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Introduction: This article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators. Methods: This integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years). Results: Median treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan–Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs. Conclusion: Rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA. Trial Registration: ClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373. [ABSTRACT FROM AUTHOR]

Abstract Introduction This article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators. Methods This integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years). Results Median treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan–Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs. Conclusion Rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA. Trial Registration ClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

Regulatory T cells (Tregs) are a very specialized subset of T lymphocytes: their main function is controlling immune responses during inflammation. T-regs involvement in autoimmune and immune-mediated rheumatic diseases is welldescribed. Here, we critically review the up-to-date literature findings on the role of Tregs in spondyloarthropathies, particularly in ankylosing spondylitis (AS), a polygenic inflammatory rheumatic disease that preferentially affects the spine and the sacroiliac joints. Genetics discoveries helped in elucidating pathogenic T-regs gene modules and functional involvement. We highlight T-regs tissue specificity as crucial point, as T-regs might have a distinct epigenomic and molecular profiling depending on the different site of tissue inflammation. Furthermore, we speculate about possible therapeutic interventions targeting, or enhancing, Treg cells in spondyloarthropathies. [ABSTRACT FROM AUTHOR]

Background: The link between ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) is well-established, with concurrent prevalence estimates ranging from 5–10%. However, there are still significant gaps in our understanding, and a comprehensive treatment guideline for these co-diagnosed patients has yet to be established. Our objective was to explore patterns of treatment alterations following the diagnosis of AS in patients previously diagnosed with IBD, and vice versa. Additionally, we sought to determine how these modifications influence clinical outcomes in both conditions. Methods: This retrospective data-based cohort study included patients with coexisting IBD and AS that were diagnosed between the years 2009–2022 and were followed by the gastroenterology and the rheumatology units of the Sheba Medical Center, Israel. The data were extracted from the electronic health record and included demographic information, medication history, treatment modification at the time of second diagnosis, and the characteristics and activity of both IBD and AS at the index time and at the 3-month mark. Results: The study included a total of 68 patients, with a male predominance (40 patients, 59%). The median age was 43 years (IQR 31–55) and 78% had Crohn's disease (CD). The median duration between the diagnosis of the first disease to the second one was 4 years (IQR 1–9.5). A significant proportion of patients (85%) underwent treatment modification at their second diagnosis. Out of the total cohort, 28% initiated biological therapy, 17.6% switched their biologic regimen, and 16.2% discontinued NSAIDS. Patients who underwent biologic modifications at time of the second diagnosis (the initiation/switch/augmentation of a concurrent regimen) experienced significantly higher rates of clinical improvement in either IBD or AS at the 90-day follow-up compared to patients who did not (68% vs. 32%, p = 0.004), and biologic modification was found to be an independent predictor for clinical improvement (OR 3.69, CI 1.08–12.58, p = 0.037). Conclusions: Our findings suggest that biologic therapy modification at the time of the second diagnosis was associated with a higher rate of improvement in AS/IBD at the 90-day follow-up. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) are a very specialized subset of T lymphocytes: their main function is controlling immune responses during inflammation. T-regs involvement in autoimmune and immune-mediated rheumatic diseases is well-described. Here, we critically review the up-to-date literature findings on the role of Tregs in spondyloarthropathies, particularly in ankylosing spondylitis (AS), a polygenic inflammatory rheumatic disease that preferentially affects the spine and the sacroiliac joints. Genetics discoveries helped in elucidating pathogenic T-regs gene modules and functional involvement. We highlight T-regs tissue specificity as crucial point, as T-regs might have a distinct epigenomic and molecular profiling depending on the different site of tissue inflammation. Furthermore, we speculate about possible therapeutic interventions targeting, or enhancing, Treg cells in spondyloarthropathies.

Abstract Background Secukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients. Methods We retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment. Results Eighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients. Conclusion In a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.

Aims: To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. Methods: We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared. Results: The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion: In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137.

Background: Ankylosing spondylitis (AS) is an inflammatory disease that affects the spine and sacroiliac joints and is connected with the human leukocyte antigen (HLA)- B27. Late-onset AS is characterized by severedisease-marked elevation of laboratory measurements of inflammation, and more frequent involvement of the peripheral joints and the cervical spine as compared with early-onset ASObjective:This topic aimed to study the clinical, radiological, and biological profile of Algerian patients presenting Late-Onset Ankylosing Spondylitis in comparison with patientswith Early-Onset Ankylosing Spondylitis. Methods: 292 patients diagnosed with AS at the level of rehabilitation department of Hassani AEK hospital of Sidi bel abbes region were enrolled. Studied parameters were: age, disease duration, morning stiffness, joint involvements, laboratory data, disease activity, and treatments. All data were processed and analyzed via SPSS 20.0 (Statistical Package for the Social Sciences, IBM Corporation, Chicago, IL August 2011). Results: A total of 247 patients had early-onset AS, while 45 had late-onset AS. The Age Onset Ankylosing Spondylitis was associated significantly with age and disease duration p<0.0001, the average mean duration morning stiffnesswas higher in a group of late-onset age 8.00±0.000 years VS 6.91±4.288 years. However, acute inflammation was more noted in theLoAS group (93.3% Accelerated ESR and 60% positive CRP) and 93.3% of positive HLAB27 was noted in this late group with p=0. 049. Whereas, the group of early-onset age suffered more from their cervical 40.4% and lumbar 74.4% and, theywere the most affected in their peripheral joints (knees affection 14.1% vs 0% and hips affection 32.9% vs 6.7 %, p=0.033). Furthermore, high disease activity indices were more noted in this young group (BASDAI 2.984±1.942 VS 2.194±0.774 and ASDASCRP 2.659±1.309VS 2.106±1.091). Uveitis (AAU) was the most common comorbidity reported in both groups and the Sulfasalazine and Humira treatment was the most received in each group but the methotrexate treatment was more used by the early-onset AS p=0.038.Conclusion: In our study, the late-onset group exhibits higher levels of inflammation and more positive HLAB27 than the early group, which was more affected by extra-articular damage, lumbar pain, and peripheral joints. The late and early age onset groups had different AS characteristics. [ABSTRACT FROM AUTHOR]

