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We aimed to investigate the clinical, diagnostic, and imaging features of patients with late onset axial spondyloarthritis (SpA) with initial symptom manifestation aged over 45 years. Participants with axial SpA were consecutively recruited. Clinical, demographic, blood, and imaging parameters were compared between the groups with early (≤45 years) and late onset (45 years) at a cross-sectional level. Logistic regressions were used to determine the independent associations with axial SpA with late onset. A total of 455 participants were recruited. Among them, 70 (15.4%) had late onset disease. Multivariate analyses showed that axial SpA with late onset was associated with higher C-reactive protein based ankylosing spondylitis disease activity index (ASDAS-CRP) (B = 0.10; P = .04), higher intensity of spinal inflammation as measured by maximum apparent diffusion coefficient (spinal ADC max) (B = 0.27; P = .03) and mean ADC (spinal ADC mean) (B = 0.30; P = .004), lower modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) (B = -0.12; P = .02), more tender joint count (B = 0.12; P = .02), and fewer inflammatory back pain (IBP) (OR = 0.26; P.001). Axial SpA with late onset had higher clinical disease activity, higher intensity of spinal MRI inflammation, less radiographic damage, and more tender joint count. There was also less inflammatory back pain, which could make the diagnosis more difficult.

Background Bronchial asthma (referred to as asthma in the present study) is the most common chronic airway inflammatory disease in childhood. The present study aimed to investigate the effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on VDR expression, which is closely associated with asthmatic airway smooth muscle cells (ASMCs), and explored its role and mechanism in the Rho-kinase signaling pathway. Methods The acute asthma model was induced by ovalbumin (OVA) and pertussis bacillus, and ASMCs obtained from asthmatic rats were cultured in vitro. These cells were randomly divided into five groups: control (N) group, TNF-α (TNF) group, 1,25-(OH)2D3 (VD) group, dexamethasone (DXM) group, and 1,25-(OH)2D3 + DXM (L) group. The protein expression levels of VDR, ROCK, MLC20 and P-MLC20 were detected by western blot, and the mRNA expression levels of VDR, ROCK, MLC20 and P-MLC20 were detected by real-time quantitative PCR. Results The expression of ROCK, MLC20 and P-MLC20 in each treatment group were significantly lower, when compared to the TNF group (P 0.05) that in the N group. Conclusions The regulation mechanism of 1,25-(OH)2D3 in alleviating asthma should be correlated to its regulation of the expression of related signaling molecules in the Rho-kinase signaling pathway, and this effect may be achieved by regulating the mRNA and protein expression of the VDR gene.

Tumor necrosis factor inhibitor (TNFi) has been applied in the treatment of ankylosing spondylitis (AS) for many years but still with an unmed need due to inefficacy or intolerance. Current treatment guideline recommended the use of IL-17 inhibitors over a second TNFi in patients with primary nonresponse to the first TNFi. We herein review the present available IL-17 inhibitors including secukinumab (SEC), ixekizumab (IXE), brodalumab and bimekizumab (BKZ) in clinical trials of AS. Therapeutic response and safe profile have been discussed in detail for each drug. Overall, IL-17 inhibitors were proved to be alternatives for biologic disease-modifying anti-rheumatic drugs (bDMARDs) in AS, which might be safer for tuberculosis while candida infection should be monitored in long term treatment.

Ixekizumab (IXE) is a high affinity IgG4 approved for the treatment of ankylosing spondylitis (AS). Recently, two phase III randomized clinical trials (COAST-V, COAST-W) showed significant and sustained improvements in signs and symptoms of AS as evaluated by ASAS40 response.

Adipose-derived mesenchymal stem cells (A-MSCs) are promising cellular therapies for the treatment of immune-mediated diseases. Non-gene editing technologies can improve the immune regulatory function of A-MSCs. Our preliminary experiments revealed that an active form of vitamin B6—pyridoxal-5′-phosphate (PLP)—plays an important role in regulating gene expression and cytokine secretion in A-MSCs in vivo. To further clarify the effect of PLP on receptors and cytokines related to the immune regulatory function of A-MSCs, a series of experiments were designed to verify the relationships between PLP and A-MSCs in vitro. Initially, A-MSCs were obtained, and cytokine secretion and the expression of IDO1, NF-κB, and Toll-like receptors in PLP-stimulated A-MSCs were evaluated. In addition, coculture was used to detect A-MSCs-mediated apoptosis of CD3+CD8+ T lymphocytes. These results showed that A-MSCs stimulated with PLP were highly proliferative, consistent with their pluripotent capacity. Further, the surface receptors TLR3, TLR4, IDO1, and NF-κB were upregulated, while TLR6 was downregulated. Concurrently, A-MSCs preconditioned with PLP had the greatest inhibitory effect on CD3+CD8+ T lymphocyte proliferation, indicating that PLP altered the immune regulatory function of A-MSCs through the regulation of TLRs and IDO1 expression.

