Rheumatology and immunology research最新文献

Background and objectives: The latest prevalence data for rheumatoid arthritis (RA) is essential for effective disease control and management. Although numerous studies examine the global burden of RA, recent data specific to China has been lacking. The aim of this study is to evaluate the variations of RA burden in mainland China from 1990 to 2021 utilizing data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) study 2021.

Methods: We conducted a retrospective analysis of RA burden in China based on the GBD 2021 study. We collected data on RA prevalence, incidence, and disability adjusted life years in China from 1990 to 2021, then calculated the estimated annual percentage change (EAPC) to summarize the overall trends.

Results: In 2021, the total numbers of prevalent cases, incident cases, and disability-adjusted life years (DALYs) for RA in China were 4,755,500, 247,300, and 833,800, respectively; From 1990 to 2021, the rates of incidence, prevalence, and DALYs of RA showed an increasing trend, with EAPCs of 0.61, 0.59, and 0.17, respectively. Throughout this period, the RA burden was notably higher in females than in males. In 2021, RA incidence rates among individuals aged 15-44, 45-59, and 60-85+ followed an approximate 1∶1∶1 ratio. Projections using the Bayesian Age-Period-Cohort (BAPC) model indicated that by 2045, compared to 2021, the total incident cases, prevalent cases, and DALYs of RA in China are expected to increase by 15.7%, 13.2%, and 4.2%, respectively.

Conclusion: Over the past 32 years, the RA burden in China had continued to increase, and is expected to rise substantially over the next decade. Therefore, it is necessary to strengthen the prevention and management of RA, with priority given to the female population and young patients.

Background and objectives: No prior studies have directly compared sirolimus with the standard of care (SoC) for lupus nephritis (LN) patients. This study aimed to compare the efficacy and safety of sirolimus with mycophenolate mofetil (MMF) for the treatment of LN.

Methods: A real-world cohort study based on the Chinese SLE Treatment and Research (CSTAR) registry was conducted. Patients with active LN who were prescribed either sirolimus or MMF were enrolled. Propensity score matching was applied to ensure comparable baseline disease conditions. SLE disease activity indices, serological parameters, steroid doses, renal efficacy, and adverse events were evaluated at 3-month, 6-month, and 12-month follow-ups.

Results: Data from 53 patients in each group were analyzed. Sirolimus demonstrated clinical effectiveness comparable to MMF, as evidenced by similar rates of lupus nephritis remission and lupus low disease activity state (LLDAS) /remission or a clinical response (reduction of SLE Disease Activity Index 2000 [SLEDAI-2K] ≥4 and increase in physician's global assessment [PhGA] < 0.3), as well as changes in 24-hour urine protein level, SLEDAI-2K score, PhGA score, and steroid tapering effect (P ≥ 0.05 at all follow-up timepoints). Notably, sirolimus group exhibited greater improvements in complement levels compared to MMF group at 3, 6, and 12 months. Ten adverse events in sirolimus group and one in MMF group were reported, with no severe adverse events.

Conclusion: Sirolimus demonstrated comparable efficacy to MMF in the treatment of LN and glucocorticoid tapering, with additional benefits in serological improvement. Furthermore, sirolimus was well tolerated in LN patients, supporting its potential as a therapeutic option for LN.

Background and objectives: Biologic therapy has been used for Behçet's Syndrome after first-line immunomodulation, but in the absence of high-quality evidence or predictive biomarkers. BIO-BEHÇET'S was a randomized controlled clinical trial to compare the two most widely used biologics for Behçet's Syndrome at that time, infliximab versus interferon-α2a, and identify potential biomarkers for response.

Methods: A total of 79 patients with active Behçet's Syndrome were randomized to either infliximab (REMICADE) or interferon-α2a (ROFERON) according to the UK national treatment pathway, and follow-up with symptom-directed examination undertaken at Weeks 12 and 24. The head-to-head trial included an exploratory analysis on the potential role of single nucleotide polymorphisms (SNPs) and urinary metabolomic to act as biomarkers for drug response. Genotypic analysis was performed to determine whether four SNPs in IFNL3 and IFNL4 - selected based on known effects - impacted primary and secondary outcomes. For metabolomic analyses, urine samples were analyzed by nuclear magnetic resonance spectroscopy and principal component analysis.