Our objective was to analyze and assess the extra-articular manifestations (EAMs) associated with the ankylosing spondylitis in Western Algeria. 292 patients diagnosed with AS at the level of rehabilitation department of Hassani Abdelkader Hospital of Sidi Bel Abbes region were enrolled. Studied parameters were: age, gender, disease duration, disease age onset, morning stiffness, joint involvements, laboratory data, disease activity, and treatments. All data were processed and analyzed via SPSS 22.0. 105) Algerian AS patients with EAMs) and 187 without EAMs were involved. The average disease duration was of 7.72 ± 4.970 and 6.55 ± 3.613 years in the EAMs and without EAMs groups, respectively. The group without EAMs suffered more from their lumbar (77%) and high inflammatory parameters (63.1% CRP positive), and most of them were smokers 20 (10.7%). However, EAMs patients' suffered the most from their joint (20% Vs 9.6 had knees affection and 41.9% Vs 25.7% had hips affection, respectively). High disease activity was more noted in EAMs group (52.4% VS 43.3%). Uveitis (AAU) and psoriasis (PsO) were the most common EAMs reported in AS patients and were significantly associated with radiological joint damage and duration morning stiffness p<0.05. In AS Algerian patients, uveitis was the most common reported EAMs with higher radiological joint damage, high inflammatory parameters and high disease activity score. [ABSTRACT FROM AUTHOR]

Background: Fused hips with spine stiffness in ankylosing spondylitis (AS) reduce spinopelvic mobility. We aimed to assess spinopelvic mobility pattern and acetabular anteversion in AS after total hip arthroplasty (THA). Material and methods: Ninety-four stiff hips in 58 AS individuals (mean age: 37.05) who underwent THA between 2012 and 2018 with a modified lateral approach were included. Twenty-three hips were fused, and 71 hips had mean flexion of 37.67°. Pelvic tilt, pelvic inclination, sacral slope (SS), and lumbar lordosis were correlated with THA, and functional outcomes were assessed at 34.6-month mean follow-up. Results: Thirty-seven had a stuck sitting pattern with stuck standing seen in 4 individuals. SS standing before and after THA were 25.08° and 27.30°. SS sitting was 8.99° compared to 16.80°. SS from sitting to standing was reduced (17.7°) in 17 individuals. Spine stiffness in extension was seen in 4 out of 37. Mean acetabular inclination after THA was 42.67°, and acetabular anteversion was 17.48°. Flexion after THA improved to mean 98.47°. Changes in SS from sitting to standing were correlated with THA (r-value: 0.93, P-value: .0001). The Harris Hip Score improved from 25.31 to 82.39 (P-value

Background: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, with pathological characteristics of bone erosion, inflammation of attachment point, and bone ankylosis. Due to the ossified intervertebral disc and ligament, pedicle subtraction osteotomy (PSO) is one of the mainstream surgeries of AS-related thoracolumbar kyphosis, but the large amount of blood loss and high risk of instrumental instability limit its clinical application. The purpose of our study is to propose a new transpedicular vertebral body compression osteotomy (VBCO) in PSO to reduce blood loss and improve stability. Methods: A retrospective analysis was performed on patients with AS-related thoracolumbar kyphosis who underwent one-level PSO in our hospital from February 2009 to May 2019. A total of 31 patients were included in this study; 6 received VBCO and 25 received eggshell vertebral body osteotomy. We collected demographic data containing gender and age at diagnosis. Surgical data contained operation time, estimated blood loss (EBL), and complications. Radiographic data contained pre-operative and follow-up sagittal parameters including chin brow-vertical angle (CBVA), global kyphosis (GK), thoracic kyphosis (TK), and lumbar lordosis (LL). A typical case with L2-PSO was used to establish a finite element model. The mechanical characteristics of the internal fixation device, vertebral body, and osteotomy plane of the two osteotomy models were analyzed under different working conditions. Results: The VBCO could provide comparable restoring of CBVA, GK, TK, and LL in the eggshell osteotomy procedure (all p > 0.05). The VBCO significantly reduced EBL compared to those with eggshell osteotomy [800.0 ml (500.0-1,439.5 ml) vs. 1,455.5 ml (1,410.5-1,497.8 ml), p = 0.033]. Compared with the eggshell osteotomy, VBCO showed better mechanical property. For the intrapedicular screw fixation, the VBCO group had a more average distributed and lower stress condition on both nails and connecting rod. VBCO had a flattened osteotomy plane than the pitted osteotomy plane of the eggshell group, showing a lower and more average distributed maximum stress and displacement of osteotomy plane. Conclusion: In our study, we introduced VBCO as an improved method in PSO, with advantages in reducing blood loss and providing greater stability. Further investigation should focus on clinical research and biomechanical analysis for the application of VBCO. [ABSTRACT FROM AUTHOR]

Background: This study explores the association of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios with the 3-month treatment response and persistence of tumor necrosis factor-alpha (TNF-α) blockers in patients with ankylosing spondylitis (AS). Methods: This retrospective cohort study investigated 279 AS patients who were newly initiated on TNF-α blockers between April 2004 and October 2019 and 171 sex- and age-matched healthy controls. Response to TNF-α blockers was defined as a reduction in the Bath AS Disease Activity Index of ≥50% or 20 mm, and persistence referred to the time interval from the initiation to discontinuation of TNF-α blockers. Results: Patients with AS had significantly increased NLR, MLR, and PLR ratios as compared to controls. The frequency of non-response at 3 months was 3.7%, and TNF-α blockers' discontinuation occurred in 113 (40.5%) patients during the follow-up period. A high baseline NLR but not high baseline MLR and PLR showed an independently significant association with a higher risk of non-response at 3 months (OR = 12.3, p = 0.025) and non-persistence with TNF-α blockers (HR = 1.66, p = 0.01). Conclusions: NLR may be a potential marker for predicting the clinical response and persistence of TNF-α blockers in AS patients. [ABSTRACT FROM AUTHOR]