Ankylosing spondylitis (AS) has been associated with an increased cardiovascular disease (CVD) risk, with current guidelines recommending multiple CVD-related risk assessment strategies. CVD risk prediction using a scoring model with lipids might be another promising alternative, for which ultrasound screening for subclinical atherosclerosis may be considered together with surrogate markers. Theoretically, tumor necrosis factor inhibitors (TNFi), which are known to inhibit endothelial activation and inflammation caused by the disease and underlying metabolic dysfunction, might prevent microvascular events. In this narrative review, we summarized the evidence of TNFi effects on CVD in AS. Although early case reports revealed that CVD occurred during TNFi treatment, more recent evidence shows that it could be successfully treated. Studies of TNFi on lipid changes and subclinical atherosclerosis have shown controversial results, possibly due to genetic predisposition, differences in affinity for membrane-bound TNF leading to insufficient inhibition of inflammation or primary failure response to TNFi, and not enough follow-up time to identify potential significance. Overall, patients vulnerable to CVD could benefit from long-term administration of TNFi when inflammation is under control. Besides healthy lifestyle modification, traditional CVD risk factors and metabolic syndrome-related diseases should be further assessed and treated if necessary.

BACKGROUND: Bronchial asthma (referred to as asthma in the present study) is the most common chronic airway inflammatory disease in childhood. The present study aimed to investigate the effect of 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] on VDR expression, which is closely associated with asthmatic airway smooth muscle cells (ASMCs), and explored its role and mechanism in the Rho-kinase signaling pathway. METHODS: The acute asthma model was induced by ovalbumin (OVA) and pertussis bacillus, and ASMCs obtained from asthmatic rats were cultured in vitro. These cells were randomly divided into five groups: control (N) group, TNF-α (TNF) group, 1,25-(OH)(2)D(3) (VD) group, dexamethasone (DXM) group, and 1,25-(OH)(2)D(3) + DXM (L) group. The protein expression levels of VDR, ROCK, MLC20 and P-MLC20 were detected by western blot, and the mRNA expression levels of VDR, ROCK, MLC20 and P-MLC20 were detected by real-time quantitative PCR. RESULTS: The expression of ROCK, MLC20 and P-MLC20 in each treatment group were significantly lower, when compared to the TNF group (P0.05) that in the N group. CONCLUSIONS: The regulation mechanism of 1,25-(OH)(2)D(3) in alleviating asthma should be correlated to its regulation of the expression of related signaling molecules in the Rho-kinase signaling pathway, and this effect may be achieved by regulating the mRNA and protein expression of the VDR gene.

Background: Magnetic resonance imaging (MRI) is important in the management of axial spondyloarthritis (SpA). However, many MRI lesions are not exclusive to axial SpA. Further characterization of these lesions may lead to better clinical decisions. Objective: The objective of this study was to compare the frequency of individual spinal MRI lesions between axial SpA and noninflammatory back pain. The factors associated with individual lesions in participants with axial SpA were also determined. Design: This was a cross-sectional observational study. Methods: MRI lesions in 447 participants with axial SpA and 122 participants with noninflammatory back pain were compared using the propensity score adjustment method. Individual lesions included discovertebral lesions (DVL), Modic type 1 lesions, DVL without Modic type 1 lesions, facet joint lesions, costovertebral joint lesions, corner inflammatory lesions (CIL), and fatty corner lesions (FCL). The factors associated with the lesions were determined using regression analyses. Results: Among participants with axial SpA, 81.9% were HLA-B27-positive, 55.0% had radiographic axial SpA, and 60.5% had radiographic features of spinal damage (mSASSS >2). Almost half (48.6% in axial SpA versus 31.1% in noninflammatory back pain) had inflammatory lesions on spinal MRI. In propensity score matching with noninflammatory back pain, axial SpA had an increased occurrence of DVL without Modic type 1 lesion (OR = 3.43, p = 0.01), costovertebral lesion (OR = 11.89, p = 0.02), number of CIL ( B = 1.19, p Conclusion: MRI lesions including DVL without Modic type 1, costovertebral joint lesions, CIL, and FCL were more specific in axial SpA.

