family were detected with a novel mutation Arg192Gly. The glycine at 192 codon was highly conserved in different species. Arginine and glycine had quite distinct hydrophobicity and BLOSUM score. Conclusion The mutation CXCR-1 (Arg192Gly) detected in these patients might be involved in genetic and molecular immunity mechnisms of ankylosing spondylitis.
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Objective To study the single nucleotide polymorphisms (SNPs) in IL-23R gene in Chinese Han population with ankylosing spondylitis (AS). Methods SNPs rs11209026, rs1343151, rs11209032 and another three SNPs near them based on their physical distances were genotyped by PCR-directed sequencing. Hardy-Weinberg equilibrium, genotypes and allele frequency analysis were analyzed by SPSS 13.0. Linkage disequilibrium and haplotype analysis were carried out by SHEsis software. Results The difference of genotypes of rs11209032 and the difference of genotypes and allele frequencies of rs6677188 between patients and controls were statistically significant (P＜O.01) ; The two SNPs rs11209032 and rs6677188 had strong linkage disequlibfium (D'=0.925, r2=0.561 ). Haplotype analysis had shown a higher proportion of GAC haplotype in patients and a higher proportion of GTC haplotype in controls. Conclusion These results suggest that IL-23R polymorphisms is associated with susceptibility to AS in Chinese Han population and IL-23R gene may be a susceptible gene of AS.
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BACKGROUND: Human leukocyte antigen (HLA)-B27 is closely connected to the occurrence of some rheumatic diseases such as ankylosing spondylitis and can be used as an important factor for evaluating the diagnosis of ankylosing spondylitis. Immunomagnetic separation and enzymelinked immunosorbent assay (IMS-ELISA) has been applied to the detection of HLA-B27.OBJECTIVE: To explore the accuracy, sensitivity and specificity of IMSELISA for detecting HLA-B27 and its value in the auxiliary diagnosis of ankylosing spondylitis.DESIGN: A clinical trial in comparison with the gold standard.SETTING: Departments of Rheumatology and Clinical Laboratory, Third Affiliated Hospital of Sun Yat-sen University.PARTICIPANTS: Eighty-six patients suffering from low back pain and/or arthritis who were treated for the first time in Department of Rheumatology from December 2002 to April 2003. Inclusion criteria: ① Presence of manifestations of low back pain and/or arthritis; ② Thorough documentation of clinical and other examinations; ③ Informed consent to HLA-B27 examination; ④ Treatment for the first time in the Third Affiliated Hospital of Sun Yet-sen University. Those with other serious diseases or with incomplete record of clinical and/or accessory examinations were excluded. The 86 patients included 56 male and 30 female patients aged from 12 to 65 years.METHODS: Blood sample was detected for HLA-B27 by both IMS-ELISA and microlymphocytotoxicity test, and the latter was selected as the gold standard. The coincidence rate of the results detected by the two methods as well as the sensitivity, specificity, positive and negative predictive values of IMS-ELISA were calculated.MAIN OUTCOME MEASURES: ① The coincidence rate of the results of the two methods. ② The sensitivity and specificity of IMS-ELISA for detecting HLA-B27.RESULTS: None of the patients was lost. For the 33 patients with ankylosing spondylitis, the positivity rate of IMS-ELISA (90.9％) was higher than that of microlymphocytotoxicity test (87.9％), but the difference was not statistically significant (P＞0.05). The total coincidence rate of the two methods was 93.0％ in all the 86 patients. The sensitivity, specificity, positive and negative predictive values of IMS-ELISA were 90.0％, 95.7％,94.7％ and 91.7％ respectively.CONCLUSION: Both IMS-ELISA and microlymphocytotoxicity test are capable of reliable examination of HLA-B27 with high sensitivity and specificity.