Protein phosphatase magnesium‐dependent 1A (PPM1A), serine/threonine protein phosphatase, in sera level was increased in patients with ankylosing spondylitis (AS). Preosteoblasts were differentiated actively to matured osteoblasts by intracellular PPM1A overexpression. However, it was unclear whether extracellular PPM1A contributes to the excessive bone‐forming activity in AS. Here, we confirmed that PPM1A and runt‐related transcription factor 2 (RUNX2) were increased in facet joints of AS. During osteoblasts differentiation, exogenous PPM1A treatment showed increased matrix mineralization in AS‐osteoprogenitor cells accompanied by induction of RUNX2 and factor forkhead box O1A (FOXO1A) protein expressions. Moreover, upon growth condition, exogenous PPM1A treatment showed an increase in RUNX2 and FOXO1A protein expression and a decrease in phosphorylation at ser256 of FOXO1A protein in AS‐osteoprogenitor cells, and positively regulated promoter activity of RUNX2 protein‐binding motif. Mechanically, exogenous PPM1A treatment induced the dephosphorylation of transcription factor FOXO1A protein and translocation of FOXO1A protein into the nucleus for RUNX2 upregulation. Taken together, our results suggest that high PPM1A concentration promotes matrix mineralization in AS via the FOXO1A‐RUNX2 pathway. [ABSTRACT FROM AUTHOR]

BackgroundThis study aimed to investigate the safety and efficacy of the halo-vest in the treatment of cervical fracture in patients with ankylosing spondylitis (AS) and kyphosis.MethodsFrom May 2017 to May 2021, 36 patients with cervical fractures with AS and thoracic kyphosis were included in this study. The patients with cervical spine fractures with AS underwent preoperative reduction by halo-vest or skull tractions. Instrumentation internal fixation and fusion surgery were then performed. The level of cervical fractures, the operative duration, blood loss, and treatment outcomes were investigated preoperatively and postoperatively.ResultsA total of 25 cases were included in the halo-vest group and 11 cases were included in the skull tractions group. The intraoperative blood loss and the surgery duration were significantly less in the halo-vest group than in the skull traction group. A comparison of American Spinal Injury Association scores at admission and final follow-up showed that the neurological function of patients improved in both groups. All patients had reached solid bony fusion during the follow-up.ConclusionThis study presented a unique approach to use halo-vest treatment fixation of unstable cervical fracture in patients with AS. The patient should also have early surgical stabilization with a halo-vest to correct spinal deformity and avoid worsening of neurological status.

Background: The relationship between Ankylosing Spondylitis (AS) and the risk of stroke is complex. Therefore, we utilized Two-Sample Mendelian randomization to examine the probable causal link between these two features. Methods: The genetic instruments linked to AS were chosen from a summarylevel genetic data set from the FinnGen consortium in people of European ancestry (1462 cases and 164,682 controls). Stroke and its subtypes were selected as outcomes, and the MEGASTROKE consortium population was used to identify the genetic associations of AS on stroke (40,585 cases and 406,111 controls), ischemic stroke (IS) (34,217 cases and 406,111 controls), and its subtypes including large artery stroke (LAS) (4373 cases and 146,392 controls), small vessel stroke (SVS) (5386 cases and 192,662 controls), and cardioembolic stroke (CES) (7193 cases and 204,570 controls). Intracerebral hemorrhage (ICH) (1687 cases and 201,146 controls) data set from the FinnGen consortium was also used. To obtain the casual estimates, the inverse variant weighted (IVW) method was mainly used. By examining the heterogeneity and pleiotropy of particular single nucleotide polymorphisms (SNPs), the robustness of the results was also examined. Results: There was no evidence found to prove the correlation between genetically predicted AS and stroke (odds ratio [OR] 1.014; 95% confidence interval [CI] 0.999-1.031; P = 0.063), ICH (OR 1.030; 95% CI 0.995-1.067; P = 0.090), and IS (OR 1.013; 95% CI 0. 998-1.030; P = 0.090). In terms of the different subtypes of IS, there was strong evidence of positive causal inferences on CES (OR 1.051; 95% CI 1.022-1.081; P = 0.001), and suggestive evidence of positive causal inferences on LAS (OR 1.042; 95% CI 1.003-1.082; P = 0.033), while it was not significant for SVS (OR 1.010; 95% CI 0.975-1.047; P = 0.563). Conclusion: This study suggests that the possible causative impact of genetically predicted AS on stroke may be restricted to the CES and LAS subtypes. [ABSTRACT FROM AUTHOR]

Abstract Background Ankylosing spondylitis (AS) is a common chronic inflammatory spondyloarthropathy. It is considered in traditional Chinese medicine (TCM) that the pathogenesis of AS is mainly due to Yang deficiency of kidney governor meridian and internal prosperity of cold evil. Thunder-fire moxibustion is a kind of moxibustion that is characterized in abundance in drug composition, high heat radiation, and strong penetration. Thunder-fire moxibustion on the spinal segment of the governor meridian in treating AS seems compatible with the main pathogenesis of kidney deficiency and governor meridian cold. The trial aims to explore the efficacy of thunder-fire moxibustion in patients with AS of kidney deficiency and governor meridian cold and its influence on bone metabolism, through a prospective randomized trial. Methods Sixty patients with AS of kidney deficiency and governor meridian cold will be recruited and randomly assigned to the treatment group (thunder-fire moxibustion three times a week plus basic treatment) and the control group (basic treatment) at the Center of TCM of Beijing Luhe Hospital Affiliated to Capital Medical University (Beijing, China). Each patient will be treated for 4 weeks. The primary outcome is the efficacy of TCM syndrome, and the secondary outcome indexes will include the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Short-Form-36 Questionnaire (SF-36), tumor necrosis factor-α (TNF-α), and receptor activator of nuclear factor-κB ligand (RANKL). TNF-α and RANKL with observation will be determined once respectively before and after treatment, while the other indexes will be observed once prior to the treatment, 2 weeks post-treatment, and at the end of the treatment. Side effects will be recorded and analyzed as well. Inter-group comparison and analysis will be performed based on the intention-to-treat set and per-protocol set. Discussion This prospective randomized trial will help verify the efficacy of thunder-fire moxibustion in treating AS of kidney deficiency and governor meridian cold, discuss preliminarily its mechanism in treating this disease, and provide high-quality evidences for scientific researches on clinical treatment with thunder-fire moxibustion against AS. Trial registration Chinese Clinical Trial Registry ChiCTR2100044227 . Registered on 12 March 2021