Purpose: The purpose of the article is to investigate the contribution of calprotectin and factors in toll-like receptor 4/nuclear factor-κB/myeloid differentiation factor 88 (TLR4/NF-κB/MyD88) pathway in patients with idiopathic acute anterior uveitis (IAAU). Methods: In total, 72 patients with IAAU and 56 healthy individuals were enrolled. Serum calprotectin, TLR-4, and MyD88 were determined. Best-corrected visual acuity, uveitis activity grading, and macular thickness measured by optical coherence tomography were performed. Results: Serum calprotectin, TLR4, and MyD88 levels were higher in IAAU group than those in healthy individuals. Serum calprotectin level was positively correlated with uveitis activity grading and macular thickness. Receiver operating characteristic curve analysis showed serum calprotectin had larger area under curve than serum TLR4 and MyD88. Conclusions: The calprotectin and TLR4/NF-κB/MyD88 signal might contribute to the pathogenesis of IAAU and serum calprotectin might be a specific biomarker for the measurement of ocular inflammation in IAAU.

Objective The aim was to investigate the relationship between the intensity of spinal inflammation using the apparent diffusion coefficient (ADC) and radiographic progression in axial SpA. Methods This is a cross-sectional study of participants with axial SpA and back pain. Clinical, biochemical and radiological parameters were collected. The ankylosing spondylitis disease activity score (ASDAS)-CRP was determined. Radiographic progression was represented by the modified Stoke ankylosing spondylitis spine score (mSASSS). MRI with short tau inversion recovery (STIR) and diffusion-weighted imaging sequences were performed simultaneously. Inflammatory lesions on STIR were used for the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI indexes and as references in outlining regions of interest in ADC maps to produce mean (ADCmean) and maximal (ADCmax) ADC values. Univariate and multivariate linear regression analyses were used to determine independent associations between ADC and radiographic progression. Results The 84 participants with identifiable lesions on spinal ADC maps recruited were characterized by a mean (s.d.) age of 45.01 (13.68) years, long disease duration [13.40 (11.01) years] and moderate clinical disease activity [ASDAS-CRP 2.07 (0.83)]. Multivariate regression analysis using ADCmean as the independent variable showed that age (regression coefficient [B] = 0.34; P = 0.01), male sex (B = 0.25; P = 0.04) and ADCmean (B = 0.30; P = 0.01) were positively associated with mSASSS. Multivariate regression analysis using ADCmax as the independent variable showed a tendency for ADCmax to be associated with mSASSS (B = 0.21; P = 0.07). Conclusion The intensity of spinal inflammation as determined by ADC is associated with radiographic progression in participants with active axial SpA.

We read with great interest the article ‘Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial’ by Wei et al .1 As the first multicentre randomised controlled trial in patients with axial spondyloarthritis (axSpA) of brodalumab, it makes a remarkable contribution to treatment of this novel interleukin-17 (IL-17) inhibitor in two disease subtypes, which shows a great remission rate and short-term safety. However, there are some aspects that need to be discussed. First, regarding the study design, it was mentioned that the dose of 210 mg is based on the therapeutic dose of psoriasis. However, in clinical trials of psoriasis, the drug dose is usually …

We read with great interest the article by Micheroli et al 1 for comparison of effectiveness between secukinumab (SEC) and tumour necrosis factor inhibitor (TNFi) in axial spondylitis (axSpA), with evidence conform to the current recommendation in a Swiss real-world setting. According to current guidelines,2 ,3 ,4interleukin-17 inhibitor (IL-17i) or alternative TNFi are both recommended as the switch option of biological disease-modifying antirheumatic drug in patients with previous TNFi failure. Although head-to-head comparison clinical trials between IL-17 inhibition and TNF blockade have been conducted in psoriatic arthritis recently5 6 and is ongoing in axSpA, we appreciated Micheroli et al 1 for their new information in this real-world indirect comparison study. However, some issues can be further discussed. First, regarding the study design, it was not mentioned whether treatment adjustment was due to drug inefficacy or intolerability and the types of TNFi, receptor fusion protein or monoclonal antibody …

