Alterations in peripheral T-cell and B-cell subsets in the ankylosing spondylitis patients with gut inflammation.

AIM: This study investigates changes in immune cell subsets in peripheral blood of ankylosing spondylitis (AS) patients with colitis or terminal ileitis. It aims to explore the connection between changes in lymphocyte subsets and gut inflammation, providing insights for early detection. METHODS: Overall, 50 AS patients undergoing colonoscopy were enrolled. Flow cytometry was employed to analyze lymphocyte subsets, including T and B cells, in peripheral blood. Disease activity was assessed using CRP, ESR, BASDAI, ASDAS-CRP, and ASDAS-ESR. RESULTS: Compared to AS patients without gut inflammation, those with colorectal inflammation showed a significant increase in total T cells (p < .05), an increase in exhausted CD4+ T cells (p < .05), and a decrease in Th2 cells and total Tc cells (p < .05). Notably, in AS patients with terminal ileitis, there was an increase in total B cells and classic switched B cells (p < .05), with a decrease in double-positive T cells (p < .05). However, no significant differences were observed in the distribution of Tfh-cell subpopulations (Tfh1, Tfh2, Tfh17) and Tc-cell subpopulations (Tc1, Tc2, Tc17) between AS patients with either colorectal inflammation or terminal ileitis (p > .05). We explored the relationship between disease activity scores, ESR, CRP, and lymphocyte subsets, but found no statistically significant correlation between them. CONCLUSION: Distinct immune patterns may exist in AS with different types of intestinal inflammation. Colitis in AS is primarily characterized by a significant increase in exhausted CD4+ T cells, along with a decrease in Th2 cells. In contrast, terminal ileum inflammation in AS is marked by an increase in total B cells and classic switched B cells. These findings offer new insights for early detection and therapeutic intervention.

Tuberculin skin test repetition after TNF-α inhibitors in patients with chronic inflammatory arthritis: a long-term retrospective cohort in endemic area.

OBJECTIVES: To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. METHODS: Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). RESULTS: A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6-12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6-10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5-13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 - 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. CONCLUSION: These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.

An effective strategy for treatment of severe kyphosis secondary to ankylosing spondylitis: one-level modified osteotomy combined with shoulders lifting correction method.

BACKGROUND: Severe kyphosis is a common condition in patients with advanced ankylosing spondylitis (AS). Although two-level osteotomy may serve as a potential alternative, it is often associated with increased blood loss and elevated surgical risks. To date, the optimal treatment for the challenging condition remains unclear. This study aims to introduce an effective strategy for the treatment of severe kyphosis secondary to AS, using one-level modified osteotomy combined with shoulders lifting correction method. METHODS: Seventy AS kyphosis who were treated with the strategy from 2012 to 2022, were reviewed retrospectively. All patients were followed up for a minimum duration of 2 years. Spinal and pelvic parameters were measured, including pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), lumber lordosis (LL), PI and LL mismatch (PI-LL), thoracic kyphosis, global kyphosis (GK), T1 pelvic angle (TPA), sagittal vertical axis (SVA), osteotomized vertebral angle (OVA), and chin-brow vertical angle (CBVA). Parameters of local osteotomized complex were measured and calculated, including the height of osteotomized complex and the length of spinal cord shortening. Clinical outcome was evaluated using Scoliosis Research Society-22 and Oswestry Disability Index scores. RESULTS: Seventy patients with average age of 39.8 years were followed-up for 29.3 months. Average operation time was 373.5 min, and average blood loss was 751.0 ml. Postoperatively, sagittal balance was successfully restored. GK decreased from 90.6° to 35.6°, LL decreased from 8.0° to -35.1°, TPA decreased from 56.8° to 27.8°, and SVA decreased from 24.4 cm to 8.7 cm (P < 0.05). A harmonious and matched spinopelvic alignment was achieved. PT decreased from 37.2° to 26.3°, PI-LL decreased from 54.1° to 10.2°, and SS increased from 9.2° to 19.7°(P < 0.05). Horizontal vision was obtained with postoperative CBVA of 8.8°. Average OVA correction was up to 47.3°, and the spinal cord was shortened by 24.3 mm, with a shortening rate of 36.0%. All patients demonstrated a favorable clinical outcome. No permanent nerve damage, screw loosening, rod breakage and main vascular injury were observed. One case required revision surgery due to screw cap loosening and delayed union. Solid bone fusion was achieved in all other patients. CONCLUSIONS: One-level modified osteotomy combined with shoulders lifting correction method is a safe and effective strategy for the treatment of severe AS kyphosis. This strategy offers a promising alternative for managing severe AS kyphosis, and may be particularly well-suited for individuals with concurrent osteoporosis. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Neurological Side Effects of TNF-α Inhibitors Revisited: A Review of Case Reports.