Results: Genetic data suggested potential association between outcomes and carriage of rs4803221 or rs7248668 variants in the IFNL3 (IL-28B) gene locus for interferon-α2a patients; however, with the relatively small sample, statistical significance was lost when corrected for multiple testing. Metabolomic analysis identified potential markers of metabolic response to infliximab.

Conclusion: BIO-BEHÇET'S suggests there is potential for a novel metabolomic biomarker that can identify response to infliximab in patients with Behçet's Syndrome. Further work will characterize the appropriate metabolite (s) from existing samples to inform future prospective trials to study this in more detail clinically.

Background and objective: Multiple studies have shown a substantial association between obstructive sleep apnea (OSA) and rheumatic disease. However, traditional studies are susceptible to confounding factors or reverse causal relationships, and the exact causal relationship still needs to be clearly defined. This study aims to use a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal association between OSA and rheumatoid immune diseases.

Methods: We conducted a two-sample bidirectional MR analysis by using large-scale genome-wide association studies (GWAS) summary statistics to investigate whether there is a causal relationship between OSA and rheumatic disease. Inverse variance weighted (IVW) was used as the primary analysis approach, supplemented by MR-Egger and Weighted median methods. Sensitivity analyses were conducted to ensure the robustness of the results.

Results: The MR predicted ankylosing spondylitis (AS) was associated with risk of OSA (IVW: OR = 1.0239, 95% CI = 1.0086 to 1.0394, P = 0.0021; MR-Egger: OR = 1.0374, 95% CI = 1.0089 to 1.0668, P = 0.0326; weighted median: OR = 1.0287, 95% CI = 1.0109 to 1.0467, P = 0.0014). However, no bidirectional causal association was found between other rheumatic disease and OSA. The sensitivity analysis confirmed the robustness of the results.

Conclusions: Our analysis suggests a potential causal relationship between AS and OSA. There was no direct causal relationship between OSA and other rheumatic disease. We need more experimental research on specific pathological and physiological mechanisms in the future.

Background and objectives: Raynaud's phenomenon (RP) and digital ulcers (DUs) impact the quality of life (QoL) of systemic sclerosis (SSc) patients. Calcium channel blockers (CCBs) and phosphodiesterase-5 inhibitors (PDE-5i) have been used to improve blood flow. However, vasodilators are limited in patients with low blood pressure. We aimed to determine the eficacy and safety of 2% isosorbide dinitrate (ISDN) cream as an adjunctive for treating DUs and RP.

Methods: A cohort study was conducted at the Scleroderma Clinic at Khon Kaen University's Srinagarind Hospital in Khon Kaen, Thailand between January 2021 and December 2022. The study included adult SSc patients, who had received 2% ISDN cream for treatment of DUs or RP as adjuvant and with/or without receiving CCBs and/or PDE-5i as a background treatment for DUs and RP. Patients had to have follow-up data between 2 and 4 months after starting treatment. The median treatment duration was 2.8 months. Dosages of sustained-release nifedipine ranged from 10-80 mg and sildenafil ranged from 12.5-150 mg. Topical 2% ISDN cream was thinly applied three times a day. The treatment responses of DUs (ulcer size and pain) and RP (frequency and duration of attack) were according to patients' self-assessment, categorized into 3 levels Improvement Stable and Worsening. Before and after the treatment period of 2% ISDN cream the Quality of life was evaluated by using the EuroQoL five dimensions (EQ-5D) assessment by attending physicians.

Results: In terms of anxiety, QoL, as evaluated by the EQ-5D, significantly improved after treatment with 2% ISDN cream in patients with DUs compared to before treatment. When used as an adjunct to CCB, 2% ISDN cream resulted in stability or improvement of RP in 43.2% of patients, DUs in 41.4% of patients, and both RP and DUs in 41.0% of patients. When used as an adjunct to PDE-5i as background therapy, it resulted in stability or improvement of RP in 13.5% of patients, DUs in 13.8% of patients, and both RP and DUs in 15.4% of patients.