Abstract Background Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity. The objective of this study was to compare gut dysbiosis frequency between controls, non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS) patients and investigate whether gut dysbiosis is cross-sectionally associated with axSpA disease activity, physical function, mobility, or pain. Methods Gut dysbiosis was assessed by 16SrRNA analysis of feces from 44/88 nr-axSpA/AS patients (ASAS/mNY criteria) without inflammatory bowel disease (IBD) and 46 controls without IBD or rheumatic disease. The GA-map™ Dysbiosis Test was used, grading gut microbiota aberrations on a 1-5 scale, where ≥3 denotes dysbiosis. Proportions with dysbiosis were compared between the groups. Furthermore, standard axSpA measures of disease activity, function, mobility, and pain were compared between patients (nr-axSpA and AS combined) with and without dysbiosis, univariately, and adjusted for relevant confounders (ANCOVA). Results Gut dysbiosis was more frequent in AS than controls (36% versus 17%, p=0.023), while nr-axSpA (25% dysbiosis) did not differ significantly from either AS or controls. Univariately, most axSpA measures were significantly worse in patients with dysbiosis versus those without: ASDAS-CRP between-group difference 0.6 (95% CI 0.2–0.9); BASDAI 1.6 (0.8–2.4); evaluator’s global disease activity assessment (Likert scale 0–4) 0.3 (0.1–0.5), BASFI 1.5 (0.6–2.4), and VAS pain (cm) 1.3 (0.4–2.2). Differences remained significant after adjustment for demographics, lifestyle factors, treatments, gut inflammation (fecal calprotectin ≥50 mg/kg), and gut symptoms, except for VAS pain. BASMI and CRP were not associated with dysbiosis. Conclusion Gut dysbiosis, more frequent in AS patients than controls, is associated with worse axSpA disease activity and physical function, seemingly irrespective of both gut inflammation and treatments. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA.

BackgroundTo evaluate gender differences in disease activity and health status (HS) in patients with radiographic axial spondyloarthritis (r-axSpA)/ankylosing spondylitis (AS).MethodsAncillary analysis of the MIDAS study, an observational, non-interventional, cross-sectional and retrospective multicenter nationwide study to assess disease activity and its relationship with HS in clinical practice. Adult patients with AS diagnosis, fulfilling ASAS and modified New York criteria, treated for ≥3 months upon study inclusion according to clinical practice were included. The primary outcome was “disease control” assessed by the percentage of patients in remission and low disease activity (BASDAI and ASDAS-CRP scores). HS was evaluated using the ASAS health index (ASAS-HI). Patients' responses and characteristics were analyzed by gender.ResultsWe analyzed 313 patients with AS, 237 (75.7%) males and 76 (24.3%) females. A total of 202 (64.5%) patients had adequate disease control (BASDAI < 4); 69.2% of males [mean (SD) BASDAI 2.9 (2.1)] and 50.0% of females [mean (SD) BASDAI 3.8 (2.4); p = 0.01]. According to ASDAS-CRP, 57.5% of patients were adequately controlled (ASDAS-ID +ASDAS-LDA); 138 (58.2%) males and 42 (55.3%) females. The mean (SD) ASDAS-CRP was 1.9 (1.1); being 1.9 (1.0) in males and 2.0 (1.1) in females. Overall, the impact of AS on HS was low to moderate [mean (SD) ASAS-HI 5.8 (4.4)]; being 5.5 (4.4) for males and 6.8 (4.2) for females (p = 0.02).ConclusionThis study showed a higher proportion of females with AS and active disease using the BASDAI definition. When using the ASDAS-CRP definition these differences by gender were less pronounced. The impact of disease activity on HS appears to be higher in females than males.