Over the past two decades, the use of tumor necrosis factor alpha (TNF-α) inhibitors has significantly improved the treatment of patients with immune-mediated inflammatory diseases. Firstly, introduced for rheumatoid arthritis, these inhibitors are currently approved and used for a variety of conditions, including ankylosing spondylitis, Crohn's disease, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, ulcerative colitis, and chronic uveitis. Despite their immense therapeutic efficacy, TNF-α inhibitors have been associated with neurological adverse effects that bring new clinical challenges. The present review collects data from multiple studies to evaluate the incidence and the relationship between TNF-α inhibitors and neurological side effects and to explore the potential underlying mechanisms of this association. Moreover, it highlights the importance of patient selection, particularly in the case of individuals with a history of demyelinating diseases, raises awareness for clinicians, and calls for ongoing research that will improve TNF-α targeting strategies and offer safer and more effective therapeutic options.

Association between serum iron status and the risk of five bone and joint-related diseases: a Mendelian randomization analysis.

Background: According to reports, iron status has been associated with the risk of bone and joint-related diseases. However, the exact role of iron status in the development of these conditions remains uncertain. Method: We obtained genetic data on iron status, specifically serum iron, ferritin, transferrin saturation (TSAT), and transferrin, as well as data on five common bone and joint-related diseases (osteoarthritis, osteoporosis, rheumatoid arthritis [RA], ankylosing spondylitis [AS], and gout) from independent genome-wide association studies involving individuals of European ancestry. Our primary approach for causal estimation utilized the inverse variance weighted (IVW) method. To ensure the reliability of our findings, we applied complementary sensitivity analysis and conducted reverse causal analysis. Result: Using the IVW method, we revealed a positive causal relationship between ferritin levels and the risk of osteoarthritis (OR [95% CI], 1.0114 [1.0021-1.0207]). Besides, we identified a protective causal relationship between serum iron levels and TSAT levels in the risk of RA (OR [95% CI] values of serum iron and TSAT were 0.9987 [0.9973-0.9999] and 0.9977 [0.9966-0.9987], respectively). Furthermore, we found a positive causal relationship between serum iron levels and the risk of AS (OR [95% CI], 1.0015 [1.0005-1.0026]). Regarding gout, both serum iron and TSAT showed a positive causal relationship (OR [95% CI] values of 1.3357 [1.0915-1.6345] and 1.2316 [1.0666-1.4221] for serum iron and TSAT, respectively), while transferrin exhibited a protective causal relationship (OR [95% CI], 0.8563 [0.7802-0.9399]). Additionally, our reverse causal analysis revealed a negative correlation between RA and ferritin and TSAT levels (OR [95% CI] values of serum iron and TSAT were 0.0407 [0.0034-0.4814] and 0.0049 [0.0002-0.1454], respectively), along with a positive correlation with transferrin (OR [95% CI], 853.7592 [20.7108-35194.4325]). To ensure the validity of our findings, we replicated the results through sensitivity analysis during the validation process. Conclusion: Our study demonstrated a significant correlation between iron status and bone and joint-related diseases.

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases. / åŒæ ·æœ¬å­Ÿå¾·å°”éšæœºåŒ–åˆ†æžæ¹¿ç–¹ä¸Žè‡ªèº«å ç–«æ€§ç–¾ç— ä¹‹é—´çš„å› æžœå ³ç³»ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: The causal relationship between eczema and autoimmune diseases has not been previously reported. This study aims to evaluate the causal relationship between eczema and autoimmune diseases. METHODS: The two-sample Mendelian randomization (MR) method was used to assess the causal effect of eczema on autoimmune diseases. Summary data from the Genome-Wide Association Study Catalog (GWAS) were obtained from the Integrative Epidemiology Unit (IEU) database. For eczema and autoimmune diseases, genetic instrument variants (GIVs) were identified according to the significant difference (P<5×10-8). Causal effect estimates were generated using the inverse-variance weighted (IVW) method. MR Egger, maximum likelihood, MR-PRESSO, and MR-RAPS methods were used for alternative analyses. Sensitivity tests, including heterogeneity, horizontal pleiotropy, and leave-one-out analyses, were performed. Finally, reverse causality was assessed. RESULTS: Genetic susceptibility to eczema was associated with an increased risk of Crohn's disease (OR=1.444, 95% CI 1.199 to 1.738, P<0.001) and ulcerative colitis (OR=1.002, 95% CI 1.001 to 1.003, P=0.002). However, no causal relationship was found for the other 6 autoimmune diseases, including systemic lupus erythematosus (SLE) (OR=0.932, P=0.401), bullous pemphigoid (BP) (OR=1.191, P=0.642), vitiligo (OR=1.000, P=0.327), multiple sclerosis (MS) (OR=1.000, P=0.965), ankylosing spondylitis (AS) (OR=1.001, P=0.121), rheumatoid arthritis (RA) (OR=1.000, P=0.460). Additionally, no reverse causal relationship was found between autoimmune diseases and eczema. CONCLUSIONS: Eczema is associated with an increased risk of Crohn's disease and ulcerative colitis. No causal relationship is found between eczema and SLE, MS, AS, RA, BP, or vitiligo.

