Qiujing Wei

Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis

The objective of this study was to investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in ankylosing spondylitis (AS) patients. IL-23 and IL-17 levels in the serum and supernatants of cultured peripheral blood mononuclear cells (PBMCs) were determined by ELISA. IL-23p19 mRNA expression in PBMCs were analyzed using RT-PCR. The patients with AS at active stage showed elevated levels of IL-23 and IL-17 in the serum and supernatants of cultured PBMCs. A higher expression of IL-23p19 mRNA in PBMCs of AS patients was also observed. A significantly enhanced production of IL-17 in the supernatants of cultured PBMCs was found in the presence of recombinant IL-23 and this effect was more significant in patients with AS. The results suggest that IL-23 and IL-17 may play critical roles in the pathogenesis of AS and IL-23-stimulated production of IL-17 by PBMCs may be responsible for the development of AS.

An epidemiological survey of low back pain and axial spondyloarthritis in a Chinese Han population

Objective: To investigate the prevalence of low back pain (LBP) and axial spondyloarthritis (SpA) in a Chinese Han population. Methods: A face-to-face investigation was performed in the Han population of Dalang Town, Yangshan County, Guangdong Province, China, using a questionnaire established in France in 1999. First the clinical features associated with SpA were investigated, then the human leucocyte antigen (HLA)-B27 and sacroiliac joint radiographic examinations were carried out. Finally, the diagnosis of SpA was determined by rheumatologists. Results: A total of 13 315 subjects participated in the study and 10 921 were aged >16 years; of these, 787 (7.21%) had LBP. There were 92 axial SpA patients (0.782% in subjects >16 years old and 11.96% in subjects with LBP). There were 29 (0.253%) cases of ankylosing spondylitis (AS), 60 (0.507%) undifferentiated axial SpA (USpA), and three (0.022%) psoriatic arthritis (PsA). Patients in the SpA groups had higher percentages in onset <40 years, insidious onset, morning stiffness, and affected for >3 months compared with those in other LBP groups. Simultaneous symptoms associated with spondylitis, such as buttock pain, heel pain, psoriasis, and SpA family history, were more commonly present. Of the axial SpA patients, 82.67% were HLA-B27 positive, clearly a greater percentage than those (11.65%) in other LBP groups. Conclusions: The survey questionnaire for SpA in this study is useful for axial SpA screening in China. In southern China, the prevalence of LBP is 7.21%. The prevalence of axial SpA is 0.782%. USpA is the most common subtype of SpA, followed by AS.

MiR-27a Targets sFRP1 in hFOB Cells to Regulate Proliferation, Apoptosis and Differentiation

MicroRNAs (miRNAs) play a key role in the regulation of almost all the physiological and pathological processes, including bone metabolism. Recent studies have suggested that miR-27 might play a key role in osteoblast differentiation and bone formation. Increasing evidence indicates that the canonical Wnt signaling pathway contributes to different stages of bone formation. In this study, we identify miR-27a can promote osteoblast differentiation by repressing a new target, secreted frizzled-related proteins 1 (sFRP1) expression at the transcriptional level. Here, 21 candidate targets of miR-27a involved in canonical Wnt/β-catenin signaling were predicted, and a significant decrease in sFRP1 luciferase activity was observed both in 293T and MG63 cells co-transfected with the matched luciferase reporter constructs and miR-27a mimic. Furthermore, the presence of exogenous miR-27a significantly decreased sFRP1 mRNA and protein expression in hFOB1.19 cells during both proliferation and osteogenic differentiation. The over-expression of miR-27a or knockdown sFRP1 significantly increased the percentage of apoptotic hFOBs, the percentage of cells in the G2-M phase of the cell cycle and the expression of key osteoblastic markers, including ALP, SPP1, RUNX2 and ALP activity. Over-expression of miR-27a or knockdown of endogenous sFRP1 led to an accumulation of β-catenin in hFOBs. In the present study, we demonstrate that miR-27a induced gene silencing effect is a vital mechanism contributing to bone metabolism in hFOB cells in vitro, which is partly affected by the post-transcriptional regulation of sFRP1, during osteoblast proliferation, apoptosis and differentiation.

Adalimumab significantly reduces inflammation and serum DKK‐1 level but increases fatty deposition in lumbar spine in active ankylosing spondylitis

To investigate whether adalimumab is effective for active ankylosing spondylitis (AS) patients and whether it has an impact on the formation of fatty deposition lesions (FDL) and serum Dickkopf homolog 1 (Dkk‐1) level in AS patients.