Vitamin D deficiency is related with susceptibility or progression of various autoimmune diseases. The aim of the study was to assess potential relations between single nucleotide polymorphisms (SNPs) in the vitamin D receptor-coding gene (VDR): rs1544410 (BsmI), rs2228570 (FokI), rs731236 (TaqI), rs7975232 (ApaI), and disease activity in patients with axial spondyloarthritis (axSpA) undergoing anti-TNF therapy. The VDR rs731236 CT genotype was statistically more common among female patients (p = 0.027). An improvement of CRP equal to or higher than 50% after 3 months of anti-TNF therapy was observed for rs2228570 T allele (p = 0.002). After 6 months, CRP improvement equal to or higher than 75% was related to presence of the rs1544410 AA genotype (p = 0.027) and the rs731236 CC homozygotes (p = 0.047). Baseline BASDAI values were lower in individuals with the rs2228570 TT genotype (p = 0.036) and rs7975232 C allele (p = 0.029). After 6 months of treatment, lower BASDAI values were observed in AC heterozygotes (p = 0.005). The same AC genotype was more frequently detected in patients with remission (BASDAI ≤ 2) (p = 0.001) and in those achieving BASDAI improvement equal to or higher than 75% (p = 0.006). In conclusion, VDR SNPs were found to relate to CRP and BASDAI values at different time points of anti-TNF therapy. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a common inflammatory spondyloarthritis affecting the spine and sacroiliac joint that finally results in sclerosis of the axial skeleton. Aside from human leukocyte antigen B27, transcriptomic biomarkers in blood for AS diagnosis still remain unknown. Hence, this study aimed to investigate credible AS-specific mRNA biomarkers from the whole blood of AS patients by analyzing an mRNA expression profile (GSE73754) downloaded Gene Expression Omnibus, which includes AS and healthy control blood samples. Weighted gene co-expression network analysis was performed and revealed three mRNA modules associated with AS. By performing gene set enrichment analysis, the functional annotations of these modules revealed immune biological processes that occur in AS. Several feature mRNAs were identified by analyzing the hubs of the protein-protein interaction network, which was based on the intersection between differentially expressed mRNAs and mRNA modules. A machine learning-based feature selection method, SVM-RFE, was used to further screen out 13 key feature mRNAs. After verifying by qPCR, IL17RA, Sqstm1, Picalm, Eif4e, Srrt, Lrrfip1, Synj1 and Cxcr6 were found to be significant for AS diagnosis. Among them, Cxcr6, IL17RA and Lrrfip1 were correlated with severity of AS symptoms. In conclusion, our findings provide a framework for identifying the key mRNAs in whole blood of AS that is conducive for the development of novel diagnostic markers for AS. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes spinal inflammation and fusion. Although the cause of AS is unknown, genetic factors (e.g., HLA-B27) and environmental factors (e.g., sex, age, and infection) increase the risk of AS. Current treatments for AS are to improve symptoms and suppress disease progression. There is no way to completely cure it. High blood cholesterol and lipid levels aggravate the symptoms of autoimmune diseases. We applied hyperlipidemia drugs ezetimibe and rosuvastatin to AS mice and to PBMCs from AS patients. Ezetimibe and rosuvastatin was administered for 11 weeks to AS model mice on the SKG background. Then, the tissues and cells of mice were performed using flow cytometry, computed tomography, immunohistochemistry, and immunofluorescence. Also, the normal mouse splenocytes were cultured in Th17 differentiation conditions for in vitro analysis such as flow cytometry, ELISA and RNA sequencing. The 10 AS patients' PBMCs were treated with ezetimibe and rosuvastatin. The patients' PBMC were analyzed by flow cytometry and ELISA for investigation of immune cell type modification. Ezetimibe caused substantial inhibition for AS. The present study showed that ezetimibe inhibits Th17 cell function, thereby slowing the progression of AS. It is well known that statins are more effective in reducing blood lipid concentrations than ezetimibe, however, our results that ezetimibe had a better anti-inflammatory effect than rosuvastatin in AS. This data suggests that ezetimibe has an independent anti-inflammatory effect independent of blood lipid reduction. To investigate whether ezetimibe has its anti-inflammatory effect through which signaling pathway, various in vitro experiments and RNA sequencing have proceeded. Here, this study suggests that ezetimibe can be an effective treatment for AS patients by inhibiting Th17 differentiation-related genes such as IL-23R and IL-1R. Thus, this study suggests that ezetimibe has therapeutic potential for AS through inhibition of Th17 differentiation and the production of pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to detect the cerebral blood flow (CBF) values changes in patients with ankylosing spondylitis (AS) and to evaluate the correlation between the CBF values and the specific clinical characteristics. Materials and methods: Forty-eight patients with AS (43 male and 5 female) and 42 healthy controls (HCs) (38 male and 4 female) were recruited. Three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) was performed on a 3.0T magnetic resonance imaging (MRI). CBF values were obtained on the Philips post-processing workstation based on arterial spin labeling (ASL) data. The twosample t-test was used to compare CBF differences. The correlation between CBF values and specific clinical characteristics of AS was evaluated. Results: The AS group showed increased CBF values in the right precentral gyrus, the left inferior frontal gyrus, and the left temporal pole compared with HCs the AS group also showed decreased CBF values in the left precuneus and the left superior occipital gyrus compared with HCs. There were no significant correlations between the CBF values and the clinical characteristics including total back pain (TBP), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Conclusion: Patients with AS displayed CBF changes compared with HCs using 3D-PCASL. These results may enhance our understanding of the neural substrates of AS and provide evidence of AS-related neurological impairment. [ABSTRACT FROM AUTHOR]

Objective: To define the link of HLA-B27 with Spondyloarthritis (SPA) among the study population. Study Design: Cross-sectional study. Place and Duration of Study: Rheumatology Department Pak-Emirates Military Hospital (PEMH) Rawalpindi Pakistan, from Jun 2019 to Jan 2020. Methodology: Patients assumed to be suffering from spondyloarthritis (Spa), reporting for routine follow-up at subject OPD, were enrolled. Socio-demographic and clinical variables were measured with HLA-typing. Results: Among 550 subjects; age and BMI scores were 31.15±10.399 (18-63 years) and 23.39±4.19 (17.2-35.0 kg/m2), respectively. 391 (71.1%) patients were found positive for HLA-B27, which was significantly more amongst 20-40 years aged (p=0.003), those with non-professional education (p=0.003), associated with raised CRP(C-reactive protein, p<0.001) and ESR(erythrocyte sedimentation rate, p<0.001), with 3-6 years since the onset of symptoms (p<0.001), up to 2 years delay in diagnosis(p<0.001), peripheral arthritis(p 0.008), having co-morbidities (p=0.011), less DAL (daily activities of life, p<0.001) with no significant impact of gender, SEC (socio-economic class), pain severity, co-morbidities and formal exercise. Severe pain was stated more by females (p=0.008), low SEC (p=0.003) and overweight patients with BMI 25-29.9 (p=0.001). Conclusion: There is a strong association between HLA-B27 and spondyloarthritis (Spa), predominance in the 2nd and third decade, and no gender predilection. Auxiliary exploration would be valuable to recognize the predominant subtypes of the HLA-B27 allele in Pakistani patients with spondyloarthritis (Spa). [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to identify trajectories of radiographic progression of the spine over time and use them, along with associated clinical factors, to develop a prediction model for patients with ankylosing spondylitis (AS).MethodsData from the medical records of patients diagnosed with AS in a single center were extracted between 2001 and 2018. Modified Stoke Ankylosing Spondylitis Spinal Scores (mSASSS) were estimated from cervical and lumbar radiographs. Group-based trajectory modeling classified patients into trajectory subgroups using longitudinal mSASSS data. In multivariate analysis, significant clinical factors associated with trajectories were selected and used to develop a decision tree for prediction of radiographic progression. The most appropriate group for each patient was then predicted using decision tree analysis.ResultsWe identified three trajectory classes: class 1 had a uniformly increasing slope of mSASSS, class 2 showed sustained low mSASSS, and class 3 showed little change in the slope of mSASSS but highest mSASSS from time of diagnosis to after progression. In multivariate analysis for predictive factors, female sex, younger age at diagnosis, lack of eye involvement, presence of peripheral joint involvement, and low baseline erythrocyte sedimentation rate (log) were significantly associated with class 2. Class 3 was significantly associated with male sex, older age at diagnosis, presence of ocular involvement, and lack of peripheral joint involvement when compared with class 1. Six clinical factors from multivariate analysis were used for the decision tree for classifying patients into three trajectories of radiographic progression.ConclusionWe identified three patterns of radiographic progression over time and developed a decision tree based on clinical factors to classify patients according to their trajectories of radiographic progression. Clinically, this model holds promise for predicting prognosis in patients with AS.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes spinal inflammation and fusion. Although the cause of AS is unknown, genetic factors (e.g., HLA-B27) and environmental factors (e.g., sex, age, and infection) increase the risk of AS. Current treatments for AS are to improve symptoms and suppress disease progression. There is no way to completely cure it. High blood cholesterol and lipid levels aggravate the symptoms of autoimmune diseases. We applied hyperlipidemia drugs ezetimibe and rosuvastatin to AS mice and to PBMCs from AS patients. Ezetimibe and rosuvastatin was administered for 11 weeks to AS model mice on the SKG background. Then, the tissues and cells of mice were performed using flow cytometry, computed tomography, immunohistochemistry, and immunofluorescence. Also, the normal mouse splenocytes were cultured in Th17 differentiation conditions for in vitro analysis such as flow cytometry, ELISA and RNA sequencing. The 10 AS patients’ PBMCs were treated with ezetimibe and rosuvastatin. The patients’ PBMC were analyzed by flow cytometry and ELISA for investigation of immune cell type modification. Ezetimibe caused substantial inhibition for AS. The present study showed that ezetimibe inhibits Th17 cell function, thereby slowing the progression of AS. It is well known that statins are more effective in reducing blood lipid concentrations than ezetimibe, however, our results that ezetimibe had a better anti-inflammatory effect than rosuvastatin in AS. This data suggests that ezetimibe has an independent anti-inflammatory effect independent of blood lipid reduction. To investigate whether ezetimibe has its anti-inflammatory effect through which signaling pathway, various in vitro experiments and RNA sequencing have proceeded. Here, this study suggests that ezetimibe can be an effective treatment for AS patients by inhibiting Th17 differentiation-related genes such as IL-23R and IL-1R. Thus, this study suggests that ezetimibe has therapeutic potential for AS through inhibition of Th17 differentiation and the production of pro-inflammatory cytokines.