18F-FDG positron emission tomography as a marker of disease activity and treatment response in ankylosing spondylitis and psoriatic arthritis.

The ability of 18F-FDG positron emission tomography (PET) to track disease activity and treatment response in patients with Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA) remains unclear. Here, we assessed whether 18F-FDG uptake is a marker of disease activity and treatment response in AS or PsA, and explored the ability of 18F-FDG to predict treatment response. Patients with AS (n = 16) or PsA (n = 8) who were scheduled to initiate treatment with biologics were recruited. Participants underwent a clinical evaluation and an 18F-FDG scan prior to therapy initiation. Eleven participants underwent a follow-up 18F-FDG scan 3 months post-treatment. Images were quantified using a composite measure that describes the inflammatory status of the patient. Clinically involved joints/entheses had higher 18F-FDG uptake compared to unaffected areas (median difference > 0.6, p < 0.01). Among patients with AS, pre-treatment 18F-FDG uptake was strongly associated with disease activity (r = 0.65, p = 0.006). Longitudinal 18F-FDG scans demonstrated that decreases in uptake at 3 months were associated to clinical response (ßΔgSUVmax > 8.5, p < 0.001). We found no significant association between pre-treatment 18F-FDG uptake and subsequent clinical response. 18F-FDG PET shows potential as a marker of disease activity in AS and PsA, allowing for monitorization of biological treatment efficacy in these patients.

[Robot-assisted versus traditional fluoroscopy-assisted posterior fixation in treatment of thoracolumbar fractures with ankylosing spondylitis: a retrospective study].

Objective: To compare the effectiveness of robot-assisted (RA) minimally invasive surgery versus traditional fluoroscopy-assisted (FA) open posterior fixation surgery in treating thoracolumbar fractures with ankylosing spondylitis (AS). Methods: A clinical data of 21 cases of thoracolumbar fractures with AS who met the selection criteria between December 2016 and December 2023 was retrospectively analyzed. Ten cases underwent RA minimally invasive surgery group (RA group) and 11 cases underwent FA open posterior fixation surgery (FA group). There was no significant difference in gender, age, fracture segment distribution, fracture type, time from injury to surgery, visual analogue scale (VAS) score, and American Spinal Injury Association (ASIA) grading between RA group and FA group ( P>0.05). The operation time, intraoperative blood loss, radiation exposure time, radiation dose, hospital stay, and complications of the two groups were recorded. According to Gertzbein-Robbins criteria, the accuracy of screw implantation was evaluated by CT within 1 week after surgery. During follow-up, pain and nerve function were evaluated by VAS score and ASIA grading. Results: All patients underwent surgery successfully, and there was no significant difference in operation time ( P>0.05). The intraoperative blood loss and hospital stay in the RA group were significantly less than those in the FA group ( P<0.05), and the radiation exposure time and radiation dose were significantly more than those in the FA group ( P<0.05). A total of 249 pedicle screws were implanted in the two groups, including 118 in the RA group and 131 in the FA group. According to the Gertzbein-Robbins criteria, the proportion of clinically acceptable screws (grades A and B) in the RA group was significantly higher than that in the FA group ( P<0.05). Patients in both groups were followed up 3-12 months, with an average of 6.8 months. The VAS scores of the two groups after surgery were significantly lower than those before surgery, and the differences were significant ( P<0.05). The RA group had lower scores than the fluoroscopy group at 1 week and 3 months after surgery ( P<0.05). There was no significant difference in neurological function grading between groups at 1 week and 3 months after surgery ( P>0.05). In the FA group, 1 case of deep infection and 1 case of deep vein thrombosis of lower extremity occurred, while no complication occurred in the RA group, and there was no significant difference in the incidence of complications between groups ( P>0.05). Conclusion: Both RA minimally invasive surgery and FA open posterior fixation surgery can achieve good effectiveness. Compared with the latter, the former has more advantages in terms of intraoperative blood loss, hospital stay, and accuracy of pedicle screw insertion.

