O. Jin

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.

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.

Disorders of MicroRNAs in Peripheral Blood Mononuclear Cells: As Novel Biomarkers of Ankylosing Spondylitis and Provocative Therapeutic Targets

Background. MicroRNAs can potentially regulate every aspect of cellular activity. In this study, we investigated whether AS pathogenesis involves microRNAs disorders. Result. The expression of 2 microRNAs, hsa-miR-126-3p and hsa-miR-29a, was significantly lower in active AS group before etanercept therapy than in control group. Marched fold changes of them were 3.76 and 16.22. Moreover, expressions of hsa-miR-126-3p and hsa-miR-29a were dramatically upregulated after 12-weeks etanercept treatment. Fold changes were 2.20 and 3.18. All regulations of microRNAs expression mentioned before were statistically significant (fold change >2 and P < 0.05). The expression disorders of the 2 microRNAs did not statistically significantly correlated with BASDAI, CRP, and ESR. Conclusion. AS pathogenesis involved dysregulation of microRNAs. Hsa-miR-126-3p and hsa-miR-29a will probably become the potential biomarkers and provocative therapeutic targets of AS.

Epidemiological comparison of clinical manifestations according to HLA-B*27 carrier status of Chinese Ankylosing Spondylitis patients

The aim of the study was to investigate and compare the clinical manifestations between HLA-B27(+) and HLA-B27(-) ankylosing spondylitis (AS) patients in order to obtain knowledge of the impact of HLA-B27 status on AS, and to inform clinical treatment. A nationwide epidemiological investigation was performed from November 2008 to October 2010. The demographic data and clinical characteristics, and the status of HLA-B27 were collected using questionnaires and laboratory assay, respectively. A total of 2144 patients (78.5% males and 78.4% HLA-B27(+) AS patients) participated in this study. The percentages of males, patients with family history, and involvement of lumbar spine, thoracic spine and hip joints, were observed to be significantly higher in the HLA-B27(+) AS patients than in their HLA-B27(-) AS peers.

Evaluation of Assessment of Spondyloarthritis International Society classification criteria for axial spondyloarthritis in Chinese patients with chronic back pain: results of a 2‐year follow‐up study

To evaluate the diagnotic value of the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axial spondyloarthritis (SpA) in Chinese patients with chronic back pain and without radiographic sacroiliitis in a 2‐year follow‐up study.

A Genome-Wide SNP Linkage Analysis Suggests a Susceptibility Locus on 6p21 for Ankylosing Spondylitis and Inflammatory Back Pain Trait

Objectives To screen susceptibility loci for ankylosing spondylitis (AS) using an affected-only linkage analysis based on high-density single nucleotide polymorphisms (SNPs) in a genome-wide manner. Patients and Methods AS patients from ten families with Cantonese origin of China were enrolled in the study. Blood samples were genotyped using genomic DNA derived from peripheral blood leukocytes by Illumina HumanHap 610-Quad SNP Chip. Genotype data were generated using the Illumina BeadStudio 3.2 software. PLINK package was used to remove non-autosomal SNPs and to further eliminate markers of typing errors. An affected-only linkage analysis was carried out using both non-parametric and parametric linkage analyses, as implemented in MERLIN. Result Seventy-eight AS patients (48 males and 30 females, mean age: 39±16 years) were enrolled in the study. The mean age of onset was 23±10 years and mean duration of disease was 16.7±12.2 years. Iritis (2/76, 2.86%), dactylitis (5/78, 6.41%), hip joint involvement (9/78, 11.54%), peripheral arthritis (22/78, 28.21%), inflammatory back pain (IBP) (69/78, 88.46%) and HLA-B27 positivity (70/78, 89.74%) were observed in these patients. Using non-parameter linkage analysis, we found one susceptibility locus for AS, IBP and HLA-B27 in 6p21 respectively, spanning about 13.5Mb, 20.9Mb and 21.2Mb, respectively No significant results were found in the other clinical trait groups including dactylitis, hip involved and arthritis. The identical susceptibility locus region spanning above 9.44Mb was detected in AS IBP and HLA-B27 by the parametric linkage analysis. Conclusion Our genome-wide SNP linkage analysis in ten families with ankylosing spondylitis suggests a susceptibility locus on 6p21 in AS, which is a risk locus for IBP in AS patients.

