J. Gu

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.

Multicenter, randomized, double-blind, controlled trial of treatment of active rheumatoid arthritis with T-614 compared with methotrexate.

OBJECTIVEnTo assess the efficacy and safety of T-614 versus methotrexate (MTX) in patients with active rheumatoid arthritis (RA).nnnMETHODSnIn this multicenter, double-blind trial, 489 patients randomly received either T-614 25 mg/day for the first 4 weeks and 50 mg/day for the subsequent 20 weeks (group 1, n = 163), T-614 50 mg/day for 24 weeks (group 2, n = 163), or MTX 10 mg/week for the first 4 weeks and 15 mg/week for the subsequent 20 weeks (n = 163). Clinical and laboratory parameters were analyzed at baseline and at 4, 10, 17, and 24 weeks.nnnRESULTSnAfter 24 weeks of treatment, the American College of Rheumatology 20% improvement criteria response rate for patients in T-614 group 2 (63.8%) was not statistically significantly different from that for patients receiving MTX treatment (62.0%), and was superior to that for patients in T-614 group 1 (50.9%). The result of the noninferiority analysis indicated that the efficacy of T-614 (50 mg/day) was not lower than that of MTX by <10%. Rheumatoid factor and IgA, IgG, and IgM demonstrated a statistically significant decrease in all groups. Frequently reported adverse events included hematologic disorder, skin reactions, gastrointestinal symptoms, and transient liver enzyme elevations in the T-614 therapy groups. Side effects in the T-614 groups were generally fewer and milder than in the MTX group, except for skin reactions. There were no prominent cardiovascular adverse events and gastrointestinal ulcers found in the T-614 groups.nnnCONCLUSIONnResults indicate that T-614 therapy 50 mg/day is effective and well tolerated, and represents a new option for the treatment of patients with active RA.

Evaluation of quality of life using ASQoL questionnaire in patients with ankylosing spondylitis in a Chinese population

The purpose of this study was to evaluate the reliability of Chinese version of the ankylosing spondylitis quality of life questionnaire (ASQoL) for AS patients. All the enrolled AS patients should fulfill five questionnaires (BASDAI, BASFI, DFI, BAS-G and ASQoL) by himself, then the investigators did physical examination of the patients, fulfilling BASMI. Physical function has a strong correlation with QoL in patients with AS. In different disease activity groups, ASQoL had a correlation with BASFI, especially in the moderate activity group (γxa0=xa00.66, Pxa0<xa00.0001). All four questionnaires in entanacept treatment group improved distinctly on week 6 and 12 comparing to baseline. There were significantly correlations of changing between ASQoL and BAS-G, BASDAI and BASFI after treatment with etanercept in AS patients. The Chinese ASQoL questionnaire is valuable to evaluate the activity of AS patients and effect of biologic agent treatment in patients with AS. It is a good generic instrument to measure QoL in patients with AS in China.

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 [pu2003=u20030.001, odds ratio (OR)u2003=u20031.54, 95% confidence interval (CI)u2003=u20031.19–1.20; pu2003=u20030.002, respectively]. Strong linkage disequilibrium was identified between IL1B‐511, IL1B+3953 and RN4 in both patients and healthy controls (D′u2003>u20030.95). 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 (pu2003=u20033.32u2003×u200310−5, ORu2003=u20034.41, 95% CI=2.1–9.3). Clinical manifestation showed week association between RN2VNTR A2 allele and risk of peripheral arthritis (ORu2003=u20030.2, 95% CIu2003=u20030.07–0.91). 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.