Analysis of risk factors affecting postoperative neurological recovery in patients with cervical spine fracture in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease that mainly affects the spine and involves the sacroiliac and peripheral joints. Low-energy trauma can often lead to spinal fractures and spinal cord injuries (SCIs), the treatment of AS is challenging. The prognosis of neurological function in patients with AS cervical fracture and SCI is a major problem that must sought clinician attention on urgent basis. A total of 106 patients with AS cervical fractures who underwent surgical treatment at Shanghai Changzheng Hospital between August 2009 and 2021 were included in this study. All the patients were divided into 2 groups (improved group and the control group) based on their neurological function improvement at 1 year mark after the surgery. The baseline characteristics, perioperative factors, and procedural outcomes of all the patients including injury type, AS drug treatment, the injured segment, ossified anterior longitudinal ligament injury, spinal hypersignal, decompression time window, operation duration, blood loss, preoperative and postoperative American Spinal Injury Association (ASIA) score were recorded and analyzed. Among the 106 patients, 79 demonstrated improved neurological function at 1 year mark after the surgery. Binary univariate logistic regression analysis revealed significant differences in injury type (P = .018), ossified anterior longitudinal ligament injury (P = .01), operation duration (P = .002), spinal hypersignal (P = .001), preoperative ASIA score (P < .001), and prior AS drug treatment (P = .012). No significant differences were observed in the other variables (P > .05). Binary multivariate logistic regression analysis identified spinal hypersignal (OR = 37.185, P = .028), preoperative ASIA score (OR = 0.16, P = .012) and previous AS drug treatment (OR = 0.296, P = .049) as factors associated with postoperative neurological function improvement. The preoperative ASIA score and previous drug treatment of AS were identified as protective factors affecting the improvement of neurological functions in patients with AS cervical fracture after surgery. Preoperative T2-weighted spinal hypersignal was identified as an independent risk factor affecting the improvement of neurological function recovery in patients with AS cervical fracture after the surgery.

Inflammatory disease status and response to TNF blockade are associated with mechanisms of endotoxin tolerance.

The mechanisms of endotoxin tolerance (ET), which down-regulate inflammation, are well described in response to exogenous toll-like receptor ligands, but few studies have focused on ET-associated mechanisms in inflammatory disease. As blocking TNF can attenuate the development of ET, the effect of anti-TNF on the expression of key ET-associated molecules in inflammatory auto-immune disease was measured; changes in inflammatory gene expression were confirmed using an ET bioassay. The expression of immunomodulatory molecules was measured in a murine model of arthritis treated with anti-TNF and the expression of ET-associated molecules was measured in whole blood in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients, before and after therapy. The expression of ET-associated genes was also measured in RA patient monocytes before and after therapy, in anti-TNF responders and non-responders. Tnfaip3, Ptpn6 and Irak3 were differentially expressed in affected paws, spleens, lymph nodes and circulating leucocytes in experimental murine arthritis treated with anti-TNF. Prior to therapy, the expression of TNFAIP3, INPP5D, PTPN6, CD38 and SIGIRR in whole blood differed between human healthy controls and RA or AS patients. In blood monocytes from RA patients, the expression of TNFAIP3 was significantly reduced by anti-TNF therapy in non-responders. Prior to therapy, anti-TNF non-responders had higher expression of TNFAIP3 and SLPI, compared to responders. Although the expression of TNFAIP3 was significantly higher in RA non-responders prior to treatment, the post-treatment reduction to a level similar to responders did not coincide with a clinical response to therapy.

Identification of key genes with abnormal RNA methylation modification and selected m6A regulators in ankylosing spondylitis.

BACKGROUND: N6-methyladenosine (m6A) has been identified as the most abundant modification of RNA molecules and the aberrant m6A modifications have been associated with the development of autoimmune diseases. However, the role of m6A modification in ankylosing spondylitis (AS) has not been adequately investigated. Therefore, we aimed to explore the significance of m6A regulator-mediated RNA methylation in AS. METHODS: The methylated RNA immunoprecipitation sequencing (meRIP-seq) and digital RNA sequencing (Digital RNA-seq) were conducted using the peripheral blood mononuclear cells from three AS cases and three healthy controls, to identify genes affected by abnormal RNA methylation. The genes associated with different peaks were cross-referenced with AS-related genes obtained from the GeneCards Suite. Subsequently, the expression levels of shared differentially expressed genes (DEGs) and key m6A regulators in AS were evaluated using data from 68 AS cases and 36 healthy controls from two data sets (GSE25101 and GSE73754). In addition, the results were validated through quantitative polymerase chain reaction (qPCR). RESULTS: The meRIP-seq and Digital RNA-seq analyses identified 28 genes with upregulated m6A peaks but with downregulated expression, and 52 genes with downregulated m6A peaks but with upregulated expression. By intersecting the genes associated with different peaks with 2184 AS-related genes from the GeneCards Suite, we identified a total of five shared DEGs: BCL11B, KAT6B, IL1R1, TRIB1, and ALDH2. Through analysis of the data sets and qPCR, we found that BCL11B and IL1R1 were differentially expressed in AS. Moreover, two key m6A regulators, WTAP and heterogeneous nuclear ribonucleoprotein C, were identified. CONCLUSIONS: In conclusion, the current study revealed that m6A modification plays a crucial role in AS and might hence provide a new treatment strategy for AS disease.