The Ankylosing Spondylitis Disease Activity Score is a highly discriminatory measure of disease activity and efficacy following tumour necrosis factor-α inhibitor therapies in ankylosing spondylitis and undifferentiated spondyloarthropathies in China

OBJECTIVE To validate the clinical value of the new Ankylosing Spondylitis Disease Activity Scores (ASDASs) in assessing the disease activity and efficacy of TNF-α inhibitor in AS and uSpA patients in China. METHODS Two hundred and thirty patients were included in our study. They consisted of patients with active AS (n = 87) and uSpA (n = 30) participating in a double-blind placebo-controlled randomized clinical trial of etanercept and patients with active AS (n = 58) and uSpA (n = 55) treated with infliximab. The disease activity and treatment effects were assessed by ASDAS, BASDAI, patient global and the acute inflammation score of lumbar and SI joints by MRI. Discriminatory ability of all the measures was analysed by standardized mean difference and t-score. RESULTS In both the AS and uSpA groups, ASDAS correlated well with patient global score (AS group: r = 0.65-0.72; uSpA group: r = 0.52-0.62), ESR (AS group: r = 0.57-0.81; uSpA group: r = 0.63-0.85) and CRP (AS group: r = 0.51-0.70; uSpA group: r = 0.61-0.76) both at baseline and in changes from baseline to 6 weeks after TNF-α inhibitor treatment. The ASDAS scores outperformed BASDAI, patient global score, ESR, CRP and the acute inflammation score by MRI in differentiating patients with different levels of disease activity and patients with different levels of change in both AS and uSpA groups. There was little difference in performance between the two versions of the ASDAS. CONCLUSION The new ASDAS is a highly effective measure in assessing disease activity and a great discriminatory measurement to assess the efficacy of TNF-α inhibitor in Chinese AS patients and uSpA patients.

HLA‐B27 polymorphism in patients with juvenile and adult‐onset ankylosing spondylitis in Southern China

Distribution of B27 subtypes in juvenile and adult-onset ankylosing spondylitis (JAS and AAS) in Southern China was studied. A total of 505 patients belonged to Han population were included (145 JAS and 360 AAS patients), and 1368 healthy individuals were included as controls. Human leukocyte antigen (HLA)-B27 typing was performed by Luminex liquid array combining polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) and/or serological method. HLA-B27 subtyping was performed by polymerase chain reaction-sequence specific primer (PCR-SSP). The sequence-based typing was performed for the B*2715 samples to verify the PCR-SSP results. HLA-B27 was presented in 453 of 505 patients (89.7%), compared with 74 of 1368 controls (5.41%). B*2704 subtype in AS group was significantly higher than controls and B*2705 subtype significantly lower. B*2715 and B*2702 were found in 1.32% and 0.66% of the B27-positive patients but none in controls, and there was no significant difference between either of them and controls. B27-positive patients were 134 (92.4%) in JAS group and 319 (88.6%) in AAS group. There was no significant difference for B27 subtypes distribution between JAS (B*2704, 05, 15) and AAS (B*2704, 05, 15, 02) groups. The frequency of B*2715 in two groups was 3 (2.24%) and 3 (0.94%), respectively. The onset age of three JAS patients carrying B*2715 was 5, 9 and 13 years old, respectively. Our results suggested that B*2704 was the predominant subtype in AS patients in Southern China. B*2715 was observed in AS group only and slightly more in JAS than in AAS, and the patients carrying this allele tended to have early onset, B*2715 may be disease-association subtype.

Association of IL-1 gene complex members with ankylosing spondylitis in Chinese Han population.

There are reports of IL‐1 complex gene polymorphisms in ankylosing spondylitis (AS; MIM 106300), but the results have been inconsistent among populations. Moreover, few studies examine the association between IL‐1 complex gene polymorphisms and clinical symptoms of AS patients. We investigated polymorphisms of IL‐1 complex with AS in the Chinese Han population in this study. Chinese Han AS patients and ethnically matched healthy controls were genotyped for five single nucleotide polymorphisms (IL1β+3953, β‐511, F10.3, RN.4, RN.6/1) and the IL1RN.VNTR of IL‐1 gene cluster. Allele, Genotype and haplotype frequencies were compared between cases and controls by SHEsis software. The frequency of allele C of the marker IL1F10.3 was significantly increased in AS patients versus controls [p = 0.001, odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.19–1.20; p = 0.002, respectively]. Strong linkage disequilibrium was identified between IL1B‐511, IL1B+3953 and RN4 in both patients and healthy controls (D′ > 0.95). Haplotypes of pairs of these markers (6) were also significantly associated with AS. The strongest associations observed was between allele combination B‐511‐T/B+3953‐C/F10.3‐C/RN4‐T/RN2VNTR‐1/RN6.1‐C and AS (p = 3.32 × 10−5, OR = 4.41, 95% CI=2.1–9.3). Clinical manifestation showed week association between RN2VNTR A2 allele and risk of peripheral arthritis (OR = 0.2, 95% CI = 0.07–0.91). The IL‐1 gene cluster is associated with AS in Chinese population. This finding provides strong statistical support for the previously observed relationship and indicates possible association between clinical manifestation and genetic factor.