Conclusions: Topical 2% ISDN cream may help to reduce anxiety when DUs were improved and improve overall QoL.

Background: Joint deformities in juvenile idiopathic arthritis (JIA) are most common in children, are not defined in term of angular measurements. The study was aimed to evaluate the joint deformities in angular deviation of the afected joints in JIA patients.

Methods: This cross-sectional study was conducted at Pediatric Rheumatology Clinic, North Bengal Medical College, West Bengal. The children aged 2-16 years diagnosed with JIA according to the International League of Associations for Rheumatology (ILAR) criteria were included in the study. Patients with co-morbid disease, hemodynamic instability, and other acute conditions were excluded. Angular measurements were performed using goniometer.

Results: The mean age of children was (8.05 ± 3.20) years of which 57.5% was male and the disease duration associated with the deformities in JIA. The prevalent subtypes of JIA were Oligoarticular JIA (oligoJIA)(40%), followed by polyarticular JIA (pJIA) (35%) and systemic-onset JIA (sJIA) (12.5%). The commonly involved joint were knee (40%), followed by small joint of hand (32.5%), ankle (30%), wrist and foot (17.5% each), elbow (12.5%) and cervical joint (7.5%). In pJIA, duration of disease significantly (P = 0.017) associated with the number of affected joints. Mostly, wrist, knee and ankle deformities were observed in oligoJIA, pJIA and sJIA. The angular deviation (mean ± SD) of right and left knee were (2° ± 4.16°) and (1.87° ± 5.12°) in oligoJIA, (13.36° ± 17.03°) and (12.5° ± 15.08°) in pJIA and (3° ± 6.71°) and (2.4° ± 5.37°) in sJIA. Right ankle angular deviation were (2.62° ± 5.06), (5.43° ± 8.21°) and 4° ± 8.94° respectively in oligoJIA, pJIA and sJIA. The angular deviation of right and left wrist were (1.25° ± 3.41°) and (0.94° ± 3.75°) in oligoJIA, (4.07° ± 8.93°) and (4.14° ± 9.36°) in pJIA and (2.45° ± 5.37°) and (2° ± 4.47°) in sJIA.

Conclusion: This study is the first study from India to quantify the angular deviation of deformed joints in JIA. Angular deviation could serve as a valuable parameter for monitoring disease progression across various JIA subtypes.

Background: Circular RNAs (circRNAs) play a crucial role in the development of various diseases. However, few studies have investigated the role of circRNAs in rheumatoid arthritis (RA). Herein, we aimed to identified the novel circRNAs involved in the migration and invasion of RA fibroblast-like synoviocytes (RA-FLS).

Methods: The RA-FLS were isolated from the synovial membrane of patients with RA. The CircRNA profile was screened by CircRNA microarray analysis. Circ_0088200 and miR-127-5p expression levels were detected using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The protein level of matrix metalloproteinase 1 (MMP1) was evaluated by western blotting. Wound healing and Transwell assays were performed to analyze the migration and invasion of RA-FLS. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were used to validate the interaction between Circ_0088200 and miR-127-5p. Collagen-induced arthritis (CIA) mouse models were established to evaluate the role of Circ_0088200 in the development of arthritis in vivo.

Results: Circ_0088200 was highly expressed in RA-FLS compared with osteoarthritis fibroblast-like synoviocytes (OAFLS) and correlated positively with the disease activity score in 28 joints. Inhibition of Circ_0088200 suppressed the migration and invasion of RA-FLS. Conversely, overexpression of Circ_0088200 significant promoted the migration and invasion of RA-FLS. Mechanistically, Circ_0088200 functions as a sponge for miR-127-5p and relieve its repressive effect on MMP1, thereby promoting the migration and invasion of RA-FLS. Importantly, intra-articular injection of Adenoassociated virus expressing Circ_0088200 significantly increased the severity of arthritis in mice with CIA.

Conclusion: Circ_0088200 promotes the migration and invasion of RA-FLS by sponging miR-127-5p. Thus Circ_0088200 is a potential therapeutic target for RA.