Serum from patients with ankylosing spondylitis can increase PPARD, fra-1, MMP7, OPG and RANKL expression in MG63 cells

OBJECTIVES: To explore the effects of serum from patients with ankylosing spondylitis on the canonical Wnt/β-catenin pathway and to assess whether the serum has an osteogenic effect in MG63 cells. METHODS: MG63 cells were cultured with serum from 45 ankylosing spondylitis patients, 30 healthy controls, or 45 rheumatoid arthritis patients. The relative PPARD, fra-1, MMP7, OPG and RANKL mRNA levels were measured using quantitative real-time polymerase chain reaction. Associations between gene expression and patient demographics and clinical assessments were then analyzed. RESULTS: MG63 cells treated with serum from ankylosing spondylitis patients had higher PPARD, fra-1, MMP7 and OPG gene expression than did cells treated with serum from controls or rheumatoid arthritis patients (all p<0.05). RANKL expression was higher in MG63 cells treated with serum from patients with ankylosing spondylitis or rheumatoid arthritis than in those treated with serum from controls (both p<0.05). The OPG/RANKL ratio was also higher in MG63 cells treated with serum from ankylosing spondylitis patients than in those treated with serum from controls (p<0.05). No associations were found between the expression of the five genes and the patient demographics and clinical assessments (all p>0.05). CONCLUSIONS : Serum from ankylosing spondylitis patients increases PPARD, fra-1, MMP7, OPG and RANKL expression and the OPG/RANKL ratio in MG63 cells; these effects may be due to the stimulatory effect of the serum on the Wnt pathway.

SAT0262 7 Cases of Chinese Juvenile Relapsing Polychondritis and Systemic Review

Background Relapsing polychondritis (RP) is a rare systemic autoimmune disease characterized by recurrent episodes of inflammation and progressive destruction of cartilaginous tissues. Juvenile RP (<18 years) mentioned more severe than adult as previous reports. Objectives Our work is to study the clinical and prognostic features of Juvenile Relapsing polychondritis (RP). Methods 7 RP cases from 1994–2013 in our hospital were reviewed and compared with 51 international juvenile cases and 158 Chinese adult case series reported from 1985–2013 including clinical features, systemic involvement, differential diagnosis and prognosis. Results 1)Average age at the onset was 15.1 years old, the mean age at first symptoms was 15.1 months and female-male ratio was 0.4:1, 6 of 7 had been misdiagnosed. 2)The incidences of arthritis (100%: 53%), nasal chondritis (1%: 53%), laryngotracheal syndromes (86%: 68%), auricular chondritis (86%: 67%), cardiovascular involvement (14%: 10%) and autoimmune diseases (14%: 5%) were higher than in Chinese adult except skin (20%: 46%). 3) Our juvenile RP patients had more severe in respect toocular inflammation (57%: 40–47%), arthritis (100%, 71–90%), cardiovascular (14%: 3–10%) and skin involvement (20%:10–11%) than Caucasian juvenile RP. Conclusions Our juvenile RP series were more severe than Chinese adult RP as the same as in Caucasians and has its unique characteristics in spite of sharing most clinical features with case series in literature. Disclosure of Interest None declared

THU0274 Upregulation of NOD2 Involved in The Inflammatory Response by Activation of MAPK Signaling Pathway in Lupus Nephritis

Background Nucleotide-binding oligomerization domain (NOD) - containing 2 (NOD2) is a NOD - like receptors (NLRs) which plays important role in immune regulation and inflammatory response. There are increasing evidences to show that NOD2 may contribute to the development of numerous auto inflammatory and autoimmune disorders. However, their role in lupus nephritis (LN) is not known. Here, we explored the role of NOD2 in LN. Objectives However, their role in lupus nephritis (LN) is not known. Here, we explored the role of NOD2 in LN. Methods Immunohistochemistry was applied to observe the expression of NOD2 in renal biopsies. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of NOD2 mRNA in the biopsies. In vitro studies, HK-2 cells (renal tubular epithelial cell-line) were cultured with different inflammatory stimulation, western blot was used to investigate their expression of NOD2 and the following activation of MAPK pathway signals (ERK1/2, p38 and JNK), real-time qPCR was applied to observe the mRNA levels of downstream pro-inflammatory mediators (IL-1b, IL-8, MCP-1, TGF-b1, IL-6). Results (1) Immunohistochemistry staining demonstrated that the expression of NOD2 in LN is higher than that of normal control (P=0.002), and the mRNA level of NOD2 in renal tissue of LN patients was higher than that of normal control (P=0.001). (2) In vitro studies, the urine and serum from onset LN patients can significantly promote higher NOD2 expression in HK2 cells than that from healthy control (P<0.001). In addition, TGF-b1, LPS and muramyl dipeptide (MDP) can also induce higher NOD2 expression in HK2 cells (P<0.001, respectively). (3) The activation of NOD2 increased phosphorylation of ERK1/2, p38 and JNK. Moreover, the activation of NOD2 induced the release of pro-inflammatory mediators including IL-1b, IL-8, MCP-1, TGF-b1, IL-6. Conclusions Our study showed NOD2 expression was increased in LN patients. The activation of NOD2 can promote the activation of MAPK signaling pathway and release of downstream pro-inflammatory mediators. NOD2 may participate in the pathogenesis of LN. Disclosure of Interest None declared