Targeted therapies and conventional care for the treatment of ankylosing spondylitis in China: a cost-effectiveness analysis based on the network-meta analysis.

OBJECTIVE: This study aimed to evaluate the long-term cost-effectiveness of conventional care (CC) and seven first-line targeted therapies marketed in China for the treatment of patients with ankylosing spondylitis (AS)-namely secukinumab, ixekizumab, infliximab, etanercept, adalimumab and golimumab and tofacitinib-from the perspective of the Chinese health care system. METHODS: The York model was structured as a 12-week decision tree leading into two Markov models. This study set 1 year as a recurring cycle and a lifetime timeframe for the model. Primary model outcomes included the costs in Chinese yuan (CNY), health outcomes in quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of ¥89,358 (equal to the per capita gross domestic product in China in 2023) per QALY. Parameters in the York model were captured from network meta-analyses and literature including treatment response, short-term disease progression, patient functioning and long-term structural disease progression. Utilities are dependent on indicators such as the BASDAI score, the BASFI score, gender and age. Drug prices were analysed using the median price of the Chinese market from YAOZH net in the basic analysis. Costs and outcomes were discounted at 5.0%. We performed deterministic and probabilistic sensitivity analyses to investigate the robustness of the results. The prices of original drugs and generic drugs were used in the scenario analysis. RESULTS: Compared with CC, the ICER of golimumab was ¥104,217.4/QALY, which is between 1 and 3 times the GDP per capita, while the ICERs of the other six targeted therapies were less than ¥89,358/QALY. The specific economic rank of the targeted therapy was as follows: secukinumab > ixekizumab > tofacitinib > infliximab > etanercept > adalimumab > golimumab. Treatment response rates such as the BASDAI50, changes in the BASDAI/BASFI scores and the discounting rate were key model drivers. According to the scenario analysis, IL-17 inhibitors were still the most economical intervention when original drugs and generic drugs were used. CONCLUSION: Targeted therapies are cost-effective treatments for AS. Overall, IL-17 inhibitors were the dominant treatment. The choice of the brand-new prices or generic drug prices can greatly affect economics.

Elucidating the causal nexus between antibody-mediated immunity and autoimmune diseases: Insights from bidirectional mendelian randomization, gene expression profiling, and drug sensitivity analysis.

OBJECTIVE: This study aimed to elucidate the causal relationships between antibodies and autoimmune diseases using Mendelian randomization (MR). METHODS: Data on 46 antibodies were obtained from genome-wide association studies (GWAS). Autoimmune disease data were sourced from the FinnGen consortium and the IEU OpenGWAS project. Inverse-variance weighted (IVW) analysis was the primary method, supplemented by heterogeneity and sensitivity analyses. We also examined gene expression near significant SNPs and conducted drug sensitivity analyses. RESULTS: Antibodies and autoimmune diseases exhibit diverse interactions. Antibodies produced after Polyomavirus infection tend to increase the risk of several autoimmune diseases, while those following Human herpesvirus 6 infection generally reduce it. The impact of Helicobacter pylori infection varies, with different antibodies affecting autoimmune diseases in distinct ways. Overall, antibodies significantly influence the risk of developing autoimmune diseases, whereas autoimmune diseases have a lesser impact on antibody levels. Gene expression and drug sensitivity analyses identified multiple genes and drugs as potential treatment options for ankylosing spondylitis (AS), with the AIF1 gene being particularly promising. CONCLUSIONS: Bidirectional MR analysis confirms complex causal relationships between various antibodies and autoimmune diseases, revealing intricate patterns of post-infection antibody interactions. Several drugs and genes, notably AIF1, show potential as candidates for AS treatment, offering new avenues for research. Further exploration of the underlying mechanisms is necessary.