Introduction: It is important to recognise inflammatory back pain (IBP) for early diagnosis of ankylosing spondylitis (AS). The aims of this study were to develop a valid, reliable Bengali IBP tool and to assess the performance of different IBP criteria sets, including Calin, Berlin set 8a and 7b, and new Assessment of SpondyloArthritis International Society (ASAS) expert criteria, in radiographic axial spondyloarthritis (axSpA) and nonradiographic axSpA. Method: This case-control study was performed in three phases. The first phase involved development of an IBP tool by adding the fifth parameter of ASAS expert criteria to the National Health and Nutrition Examination Survey (NHANES) 2009–2010 arthritis questionnaires; the second phase assessed reliability by test-retest statistics among 87 participants at a 5-day interval. Finally, according to the imaging arm of ASAS axSpA classification criteria, 50 patients with axSpA were included as cases while 50 patients with chronic mechanical back pain (MBP) were included as a control. Results: The presence of IBP with SpA versus patients with MBP, detected by Calin criteria, were 76.0% versus 10.0%, by Berlin 8a were 72.0% versus 6.0%, by Berlin 7b were 58.0% versus 12.0%, and by ASAS were 64.0% versus 18.0%, respectively. Results suggested the Calin criteria set has the highest sensitivity (76.0%) and Berlin set 8a has the highest specificity (78.9%) in the differentiation of IBP from MBP. Conclusion: The performance of the new ASAS criteria was analogous to the other existing criteria sets. The highest positive likelihood ratio and odds ratio were found for Berlin set 8a criteria. The Berlin set 8a criteria can still be used in primary care practice at the first screening because of high sensitivity.

BackgroundTo investigate the association between a history of acute anterior uveitis (AAU) and the risk of major adverse cardiovascular events (MACE) among patients with ankylosing spondylitis (AS).MethodsWe identified 38,691 newly diagnosed AS patients between 2003 and 2013 from the Taiwan National Health Insurance Research Database. The exposure group was defined as people with uveitis diagnosis by ophthalmologist before AS diagnosis date. The incidence of MACE in patients with AS according to the International Classification of Diseases, Ninth Revision. We randomly selected a comparison group without a history of AAU at a 1:4 ratio matched by age, sex, and index year in relation to the risk of developing MACE. We used cox proportional hazard regression model to compare the risk of MACE between groups, shown as adjusted hazard ratios (aHRs) with 95% confidence intervals (CI). Further subgroup analysis and sensitivity tests were also performed.ResultsThere were 3,544 patients in the AAU group and 14,176 patients in the non-AAU group. The aHR of MACE for the AAU group was 0.79 (95% CI = 0.57–1.10) at a 1:4 ratio for age, sex and index year. Sensitivity analyses using various adjustment variables showed consistent results. Cox proportional hazard regression model demonstrated that use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of MACE in this cohort (HR = 3.44; 95% CI = 2.25–5.25).ConclusionThis cohort study showed that subjects with AAU was not associated with the risk of MACE among AS patients, compared to non-AAU controls.

Background: This study explores the association of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios with the 3-month treatment response and persistence of tumor necrosis factor-alpha (TNF-α) blockers in patients with ankylosing spondylitis (AS). Methods: This retrospective cohort study investigated 279 AS patients who were newly initiated on TNF-α blockers between April 2004 and October 2019 and 171 sex- and age-matched healthy controls. Response to TNF-α blockers was defined as a reduction in the Bath AS Disease Activity Index of ≥50% or 20 mm, and persistence referred to the time interval from the initiation to discontinuation of TNF-α blockers. Results: Patients with AS had significantly increased NLR, MLR, and PLR ratios as compared to controls. The frequency of non-response at 3 months was 3.7%, and TNF-α blockers’ discontinuation occurred in 113 (40.5%) patients during the follow-up period. A high baseline NLR but not high baseline MLR and PLR showed an independently significant association with a higher risk of non-response at 3 months (OR = 12.3, p = 0.025) and non-persistence with TNF-α blockers (HR = 1.66, p = 0.01). Conclusions: NLR may be a potential marker for predicting the clinical response and persistence of TNF-α blockers in AS patients.

