Tianwang Li

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.

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 Rare Co-Segregation-Mutation in the Insulin Receptor Substrate 1 Gene in One Chinese Family with Ankylosing Spondylitis

Ankylosing spondylitis (AS; MIM 106300) is a common rheumatic disease with strong genetic components affecting approximately 0.3% of the population. The exact genetic mechanism of AS remains elusive. Our previous study showed that AS could be transmitted in an autosomal dominant inheritance mode and a 6-cM candidate region located on the chromosome 2q36.1-36.3 was mapped in a Chinese family. Mutation screening was conducted within the candidate region in the family and other AS by sequencing, and the novel mutation will be further validated in other AS families, sporadic cases and healthy controls by mass spectrometry. We identified a rare non-synonymous mutation (Arg580Gly) in insulin receptor substrate 1 (IRS1) co-segregated with disease phenotype in patients of the family, which was not found in other AS families, sporadic patients and healthy controls. In the study, we found a rare non-synonymous mutation in IRS1 co-segregation in one Chinese family with AS, which indicated a new candidate disease causative gene for AS.

AB0714 Monocytes to lymphocytes ratio is correlated with disease activity in behÇet’s disease

Background Behçet’s disease (BD) is a complex, inflammatory multisystem disorder. Since the lack of universally recognised pathognomonic laboratory test, the diagnosis relies heavily on clinical findings. Currently, the Monocytes to lymphocytes to ratio (MLR), Neutrophils to Lymphocytes ratio (NLR), Platelets to Lymphocytes ratio (PLR) and Red blood cell Distribution Width(RDW) have been demonstrated as a assessment of disease severity in many rheumatism diseases. Nevertheless, to our knowledge, only a few studies have investigated NLR, PLR, RDW in patients with BD. Objectives The aim of this study is to determine MLR, NLR, PLR and RDW in BD and to investigate their relationships with disease activity. Methods A total of 37 patients with BD fulfilling the criteria of the International Study Group for BD and 37 age and gender-matched healthy controls were enrolled in the study retrospectively. MLR, NLR, PLR, RDW, C-reactive protein(CRP) level and Erythrocyte Sedimentation Rate(ESR) level were evaluated. The correlation between the variables were tested with Pearson correlation. Area Under Curve(AUC) value, sensitivity, specificity, and the optimal cut-off values were determined using Receiver Operating characteristic Curves (ROC). According to the optimal cut off value, BD patients were divided into low-value group (<the optimal cut off value) and high value group (≥the optimal cut off value). The patient‘s clinical characteristics between the two group were compared. Results The MLR, NLR, PLR and RDW were (0.37±0.24), (2.91±1.95), (155.09±55.08) and (13.83±1.77) in BD group, while (0.18±0.04), (1.45±0.46), (115.66±28.01) and (13.07±1.19) in control group, the difference was significant (P all<0.05). MLR, NLR and PLR were all correlated positively with ESR(r=0.363, P<0.05; r=0.611, P<0.05; r=0.496, P<0.05) and CRP(r=0.713, P<0.05; r=0.785, P<0.05; r=0.394, P<0.05). RDW was not correlated with ESR and CRP. ROC curve results showed that the AUC of MLR, NLR, PLR and RDW for BD were 0.841(CI95%: 0.748–0.935), 0.815(CI95%: 0.712–0.918), 0.720(CI95%: 0.699–0.840), 0.635(CI95%: 0.505–0.765), MLR yielded a highest AUC. In addition, the optimal cut off value of MLR for BD was 0.23, with the specifity of 73.0% and sensitivity of 83.8%. In 37 BD patients, 14 belong to low MLR group, 23 belong to high MLR value group. The comparison results show that high MLR value group have higher CRP level and higher incidence of genital ulceration(P<0.05).Abstract AB0714 – Figure 1 Conclusions MLR was elevated in BD patients as compared to control group, having a close relationship with disease activity. References [1] Sariyildiz MA, Yazmalar L, Batmaz I, et al. Serum GDF-15 level inBehcet’s disease: relationships between disease activity and clinicalparameters. Int J Dermatol2016;55:1289–94 [2] Mercan R, et al. The Association Between Neutrophil/Lymphocyte Ratio and Disease Activity in Rheumatoid Arthritis and Ankylosing Spondylitis. J Clin Lab Anal. 2016; 30(5): 597–601. Acknowledgements This study was supported by A talent development fund from Guangdong Second Provincial General Hospital (No. 2014001), Medical Scientific Research Foundation of Guangdong Province(No. A2017551). Disclosure of Interest None declared

THU0010 Altered mirnas profiles in plasma-derived exosome of patients with ankylosing spondylitis by small rna-seq analysis

Background Ankylosing spondylitis (AS) is a chronic inflammatory disease, which is difficult to diagnose in the early stages. Increasing evidences have shown that MicroRNAs (miRNAs) may serve as novel biomarkers for AS. Exosome can function as vehicles to deliver miRNAs in body fluids including saliva and plasma. However, the relationship between exosome-delivered miRNAs and AS has yet to be determined. Objectives The aim of this study is to detect the altered miRNAs profiles of plasma-derived exosome in AS patients by small RNA-Seq Analysis. Methods RiboTM kit was used to isolate exosome. Small RNA Sample Pre Kit was used to build libraries in 3 AS patients and 3 healthy volunteers (HV), following by IlluminaHiSeq platform sequencing and bioinformatics analysis. Quantitative reverse-transcription PCR (qRT-PCR) was used to confirm the expression of the highly-expressed miRNA in another 10 AS patients and 10 HV, and receiver-operator characteristic (ROC) curve was used to evaluate the diagnostic value of miRNAs. Results Small RNA-Seq analysis showed that the Q30 value of HV and AS patients were higher than 95% (Fig.1-A). The amount of miRNA in HV and AS patients were (509.667±77.501) and (632.000±43.555). 80 up-regulated and 19 down-regulated exosomal miRNAs were identified in AS patients, compared with HV (|log2Ratio|>1, P <0.05) (Fig.1-B-C). The target genes of the 34 highly-expressed miRNAs from the 99 differently-expressed miRNAs were 7869, and the main function of these target genes are involved in the regulation of endocytosis and protein modification process analyzed by GO and KEGG. The qRT-PCR results indicated that the expression level of miRNA21–5P and miRNA423–5P in AS patients were (2.940±1.572) and (2.520±1.401) times higher than that of HV (Fig.1-D-E). ROC curve analysis showed that miRNA21–5P and miRNA423–5P had significant diagnostic value for AS with the AUC of 0.890 (CI95%: 0.723–1.057) and 0.835 (CI95%: 0.621–1.039) respectively (Fig.1-F). Conclusions The miRNAs profiles in plasma-derived exosome of AS patients are significant different from HV. miRNA21–5P and miRNA423–5P are higher expressed in AS patients. Thus, plasma-derived exosomal miRNAs might be reliable biomarkers to identify AS. References El MA. Extra-articular manifestations of ankylosing spondylitis: prevalence, characteristics and therapeutic implications. Eur J Intern Med, 2011, 22(6):554–60. Disclosure of Interest None declared