Opioid Use and Healthcare Utilization in Adults With Psoriatic Arthritis and Ankylosing Spondylitis.

OBJECTIVE: Opioid use among individuals with spondyloarthritis is common; however, data on whether these individuals have higher utilization of the healthcare system are lacking. We examined the association between opioid use and healthcare utilization and costs among patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). METHODS: We included adults with PsA or AS enrolled in the FORWARD registry, with ≥ 1 completed disease activity or disability questionnaire between 2010 and 2019. The exposure was patient-reported opioid use, and the outcomes were annualized healthcare utilization and prescription costs. We used negative binomial regression to assess the association between opioid use and the utilization outcomes, and generalized linear models with γ-distribution and log link function for the association between opioid use and costs. Models were adjusted for age, sex, and hospitalization. AS and PsA were studied separately. RESULTS: Among 828 patients with PsA, 21.4% used opioids; for those with AS, 27.2% of 334 patients reported opioid use. Opioid users had higher healthcare utilization and costs, including increased medical visits, diagnostic tests, direct medical costs, and pharmacy expenses. Opioid users had 32-33% more medical visits annually vs nonusers. Patients using opioids spent more on medical visits annually compared to nonusers (US $3464 vs $2706 for PsA; US $4500 vs $3660 for AS). CONCLUSION: Compared to patients not using opioids, patients with PsA and AS who used opioids had higher healthcare utilization and higher health-related costs. New care pathways are needed to improve care and reduce costs.

[Role of intercellular adhesion molecule-1 in adhesion and migration of mesenchymal stem cells in ankylosing spondylitis and its mechanisms].

Objective: To investigate the role and underlying mechanisms of intercellular adhesion molecule-1 (ICAM-1) in the adhesion and migration of mesenchymal stem cells (MSCs) in patients with ankylosing spondylitis (AS). Methods: Bone marrow and ligament tissues were collected during surgery from patients with AS and thoracolumbar fractures (as controls, HC) treated from October 2021 to October 2022 at Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital. MSCs were isolated and cultured from the bone marrow using the Ficoll separation method. Cell morphology was observed under high-resolution microscopy, and differences in the cytoskeletal features between AS-and HC-MSCs were analyzed through immunofluorescence staining. The expression of ICAM-1 was quantified in both groups using real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. Transwell migration assays and wound healing experiments were conducted to evaluate the differences in migration rates between the two groups of MSCs. Results: The interspinous ligament and bone marrow was acquired in AS (2 males and 1 female; 33, 37, 32 years old, respectively) and no-AS patients (2 males and 1 female; 35, 32, 38 years old, respectively). AS-MSCs exhibited broader cell morphology compared to HC-MSCs under bright field and fluorescence microscopy. Immunofluorescence staining of the interspinous ligament showed higher expression of ICAM-1 (68.38±3.42 vs 48.31±2.43) and CD105 (37.97±2.16 vs 23.36±2.06) in AS patients (both P<0.001). Western blot and RT-qPCR analysis revealed significantly stronger protein expression and transcription levels of ICAM-1 in AS-MSCs when compared to those in HC-MSCs (both P<0.001). Flow cytometry confirmed greater mean fluorescence intensity of ICAM-1 in AS-MSCs than in that in HC-MSCs (924.30±54.99 vs 636.47±40.03, P=0.002). Regarding cell adhesion efficiency, it showed no significant difference between AS-MSCs and HC-MSCs in the early stage of adhesion (0.5 h: 1 496±213 vs 1 205±163, P=0.133), but they were all significantly higher in AS-MSCs in the later stage (1 h: 2 894±172 vs 1 908±155, P=0.002; 2 h: 4 540±286 vs 3 334±188, P=0.004; 3 h: 5 212±281 vs 4 208±303, P=0.014). Finally, cell migration experiments demonstrated a stronger migration capability of AS-MSCs compared to HC-MSCs (5 449±172 vs 4 016±155, P<0.001), and the inhibition efficiency of A-205804 on the migration rate of AS-MSCs was stronger than that on HC-MSCs (2 145±239 vs 3 539±316, P=0.004). Conclusions: The aberrant expression of ICAM-1 markedly influences the adhesion and migration dynamics of MSCs. Elevated ICAM-1 levels in MSCs derives from patients with AS significantly enhance their migratory capabilities.

Identification of necroptosis-related genes in ankylosing spondylitis by bioinformatics and experimental validation.