Clinical features of ankylosing spondylitis may correlate with HLA-B27 polymorphism

The objective of this study is to investigate the relationship between clinical features of ankylosing spondylitis (AS) and HLA-B27 status or its subtypes. Clinical data and blood samples were collected with patients’ informed consent. Luminex liquid array combining polymerase chain reaction-sequence specific oligonucleotide probe was used to do the low-resolution HLA-B genotype typing. Polymerase chain reaction-sequence specific primer was applied to do the high resolution HLA-B27 typing. In 98 subjects, 93 were HLA-B27 positive, of which three subtypes were detected: B*2704 (nxa0=xa076), B*2705 (nxa0=xa012), and B*2715 (nxa0=xa05). The onset age for B27 negative and positive group was 28xa0±xa07.9 and 21.1xa0±xa06.2xa0years, respectively (χ2xa0=xa0−2.047, Pxa0=xa00.041). The onset age for B*2704, B*2705 and B*2715 group was 20.45xa0±xa04.50, 26.67xa0±xa09.95 and 17.8xa0±xa011.12xa0years, respectively (χ2xa0=xa07.888, Pxa0=xa00.019). No significant difference was found between B27 positive and negative group, or among three B27 subtypes groups for other clinical features. In conclusion, the clinical features of AS may be correlated with HLA-B27 status and its polymorphism.

A comparison study of a recombinant tumor necrosis factor receptor:Fc fusion protein (rhTNFR:Fc) and methotrexate in treatment of patients with active rheumatoid arthritis in China.

The objective of this study is to evaluate the efficacy and safety of rhTNFR:Fc: a recombinant tumor necrosis factor receptor:Fc fusion protein compared with methotrexate (MTX) in patients with rheumatoid arthritis in China. We treated 238 patients with active rheumatoid arthritis with either twice weekly subcutaneous injection rhTNFR:Fc (25xa0mg) or weekly oral MTX (mean 15xa0mg per week) for 24xa0weeks (registration number: 2003L01264). Clinical responses were defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology (ACR-N). As compared with MTX-treated patients, more patients who received rhTNFR:Fc had ACR20 improvement in disease activity during the first 2xa0weeks (Pxa0<xa00.05). Similarly, more patients treated with rhTNFR:Fc having ACR20, ACR50, ACR70 improvement in disease activity during 8xa0weeks (Pxa0<xa00.05). At the end of 12-week treatment, patients received rhTNFR:Fc also had significant improvement at ACR20 (Pxa0<xa00.05). Compared with oral MTX, patients received rhTNFR:Fc also had significant improvement at ACR70 at the end of 24xa0weeks treatment (Pxa0<xa00.05). In conclusion, compared with oral MTX subcutaneous injection, rhTNFR:Fc acted more rapidly to release symptoms and signs of active RA in Chinese patients, and well tolerated in patients with rheumatoid arthritis in China.

Comparison of expectations of physicians and patients with rheumatoid arthritis for rheumatology clinic visits: a pilot, multicenter, international study.

To describe and compare expectations of patients with rheumatoid arthritis (RA) and their physicians with regard to what is most important to achieve during a rheumatology clinic visit.

Anti-TNF therapy in patients with HBV infection—analysis of 87 patients with inflammatory arthritis

This study aims to investigate the incidence of hepatitis B virus (HBV) reactivation in inflammatory arthritis (IA) patients with HBV infection using anti-tumor necrosis factor (TNF) agents and evaluate the efficacy of antiviral therapy in reducing the risk of viral reactivation in chronic HBV infection. IA patients using anti-TNF agents from six centers were enrolled. Their HBV infection conditions and ALT and HBV-DNA levels were monitored periodically. Among the six chronic hepatitis B patients, HBV reactivation was found in two patients without antivirus prophylaxis and no viral replication was detected in the other four patients with antivirus prophylaxis. In the 31 inactive carriers, the increase of viral load was detected in 6 of 22 (27.3xa0%) patients without antiviral prophylaxis, and there was no viral reactivation in the other 9 patients with antiviral prophylaxis. HBV reactivation was not found in the 50 patients with resolved HBV infection. It is suggested that anti-TNF therapy might increase the risk of HBV reactivation in patients with chronic HBV infection, and antiviral prophylaxis could effectively decrease the risk. Anti-TNF agents seem to be safe in patients with resolved HBV infection.