Background Immunoadsorption (IAS) has been used to treat patients with SLE for many years. Efficacy was proved for case report or series with SLE after IAS treatment, while case-control studies are so far lacking. Objectives We aim to evaluate the efficacy and safety of IAS as an addition to aggressive immunosuppressive treatment in Chinese SLE patients with severe disease activity. Methods Patients with SLE disease activity index 2000 (SLEDAI 2k) >15 were enrolled. The number of patients in IAS group and non-IAS group was 52, including 22 with lupus nephritis (LN), 10 with severe thrombocytopenia ( 9 /l), 10 with neuropsychiatric lupus and 10 with a large pericardial effusion, respectively. Observation study was performed for every individual in either group for 3 months. Corticosteroid pulse therapy (CSPT, intravenous methylprednisolone 250 mg/day for 3 days) was given to each patient consecutively, followed by a daily oral dose of 1 mg/kg bodyweight of corticosteroid. Corticosteroid were tapered by 10% every 1∼2 weeks after 4 weeks. IAS was initiated on the second day of CSPT. Other immunosuppressant included intravenous cyclophosphamide pulse therapy (IVCY, targeting 0.5 g/m 2 body surface area) every 2 weeks for 3 months. IVCY was initiated after 3 days9 of CSPT. Results In total 52 SLE patients, the improvement of C3 level, dsDNA and AnuA titer after treatment at different visits compared with baseline was discovered in both groups, while the overall changes of these markers in IAS group were all more significant than those in non-IAS group. Similar results were observed in subgroup analysis. SLEDAI score dropped significantly after 1 week of treatment both in IAS group (from 24.46±4.14 to 12.65±3.85, p=1.13×10 –27 ) and non-IAS group (from 24.46±4.07 to 14.67±3.42, p=5.41×10 –24 ), while the significance was more prominent in IAS group (p=0.004). The dosage of steroids used at 3 months was significantly lower in IAS group (13.46±4.12mg) than that in non-IAS group (15.10±3.77mg) (p=0.037). No severe side effect occurred in our study. Conclusions This is the first report of the application of phenylalanine immunoadsorption to treating patients with SLE in China. In combination with corticosteroid therapy and immunosuppressant, IAS would appear to be an effective and safe treatment optimal for SLE, without consideration of its high cost. References Stummvoll GH. Immunoadsorption (IAS) for systemic lupus erythematosus. Lupus. 2011; 20(2):115–9. [PubMed: 21303827] Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25:1271–7. [PubMed: 7138600] Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997; 40:1725. [PubMed: 9324032] Petri M, Orbai AM, Alarcόn GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug;64(8):2677–86. [PubMed: 22553077] Acknowledgement We thank the nursing team of the apheresis unit for accurate and friendly support. Disclosure of Interest None declared

Background Recent studies showed that canonical Wnt pathway and miR-29a play important roles in the pathogenesis of bone formation. Objectives We studied the levels of miR-29a and bone turnover markers in canonical Wnt pathway in ankylosing spondylitis (AS). Methods The levels of miR-29a and mRNA of bone turnover markers in canonical Wnt pathway from peripheral blood mononuclear cells were determined by real-time quantitative polymerase chain reaction in 43 patients with AS and 42 healthy controls. Correlation analysis was conducted between the levels of miR-29a and mRNA and clinical measurements using Spearman9s correlation test. Serum levels of components of canonical Wnt pathway including Dickkopf-1 (DKK-1), GSK-3β, β-catenin, alkaline phosphatase (ALP) and osteocalcin (OC) were detected using ELISA method. Results Compared to healthy controls, the levels of miR-29a, Dickkopf (DKK)-1, β-catenin and Runx2 mRNA were significantly higher in AS patients (p 0.05).The levels of DKK-1 was significantly higher in AS patients (1914.46±407.82 pg/ml) than that in healthy controls (1729.07±352.86 pg/ml) (p Conclusions The osteoblastic marker miR-29a and downstream mRNA of canonical Wnt signaling was upregulated in AS, suggesting their possible role in the new bone formation in AS. Alteration of bone turnover markers in canonical Wnt pathway was observed in AS. This might partially explain the complicated mechanism of bone formation in the disease. References Corr M. Wnt signaling in ankylosing spondylitis. Clin Rheumatol. 2014;33(6):759–62. Uderhardt S, Diarra D, Katzenbeisser J, David JP, Zwerina J, Richards W, et al. Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints. Ann Rheum Dis 2010;69:592–7. Kapinas K, Kessler CB, Delany AM. miR-29 suppression of osteonectin in osteoblasts: regulation during differentiation and by canonical Wnt signaling. J Cell Biochem 2009;108:216–24. Kapinas K, Kessler C, Ricks T, Gronowicz G, Delany AM. miR-29 modulates Wnt signaling in human osteoblasts through a positive feedback loop. J Biol Chem 2010;285:25221–31. Huang J, Song G, Yin Z, Luo X, Ye Z. Elevated miR-29a expression is not correlated with disease activity index in PBMCs of patients with ankylosing spondylitis.Mod Rheumatol 2014;24:331–4. Acknowledgement This research was supported by National Natural Science Foundation of China (81301529), Natural Science Foundation of Guangdong Province (S2013040012296), Shenzhen science and technology project (JCYJ20150331142757389) and Public Welfare Scientific Research Project of Futian District Shenzhen (FTWS201308). Disclosure of Interest None declared