The pathogenesis of ankylosing spondylitis (AS) remains unclear, and while recent studies have implicated necroptosis in various autoimmune diseases, an investigation of its relationship with AS has not been reported. In this study, we utilized the Gene Expression Omnibus database to compare gene expressions between AS patients and healthy controls, identifying 18 differentially expressed necroptosis-related genes (DENRGs), with 8 upregulated and 10 downregulated. Through the application of three machine learning algorithms-least absolute shrinkage and selection operation, support vector machine-recursive feature elimination and random forest-two hub genes, FASLG and TARDBP, were pinpointed. These genes demonstrated high specificity and sensitivity for AS diagnosis, as evidenced by receiver operating characteristic curve analysis. These findings were further supported by external datasets and cellular experiments, which confirmed the downregulation of FASLG and upregulation of TARDBP in AS patients. Immune cell infiltration analysis suggested that CD4+ T cells, CD8+ T cells, NK cells and neutrophils may be associated with the development of AS. Notably, in the group with high FASLG expression, there was a significant infiltration of CD8+ T cells, memory-activated CD4+ T cells and resting NK cells, with relatively less infiltration of memory-resting CD4+ T cells and neutrophils. Conversely, in the group with high TARDBP expression, there was enhanced infiltration of naïve CD4+ T cells and M0 macrophages, with a reduced presence of memory-resting CD4+ T cells. In summary, FASLG and TARDBP may contribute to AS pathogenesis by regulating the immune microenvironment and immune-related signalling pathways. These findings offer new insights into the molecular mechanisms of AS and suggest potential new targets for therapeutic strategies.

Detecting Amyloid Goiter With 99mTc-PYP SPECT/CT in the Setting of Ankylosing Spondylitis: An Uncommon Involvement of AA Amyloidosis.

ABSTRACT: We present a case with systemic amyloidosis secondary to ankylosing spondylitis (AA amyloidosis), whose 99mTc PYP scintigraphy revealed amyloid deposition in the thyroid gland (amyloid goiter). Amyloidosis is characterized by extracellular accumulation of amyloid fibril proteins leading to organ malfunction. Even though AA amyloidosis can be observed in patients with systemic inflammatory diseases, it is a very rare complication in ankylosing spondylitis. SPECT/CT images showed diffuse tracer uptake in enlarged thyroid gland containing fat density areas.

Clinical performance of the ASAS health index in chinese patients with ankylosing spondylitis and its influencing factors.

OBJECTIVE: The aim of this study was to investigate the status of health-related quality of life in Chinese patients with ankylosing spondylitis (AS) and to analyze factors associated with the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) in AS and its relationship with disease activity and psychological status. METHODS: A cross-sectional study of 484 patients with AS attending 10 hospitals in China from March 2021 to September 2023 was recruited. The ASAS-HI assessed general health and functional status; the Depression Anxiety Stress Scales (DASS-21) assessed psychological disorders such as anxiety, depression, and stress; and the Functional Assessment of Chronic illness Therapy-Fatigue Scale (FACIT-F) assessed patients' fatigue symptoms; the Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Measurement Index (BASMI) were used to assess patients' disease activity and functional impairment. The correlation between ASAS-HI and the ASDAS, poor psychological status, and fatigue symptoms was observed. Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of ASAS-HI. RESULTS: A total of 484 patients were included in this study of whom 162 were in poor health, 139 in moderate health, and 183 in good health. On univariate analysis, disease activity is an important factor affecting ASAS-HI. People with extremely high disease activity (ASDAS ≥ 3.5) had a 12 times elevated risk of having poor health status (OR = 12.53; P < 0.001). Other significant covariates included age ≥ 36 (OR = 1.58; P = 0.015), BMI ≥ 24 kg/m2 (OR = 2.93; P = 0.013), smoke (OR = 1.96; P = 0.002), BASFI (OR = 1.49; P < 0.001), BASMI (OR = 1.22; P < 0.001), fatigue (OR = 6.28; P < 0.001), and bad psychological conditions such as depression (OR = 10.86; P < 0.001), anxiety (OR = 3.88; P < 0.001), and stress (OR = 4.65; P < 0.001). The use of bMARDs is inversely associated with the appearance of adverse health status (OR = 0.54; P = 0.012). There was no significant relationship between HLA-B27 and sex. Multivariable logistic regression showed that higher disease activity (ASDAS ≥ 3.5) (OR = 5.14; P = 0.005), higher scores of BASMI (OR = 1.10; P = 0.009), self-reported depression (OR = 3.68; P = 0.007), and fatigue (OR = 2.76; P < 0.001) were factors associated with adverse health status. CONCLUSION: The health status of AS patients is related to age, BMI, smoking, disease activity, poor psychological status, and fatigue and is influenced by a combination of multiple factors such as emotional state, economic level, pain, and dysfunction. Therefore, clinicians should pay attention to the early assessment of ASAS-HI in order to improve the prognosis of the disease. Key Points •Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease with a long course and heavy disease burden, which greatly affects patients' quality of life. Therefore, this study aims to evaluate the health status of ankylosing spondylitis in the Chinese population and its influencing factors. •This is a multi-center cross-sectional study in China, which can better reflect the overall situation of the Chinese population.