Single-nucleotide polymorphisms and expression of IL23R in Chinese ankylosing spondylitis patients

The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) in IL23R with ankylosing spondylitis (AS) in Chinese Han population. Six SNPs were selected for analysis in AS patients and controls. The IL23R mRNA expression was detected using RT-PCR. The differences in the genotypes of rs11209032 and the differences in the genotypes and allele frequencies of rs6677188 between cases and controls were significant. The two SNPs rs11209032 and rs6677188 were in strong linkage disequilibrium. Haplotype analysis noted a higher proportion of GAC in cases and a higher proportion of GTC in controls. The patients with AS showed an elevated level of IL23R mRNA in PBMCs. This study suggested that IL23R polymorphisms were associated with susceptibility to AS in the Chinese population and that IL23R may be involved in the development of AS.

ERAP1 is associated with ankylosing spondylitis in Han Chinese.

Objective. Genetic components play important roles in the incidence and development of ankylosing spondylitis (AS). Aminopeptidase regulator of tumor necrosis factor receptor shedding 1 (ERAP1) was recently found to be associated with AS in North American and British cohorts. We evaluated whether ERAP1 is associated with AS in a Chinese Han population. Methods. A sample of 50 patients and 50 healthy controls was recruited for preliminary screening for informative single-nucleotide polymorphisms (SNP). Then 6 SNP of suggestive significance in the initial screening were followed up in a large sample of 471 patients with AS and 456 ethnically matched controls. Diagnosis of AS followed the 1984 modified New York criteria. Linkage disequilibrium coefficient (D’ and r2) and haplotypes were estimated by Haploview. Result. Two SNP (rs27434, p = 0.00039, and rs27529, p = 0.0083) in ERAP1 other than that reported previously were found to be significantly associated with AS. Haplotype analysis using 5 SNP within 1 linkage disequilibrium block identified 2 risk haplotypes (GATGT and GACGT) and 1 protective haplotype (GGTGT) for AS. Conclusion. Our study demonstrated that 2 novel SNP in ERAP1 were associated with AS in the Han Chinese population, suggesting that ERAP1 might confer genetic risk for AS in Han Chinese through the common mechanism shared by different populations, although the AS-associated SNP in ERAP1 might be population-specific.

Higher risk of uveitis and dactylitis and older age of onset among ankylosing spondylitis patients with HLA-B*2705 than patients with HLA-B*2704 in the Chinese population.

Human leukocyte antigen (HLA)-B27 is closely associated with ankylosing spondylitis (AS). However, the exact correlation between HLA-B27 subtypes and AS manifestations remains unknown. This study aimed to investigate the correlation between HLA-B27 polymorphism and the clinical features of AS. This study included 846 patients with AS and 959 healthy controls. Direct sequencing was used to identify the HLA-B27 genotype. Clinical parameters, including age, age of onset, family history, low back pain, peripheral arthritis, hip joint involvement, dactylitis, uveitis, and sex ratio, were compared among patients with various HLA-B27 subtypes. In total, 741 AS patients (87.6%) and 39 healthy controls (4%) were HLA-B27-positive. The most prevalent subtypes were HLA-B*2704 (88%) and HLA-B*2705 (10.1%) in patients with AS. Compared with HLA-B*2704-positive patients, HLA-B*2705-positive patients demonstrated a significant increase in the incidence of uveitis (16% vs 6.13%, P = 0.002) and dactylitis (9.3% vs 3.8%, P = 0.028) and they had an older age of onset (22.9 ± 8.0 vs 20.7 ± 6.7 years, P = 0.028). Binary logistic regression analysis revealed that presence of uveitis was significantly associated with HLA-B*2705 (P = 0.008; odds ratio, 2.63; 95% confidence interval, 1.283-5.393). There were no significant differences in family history, low back pain, peripheral arthritis, or hip joint involvement among HLA-B27 subtypes. Specific HLA-B27 subtypes were positively associated with particular clinical features of AS. AS patients with HLA-B*2705 demonstrated an older age of onset and had a higher risk of uveitis and dactylitis than did AS patients with HLA-B*2704.