Background: Ankylosing spondylitis (AS) is a common chronic inflammatory spondyloarthropathy. It is considered in traditional Chinese medicine (TCM) that the pathogenesis of AS is mainly due to Yang deficiency of kidney governor meridian and internal prosperity of cold evil. Thunder-fire moxibustion is a kind of moxibustion that is characterized in abundance in drug composition, high heat radiation, and strong penetration. Thunder-fire moxibustion on the spinal segment of the governor meridian in treating AS seems compatible with the main pathogenesis of kidney deficiency and governor meridian cold. The trial aims to explore the efficacy of thunder-fire moxibustion in patients with AS of kidney deficiency and governor meridian cold and its influence on bone metabolism, through a prospective randomized trial.Methods: Sixty patients with AS of kidney deficiency and governor meridian cold will be recruited and randomly assigned to the treatment group (thunder-fire moxibustion three times a week plus basic treatment) and the control group (basic treatment) at the Center of TCM of Beijing Luhe Hospital Affiliated to Capital Medical University (Beijing, China). Each patient will be treated for 4 weeks. The primary outcome is the efficacy of TCM syndrome, and the secondary outcome indexes will include the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Short-Form-36 Questionnaire (SF-36), tumor necrosis factor-α (TNF-α), and receptor activator of nuclear factor-κB ligand (RANKL). TNF-α and RANKL with observation will be determined once respectively before and after treatment, while the other indexes will be observed once prior to the treatment, 2 weeks post-treatment, and at the end of the treatment. Side effects will be recorded and analyzed as well. Inter-group comparison and analysis will be performed based on the intention-to-treat set and per-protocol set.Discussion: This prospective randomized trial will help verify the efficacy of thunder-fire moxibustion in treating AS of kidney deficiency and governor meridian cold, discuss preliminarily its mechanism in treating this disease, and provide high-quality evidences for scientific researches on clinical treatment with thunder-fire moxibustion against AS.Trial Registration: Chinese Clinical Trial Registry ChiCTR2100044227 . Registered on 12 March 2021. [ABSTRACT FROM AUTHOR]

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease with serious consequences and a high rate of morbidity and mortality, In our previous work, we reveal the key features of proteins in new-onset ankylosing spondylitis patients. Material and Methods: Ankylosing spondylitis (AS) is a chronic inflammatory condition that affects the spine, and inflammation plays an essential role in AS pathogenesis. The inflammatory process in AS, however, is still poorly understood due to its intricacy. Systematic proteomic and phosphorylation analyses of peripheral blood mononuclear cells (PBMCs) were used to investigate potential pathways involved in AS pathogenesis. Results: Liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis was performed and discovered 782 differentially expressed proteins (DEPs) and 122 differentially phosphorylated proteins (DPPs) between 9 new-onset AS patients and 9 healthy controls. The DEPs were further verified using parallel reaction monitoring (PRM) analysis. PRM analysis verified that 3 proteins (HSP90AB1, HSP90AA1 and HSPA8) in the antigen processing and presentation pathway, 6 proteins (including ITPR1, MYLK and STIM1) in the platelet activation pathway and 10 proteins (including MYL12A, MYL9 and ROCK2) in the leukocyte transendothelial migration pathway were highly expressed in the PBMCs of AS patients. Conclusion: The key proteins involved in antigen processing and presentation, platelet activation and leukocyte transendothelial migration revealed abnormal immune regulation in patients with new-onset AS. These proteins might be used as candidate markers for AS diagnosis and new therapeutic targets, as well as elucidating the pathophysiology of AS. [ABSTRACT FROM AUTHOR]

Abstract Background Ankylosing spondylitis (AS) is characterized by excessive production of inflammatory cytokines. Recent evidence suggests that inflammation underlies the neurodegenerative process of Parkinson’s disease (PD). Whether AS has an influence on the development of PD is unclear. We aimed to examine a relationship, if any exists between AS and PD. Methods A population-based matched cohort study was performed using data from the 2000–2010 Taiwan National Health Insurance database. 6440 patients with AS and 25,760 randomly selected, age- and sex-matched controls were included in this study. The risk of PD in the AS cohort was evaluated by using a Cox model. Results This study revealed a positive association between AS and the risk of PD regardless of sex and age (aHR 1.75, p

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory disease with serious consequences and a high rate of morbidity and mortality, In our previous work, we reveal the key features of proteins in new-onset ankylosing spondylitis patients.Material and MethodsAnkylosing spondylitis (AS) is a chronic inflammatory condition that affects the spine, and inflammation plays an essential role in AS pathogenesis. The inflammatory process in AS, however, is still poorly understood due to its intricacy. Systematic proteomic and phosphorylation analyses of peripheral blood mononuclear cells (PBMCs) were used to investigate potential pathways involved in AS pathogenesis.ResultsLiquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis was performed and discovered 782 differentially expressed proteins (DEPs) and 122 differentially phosphorylated proteins (DPPs) between 9 new-onset AS patients and 9 healthy controls. The DEPs were further verified using parallel reaction monitoring (PRM) analysis. PRM analysis verified that 3 proteins (HSP90AB1, HSP90AA1 and HSPA8) in the antigen processing and presentation pathway, 6 proteins (including ITPR1, MYLK and STIM1) in the platelet activation pathway and 10 proteins (including MYL12A, MYL9 and ROCK2) in the leukocyte transendothelial migration pathway were highly expressed in the PBMCs of AS patients.ConclusionThe key proteins involved in antigen processing and presentation, platelet activation and leukocyte transendothelial migration revealed abnormal immune regulation in patients with new-onset AS. These proteins might be used as candidate markers for AS diagnosis and new therapeutic targets, as well as elucidating the pathophysiology of AS.