[Effects of Zhoutian moxibustion on pain symptoms and inflammatory factors in patients with ankylosing spondylitis of cold-damp obstruction].

OBJECTIVE: To observe the effects of Zhoutian moxibustion on pain symptoms and serum inflammatory factors in patients with ankylosing spondylitis of cold-damp obstruction. METHODS: Eighty-four patients with ankylosing spondylitis of cold-damp obstruction were randomly divided into a Zhoutian moxibustion group (42 cases, 2 cases dropped out) and a governor vessel moxibustion group (42 cases, 2 cases dropped out, 1 case discontinued). Both groups were given oral administration of sulfasalazine enteric-coated tablets as basic treatment. The governor vessel moxibustion group was treated with moxibustion box from Dazhui (GV 14) to Yaoyangguan (GV 3), one hour per treatment; the Zhoutian moxibustion group was treated with moxibustion box from Tiantu (CV 22) to Zhongji (CV 3) in addition to the governor vessel moxibustion group, two hours per treatment. Both groups were treated once every 3 days, twice a week, for a total of 9 weeks. The pain symptom scores of the two groups were observed before treatment and at the 3rd, 6th, and 9th weeks into treatment. ELISA was used to detect the levels of serum interleukin (IL)-1ß, IL-18, and tumor necrosis factor-α (TNF-α) before and after treatment, and the clinical efficacy of the two groups was evaluated after treatment. RESULTS: Except for the joint pain scores at the 3rd week into treatment, the total scores and the each sub-item score of pain symptom in the two groups were lower than those before treatment at the 3rd, 6th, and 9th weeks into treatment (P<0.05); at the 3rd, 6th, and 9th weeks into treatment, the total scores of pain symptom and the scores of lumbar sacral pain, back pain, joint cold pain, and limited mobility in the Zhoutian moxibustion group were lower than those in the governor vessel moxibustion group (P<0.05). After treatment, the levels of serum IL-1ß, IL-18 and TNF-α in both groups were lower than those before treatment (P<0.05), and the levels of serum IL-1ß, IL-18, and TNF-α in the Zhoutian moxibustion group were lower than those in the governor vessel moxibustion group (P<0.05). The total effective rate was 90.0% (36/40) in the Zhoutian moxibustion group, which was higher than 76.9% (30/39) in the governor vessel moxibustion group (P<0.05). CONCLUSION: Zhoutian moxibustion could effectively improve various pain symptoms in patients with ankylosing spondylitis of cold-damp obstruction, and reduce the expression of inflammatory factors.

Detection Ewingella americana from a patient with Andersson lesion in ankylosing spondylitis by metagenomic next-generation sequencing test: a case report.

BACKGROUND: Andersen's lesion (AL) is a rare complication of ankylosing spondylitis (AS), characterized by nonneoplastic bone destruction, typically manifested as bone destruction and sclerosis in the vertebral body and/or intervertebral disc area. At present, there is no consensus on the pathology and etiology of AL. Repeated trauma, inflammation in essence and part of the natural history of Ankylosing spondylitis itself are the most widely recognized theories of the etiology of AL. However, positive bacteria cultured in bone biopsy of Andersen's lesion (AL) in Ankylosing spondylitis patients are extremely rare. Herein, we report a rare case of detecting Ewingella americana from a patient with Andersson lesion in ankylosing spondylitis by Metagenomic Next-Generation Sequencing (mNGS) Test. CASE PRESENTATION: This case involved a 39-year-old male with a history of AS for 11 years, who developed AL (T11/12) in the thoracic vertebrae. After sufficient preoperative preparation, we successfully performed one-stage posterior approach corrective surgery and collected bone biopsies samples for examination. Cultured bacteria were not found, and pathological histology indicated infiltration of inflammatory cells. However, it is worth noting that we discovered a gram-negative bacterium, the Ewingella americana, through mNGS testing. Further histopathological examination suggests chronic inflammatory cell infiltration. After one-stage posterior approach corrective surgery, the patient's condition significantly improved. At the 6-month follow-up, the pain significantly decreased, and the patient returned to normal life. CONCLUSION: We detected Ewinia americana in the bone biopsies of Andersson lesion (AL) in ankylosing spondylitis patient by mNGS.