Tapering of recombinant human tumor necrosis factor receptor-Fc fusion protein dosage combined with DMARDs in the treatment of peripheral joints involvement of ankylosing spondylitis / 中华风湿病学杂志

Objective To evaluate the clinical efficacy and safety of tapering the dosage of recom-binant human tumor necrosis factor receptor-Fc fusion protein (rhTNFR-Fc) combined with DMARDs in the treatment of peripheral joints involvement of ankylosing spondylitis. Methods Sixty patients who met the classification criteria of ankyloding spondylitis were enrolled. Meanwhile, all patients had one or more of the following joint involvement: hip, knee, ankle, and shoulder. Their BASDAI was higher than 4, joint pain VAS≥4, ESR ≥30 mm/1 h and CRP≥8 mg/L. Tuberculosis, hepatitis B, hepatitis C infection or other microorgan-isms infections were excluded. All enrolled patients had no serious heart,liver,kidney, or other internal organ involvement. During the first stage (The first eight weeks patients were matched by age and, disease activity, then randomly divided into the rhTNFR-Fc (the control group) treatment group in which patients were treated with 25 mg rhTNFR-Fc subcutaneous injection twice per week for 4 months) and rhTNFR-Fc dosage tapering group in which 25 mg rhTNFR-Fc were subcutaneously injected once per week for 4 weeks and then followed by 12.5 mg per week for 4 weeks, then once every 10 days for 6 times. Then the dosage of rhTNFR-Fc dosage of the dosage tapering group (the experimental group) was changed to 12.5 mg subcutaneous injection once every 15 days for another 4 times combined with methotrexate 7.5 mg per week and Salfasalazine 2 g daily and thalidomide 100 mg per night. The second stage started from week 9 to 24. In addition to the 30 cases at the first stage, 42 cases were included based on the same inclusion criteria for stage one. Patients' clinical and laboratory parameters were evaluated at week 0, 4, 8, 16 and 24. Results During the first four weeks, all patients of both control group and experimental group reached ASAS20, 97% (29/30) patients reached ASAS50 in the control group, 83% (25/30) patients reached ASAS50 in the experimental group. At week 8, patients in both groups maintained at 100% ASAS20 improvement, 100% (13/13) patients in the control group reached ASAS50, and that of the experimental group was 97% (29/30), the differences between the two groups were not statistically significant (P>0.05). In the second stage, 72 cases (100%) could achieve ASAS20, 63 cases (88%) achieved ASASSO at week 16. At week 24, 72 cases (100%) remained to achieve ASAS20, 71 cases (99%) achieved ASAS50. The safety and compliance of the two groups were good. Two cases developed infection, one patient had mild elevation of serum transaminase. Conclusion Tapering the dosage combined with DMARDs is an effective and safe approach in the treatment of peripheral joints involvement of ankylosing spondylitis. The compliance of this strategy is good and only few patients have serum transaminase elevation. But attention should be paid to the increased rate of infection.

Study on the gene polymorphism of TNF-α-238 in Ankylosing Spondylitis(AS)patients in Hunan population / 中国免疫学杂志

Objective:To explore the correlations of TNF-α-238 site gene polymorphism and the onset of Ankylosing Spondylitis(AS)in Hunan Han population.Methods:100 AS samples (including serum and whole blood) were collected from the Department of Immunology and Rheumatology of the Second Xiangya hospital from May 2008 to Jan 2009 and 90 samples of normal people were collected as control group.We detected the TNF-α-238 gene polymorphism of these subjects by using PCR-RFLP technique.The TNF-α level in the serum samples were measured by ELISA and HLA-B27 antigen was detected by flow cytometry (FCM).Then all of the data was analyzed by SPSS13.0 software.Results:There were 95 cases with the TNF-α-238 G/G genotype in 100 AS patients,5 cases with the G/A genotype.While in the control group,TNF-α-238 G/G genotype and G/A genotype were 88 cases and 2 cases respectively.There was no TNF-α-238 A/A genotype in both groups.The allele frequencies of G in AS group was higher than in the control group(98.9% vs.97.5%),while the allele frequencies of A in AS group was lower than in the control group(1.1% vs.2.5%).However,there were no significant difference both A allele frequencies and G allele frequencies (P＞0.05).In addition,the average TNF-α level in AS group was higher than in the control group significantly (10.16±1.19 pg/ml vs.5.64±1.18 pg/ml).And the average TNF-α level in AS patients with the genotype of G/A was higher than that of with the G/G genotype (13.49±1.27 pg/ml vs.9.44±1.29 pg/ml).There was a very large difference of the positive ratio of HLA-B27 between two groups (χ~2=114.975,P=0.000).After gene analysis of HLA-B27and TNF-α-238,the odds ratio(OR)was higher in both G/G genotype and HLA-B27 positive than HLA-B27 lonely.Conclusion:There is probably no relationship between the gene polymorphism of TNF-α-238 site and the onset of AS but the G/G genotype of TNF-α-238 may increase the sicken risk of AS in Hunan population.

Screening of specific serum biomarker of ankylosing spondylitis from a random peptide library / 中华检验医学杂志

short peptide AS1 screened from the phage random peptide library of 12 amino acids has antigenicity and can react with sera of AS patients. These findings indicate that AS1 could be one of candidate molecules of AS-specific serum markers.

The association analysis of plasma Hcy level and MTHFR gene polymorphism with ankylosing spondylitis / 中华风湿病学杂志

Objective To investigate the relationship between plasma homocysteine (Hey) level and ankylosing spondylitis (AS).To analyze the association between the NS,N10 methylenetetrahydrofolate reductase (MTFHR) gene polymorphism and AS.Methods One hundred patients with AS and 60 healthy controls were included in the study.The plasma Hey level was examined by enzyme-linked immunoadsorbent assay and MTHFR gene polymorphism was analyzed by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).Results Compared with heahhy controls,the plasma Hey level in AS patients was significantly higher than that of the controls (P＜0.01).There was no significant difference in the frequen-cies of MTHFR genotype and alleles between AS and the controls (P＞0.05),But the ratio of T/T genotype mutation was different between AS and the controls (P＜0.05).The plasma Hey level of T/T genotype was significantly higher than that of C/T or C/C genotype in AS and the controls (P＜0.01).Logisticalregression analysis indicated that Hey was an independent risk factor for AS (P＜0.01,0R=4.582,95%CI=1.984～10.585).Conclusion The plasma homocysteine level is significantly increased in AS patients.Hyperhomo-cysteinemia is an independent risk factor for AS.MTHFR T/T genotype mutation is an important mechanism of hyperhomocysteinemia and may be related with AS.