Spondyloarthropathies (SpAs), are a group of chronic inflammatory diseases with a number of genetic, physiopathological, clinical and radiological features. Ankylosing spondylitis (AS) is the most common type of spondylo-arthropathies, and >90.0% of patients with ankylosing spondylitis are human leukocyte antigen-B27 (HLA-B2 7)-positive. In recent years, non-HLA genetic factors have been reported to have an effect on ankylosing spondylitis. MicroRNAs (miRNAs), are endogenous non coding RNA molecules containing 18-23 nucleotides that play a role in the post-transcriptional regulation of gene expression. In this study, we aimed to determine the expression levels of miRNAs associated with T- and B-cell differentiation/stimulation in peripheral blood mononuclear cells and their relationship with the etiology of the AS in patients and healthy controls. In a molecular study, peripheral blood mononuclear cell isolation, and total RNA isolation were performed first. In the second step, cDNA synthesis and quantitative real-time PCR (qPCR) expression analysis were completed. Ultimately, in the patient and control group, the expression levels of miR-142-5p and miR-143 were found to be significantly different (p

Objectives: Anti-tumor necrosis factor (TNF) agents have been regarded as the most effective treatment for ankylosing spondylitis (AS) so far. However, economic factors limited the prescription of original biologicals in China. Yisaipu® is a biosimilar for etanercept as pre fill syringes (PFS), which has entered China's national medical insurance catalog for more than 10 yr and was widely used because it greatly reduced the economic burden of AS patients. Yisaipu® is provided subcutaneous injection in hospital setting only. We collected clinical data of AS patients before, during and after COVID-19 epidemic, in an attempt to investigate the advantages and disadvantages of original biologicals and Yisaipu® during regular follow up and COVID-19 epidemic. Methods: AS patients who received original biologicals or Yisaipu® in our department for more than 1 yr were included in our study. General data, demographic characteristics, disease activity, quality of life and medical compliance were collected from regular visits. The patients were followed up through telephone interviews from April 20th to 27th, 2020 about the overall impact of the COVID-19 epidemic. Results: There was no significant difference in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) between the two groups. Health Assessment Questionnaire for Spondyloarthropathies (HAQ-s) showed that Yisaipu® group was superior to original biological group in terms of eating, gripping and driving. In addition, the medical cost of Yisaipu® was lower than that of original biologicals. The overall impact of the COVID-19 epidemic on patients of original biological group was comparatively smaller than that on Yisaipu® group. Conclusions: Yisaipu® provided AS patients with an economical selection during regular follow-up, while original biologicals had certain advantages in the COVID-19 epidemic setting, including a longer time interval between two drug administrations and the self-injection dose form of medication. [ABSTRACT FROM AUTHOR]

Objectives: Anti-tumor necrosis factor (TNF) agents have been regarded as the most effective treatment for ankylosing spondylitis (AS) so far. However, economic factors limited the prescription of original biologicals in China. Yisaipu® is a biosimilar for etanercept as pre fill syringes (PFS), which has entered China’s national medical insurance catalog for more than 10 yr and was widely used because it greatly reduced the economic burden of AS patients. Yisaipu® is provided subcutaneous injection in hospital setting only. We collected clinical data of AS patients before, during and after COVID-19 epidemic, in an attempt to investigate the advantages and disadvantages of original biologicals and Yisaipu® during regular follow up and COVID-19 epidemic.Methods: AS patients who received original biologicals or Yisaipu® in our department for more than 1 yr were included in our study. General data, demographic characteristics, disease activity, quality of life and medical compliance were collected from regular visits. The patients were followed up through telephone interviews from April 20th to 27th, 2020 about the overall impact of the COVID-19 epidemic.Results: There was no significant difference in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) between the two groups. Health Assessment Questionnaire for Spondyloarthropathies (HAQ-s) showed that Yisaipu® group was superior to original biological group in terms of eating, gripping and driving. In addition, the medical cost of Yisaipu® was lower than that of original biologicals. The overall impact of the COVID-19 epidemic on patients of original biological group was comparatively smaller than that on Yisaipu® group.Conclusions: Yisaipu® provided AS patients with an economical selection during regular follow-up, while original biologicals had certain advantages in the COVID-19 epidemic setting, including a longer time interval between two drug administrations and the self-injection dose form of medication.

Background: patients with Ankylosing Spondylitis (AS) usually suffer from diagnostic delay. having symptoms up to several years before correct diagnosis, leading to psychological distress, physical and healthcare burden. Objective: To measure the period of diagnostic delay of AS and explore the main causes of diagnostic delay. Patients and Methods: A forty -eight consecutive patients (41 males, 7 females), the mean age 34.4 ±8.54 years (ranging from 18 to 58 years) with AS who met the modified New York 1984 criteria were enrolled in this cross sectional study, which have been conducted at Merjan teaching hospital, Rheumatologic and rehabilitation out-patient department in Babylon from period January 2018 to July 2019. The diagnostic delay was defined as the interval between appearance of first symptoms and correct diagnosis of AS was me) for each patient. Full detailed history of each patient about her/his journey of previous diagnosis and treatment measures were recorded.asured (in years Results: The mean of diagnostic delay was 8.47±6.15 years in males, and 10.1± 8.62 years in females. The most common missed diagnoses contributing to delay diagnosis of AS were: non-specific back pain (22 patients, 45.8%), degenerative disease (lumbar spondylosis) (10 patients, 20.8 %) disc prolapse (12 patients, 25%), sacroiliac sprain (2 patients 4.16%), rheumatoid arthritis (1 patient, 2.17%), and chronic brucellosis (1 patient 2.17%). Conclusion: Most patients had obvious diagnostic delay prior to definite AS diagnosis which could have been avoided with earlier intervention. [ABSTRACT FROM AUTHOR]

The breadth of bone lesion types seen in spondyloarthritis is unprecedented in medicine and includes increased bone turnover, bone loss and fragility, osteitis, osteolysis and erosion, osteosclerosis, osteoproliferation of soft tissues adjacent to bone and spinal skeletal structure weakness. Remarkably, these effects can be present simultaneously in the same patient. The search for a potential unifying cause of effects on the skeleton necessarily focuses on inflammation arising from the dysregulation of immune response to microorganisms, particularly dysregulation of TH17 lymphocytes, and the dysbiosis of established gut and other microbiota. The compelling notion that a common antecedent pathological mechanism affects existing bone and tissues with bone-forming potential (entheses), simultaneously with variable effect in the former but bone-forming in the latter, drives basic research forward and focuses our awareness on the effects on these bone mechanisms of the increasing portfolio of targeted immunotherapies used in the clinic. [ABSTRACT FROM AUTHOR]