Inside the Joint of Inflammatory Arthritis Patients: Handling and Processing of Synovial Tissue Biopsies for High Throughput Analysis.

Inflammatory arthritis is a chronic systemic autoimmune disease of unknown etiology, which affects the joints. If untreated, these diseases can have a detrimental effect on the patient's quality of life, leading to disabilities, and therefore, exhibit a significant socioeconomic impact and burden. While studies of immune cell populations in arthritis patient's peripheral blood have been informative regarding potential immune cell dysfunction and possible patient stratification, there are considerable limitations in identifying the early events that lead to synovial inflammation. The joint, as the site of inflammation and the local microenvironment, exhibit unique characteristics that contribute to disease pathogenesis. Understanding the contribution of immune and stromal cell interactions within the inflamed joint has been met with several technical challenges. Additionally, the limited availability of synovial tissue biopsies is a key incentive for the utilization of high-throughput techniques in order to maximize information gain. This review aims to provide an overview of key methods and novel techniques that are used in the handling, processing and analysis of synovial tissue biopsies and the potential synergy between these techniques. Herein, we describe the utilization of high dimensionality flow cytometric analysis, single cell RNA sequencing, ex vivo functional assays and non-intrusive metabolic characterization of synovial cells on a single cell level based on fluorescent lifetime imaging microscopy. Additionally, we recommend important points of consideration regarding the effect of different storage and handling techniques on downstream analysis of synovial tissue samples. The introduction of new powerful techniques in the study of synovial tissue inflammation, brings new challenges but importantly, significant opportunities. Implementation of novel approaches will accelerate our path toward understanding of the mechanisms involved in the pathogenesis of inflammatory arthritis and lead to the identification of new avenues of therapeutic intervention.

Exploring the effect of alcohol on disease activity and outcomes in rheumatoid arthritis through systematic review and meta-analysis.

To evaluate the effects of alcohol consumption on disease activity in rheumatoid arthritis. EMBASE, Pubmed, the Cochrane Library, and Web of Science were searched until July 29, 2020. English language studies that reported disease activity outcomes in rheumatoid arthritis were included. Studies were excluded if they were reviews, case reports, had fewer than 20 patients, or reported on prevalence but not disease activity in RA. Forest plots were used to determine pooled mean difference and were generated on RevMan5.3. Linear regression was used to determine correlations between alcohol and antibody status, gender, and smoking status. The search identified 4126 citations of which 14 were included. The pooled mean difference in DAS28 (95% CI) was 0.34 (0.24, 0.44) (p < 10-5) between drinkers and non-drinkers with lower DAS28 in non-drinkers, 0.33 (0.05, 0.62) (p = 0.02) between heavy drinkers and non-drinkers with lower DAS28 in heavy drinkers, and 0.00 (- 0.30, 0.30) (p = 0.98) between low- and high-risk drinkers. The mean difference of HAQ assessments was significantly different between those who drink alcohol compared to those who do not, with drinkers reporting lower HAQ scores (0.3 (0.18, 0.41), p < 10-5). There was no significant correlation between drinking and gender, smoking status, or antibody positivity. Alcohol consumption is associated with lower disease activity and self-reported health assessment in rheumatoid arthritis. However, drinking has no correlation with smoking, gender, or antibody status.

The effects of alcohol consumption and its associations with disease activity among 979 patients with inflammatory arthritis.

OBJECTIVE: The role of alcohol in inflammatory disease remains debated. This study explores the relationship between alcohol and disease activity in patients with inflammatory arthritis. METHODS: Patients attending a rheumatology clinic between 2010 and 2020 were prospectively followed. Information on demographics, alcohol use, smoking habits and disease outcome measures were collected from these patients. Statistical analysis included univariate and multivariate linear and binary logistic regressions, Mann-Whitney U tests and one-way analysis of variance with Tukey's honest significant difference (HSD) test. RESULTS: Of the 979 analysed patients, 62% had rheumatoid arthritis (RA), 26.7% had psoriatic arthritis (PsA) and 11.2% had ankylosing spondylitis. Mean DAS28-CRP (Disease Activity Score 28 - C-reactive protein) in RA and PsA at 1 year was 2.96±1.39, and 64.2% of patients were in remission (DAS28-CRP ≤2.6 or BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) ≤4). Both male gender and risky drinking (>15 units of weekly alcohol) were significantly associated with remission. Compared with women, men had an OR of 1.8 (1.1, 2.5) (p=0.034) for any alcohol consumption and 6.9 (4.7, 9.1) (p=0.001) for drinking at least 15 weekly drinks. When adjusted for gender, there was no association between alcohol and disease activity. Yet, when adjusted for alcohol consumption, gender still significantly influenced disease activity. CONCLUSION: While it may appear that alcohol is linked to remission in inflammatory arthritis, when adjusted for gender, it is not. Men with inflammatory arthritis drink significantly more than women and have less severe disease activity.

Evaluating Posterior Cruciate Ligament Integrity in Inflammatory Arthritis Patients Prescribed Biologic Agents: A Radiological Case-Control Study.

Introduction Patients with inflammatory arthropathies present a significant challenge to the arthroplasty surgeon when they present with symptomatic degenerative changes of their knee joint. Debate is ongoing regarding the selection of implants for this cohort of patients. There is conflicting evidence for the use of posterior-stabilising (PS) over cruciate-retaining (CR) designs in this cohort. Biologics are licensed for use in moderate-to-severe disease that has not responded to conventional treatment. To our knowledge, there are no studies that have assessed the integrity of the posterior cruciate ligament (PCL) on magnetic resonance imaging (MRI) in these patients with more advanced disease prescribed biologic agents. Aim The aim of this study is to assess the integrity of the PCL on MRI in patients with inflammatory arthritis who are prescribed biologic agents. Methods A case-control study was performed, with cases identified through chart review to confirm prescription of biologic agents for inflammatory arthropathies, who also had contemporaneous MRI knee scans performed. Knee MRIs for age- and sex-matched controls with osteoarthritis (OA) and meniscal pathology were identified from the National Joint Registry and the Hospital In-Patient Enquiry (HIPE), respectively. The MRIs were reviewed by two musculoskeletal radiologists who were blinded to the clinical details. They were asked to assess the MRIs to determine PCL integrity, synovial Inflammation, and any associated pathology. Results No difference was noted in the rate of synovitis, PCL attenuation, or PCL tears between the OA and inflammatory arthropathy groups (p > 0.05). Conclusions The results of this study show no difference in the integrity and continuity of the PCL in those patients for age- and sex-matched controls on MRI. This finding lends support to the use of CR total knee arthroplasty in patients with inflammatory arthropathy on biologic agents.