Inflammation In Rheumatoid Arthritis Research Articles

Epigenetic targets of Janus kinase inhibitors are linked to genetic risks of rheumatoid arthritis

BackgroundCurrent strategies that target cytokines (e.g., tumor necrosis factor (TNF)-α), or signaling molecules (e.g., Janus kinase (JAK)) have advanced the management for allergies and autoimmune diseases. Nevertheless, the molecular mechanism that underpins its clinical efficacy have largely remained elusive, especially in the local tissue environment. Here, we aimed to identify the genetic, epigenetic, and immunological targets of JAK inhibitors (JAKis), focusing on their effects on synovial fibroblasts (SFs), the major local effectors associated with destructive joint inflammation in rheumatoid arthritis (RA).MethodsSFs were activated by cytokines related to inflammation in RA, and were treated with three types of JAKis or a TNF-α inhibitor (TNFi). Dynamic changes in transcriptome and chromatin accessibility were profiled across samples to identify drug targets. Furthermore, the putative targets were validated using luciferase assays and clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. ResultsWe found that both JAKis and the TNFi targeted the inflammatory module including IL6. Conversely, specific gene signatures that were preferentially inhibited by either of the drug classes were identified. Strikingly, RA risk enhancers for CD40 and TRAF1 were distinctively regulated by JAKis and the TNFi. We performed luciferase assays and CRISPR-based genome editing, and successfully fine-mapped the single causal variants in these loci, rs6074022-CD40 and rs7021049-TRAF1.ConclusionsJAKis and the TNFi had a direct impact on different RA risk enhancers, and we identified nucleotide-resolution targets for both drugs. Distinctive targets of clinically effective drugs could be useful for tailoring the application of these drugs and future design of more efficient treatment strategies.

Risk for cardiovascular disease development in rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis have significant cardiovascular mortality and morbidity.ObjectiveTo investigate the effects of chronic inflammation in rheumatoid arthritis on cardiovascular morbidity association with cardiovascular risk factors risk factors. Mortality report is secondary just to show trends without sufficient statistical power as it is accidental endpoint.MethodsA total of 201 individuals without previous cardiovascular disease, 124 with rheumatoid arthritis (investigation group) and 77 with osteoarthritis (control group), were included in the study and followed up for an average of 8 years to assess the development of fatal or non-fatal cardiovascular diseases. The incidence and prevalence of cardiovascular risk factors were also investigated.ResultsThe total incidence of one or more fatal or nonfatal cardiovascular events was 43.9% in the investigation group and 37.5% in the control group. Of these patients, 31.7% and 30.9% survived cardiovascular events in the investigation and control groups, respectively. The most common cardiovascular disease among participants who completed the study and those who died during the study was chronic heart failure. The results of the subgroup analysis showed that strict inflammation control plays a central role in lowering cardiovascular risk.ConclusionA multidisciplinary approach to these patients is of paramount importance, especially with the cooperation of immunologists and cardiologists for early detection, prevention, and management of cardiovascular risks and diseases.

Impact of inflammation on cognitive function in patients with highly inflammatory rheumatoid arthritis

ObjectiveTo evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity.Patients and methodsWe performed a cross-sectional study of a cohort of patients with RA initiating their first biological...

The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis

Synovial tissue inflammation is a hallmark of rheumatoid arthritis (RA). Recent work has identified prominent pathogenic cell states in inflamed RA synovial tissue, such as T peripheral helper cells; however, the epigenetic regulation of these states has yet to be defined. Here, we examine genome-wide open chromatin at single-cell resolution in 30 synovial tissue samples, including 12 samples with transcriptional data in multimodal experiments. We identify 24 chromatin classes and predict their associated transcription factors, including a CD8 + GZMK+ class associated with EOMES and a lining fibroblast class associated with AP-1. By integrating with an RA tissue transcriptional atlas, we propose that these chromatin classes represent ‘superstates’ corresponding to multiple transcriptional cell states. Finally, we demonstrate the utility of this RA tissue chromatin atlas through the associations between disease phenotypes and chromatin class abundance, as well as the nomination of classes mediating the effects of putatively causal RA genetic variants.

Effect of Argentine tango sessions on total physical activity time in patients with chronic inflammatory rheumatism: randomized, controlled, pilot study.

The aim of this study was to evaluate the effect of an Argentine Tango (AT) program on total physical activity (PA) time in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). Prospective randomized controlled pilot study with two parallel groups. Participants were randomized 1:1 to attend a 24-week AT program from baseline to month6 for the immediate tango group (ITG) and a 12-week AT program from month3 to month6 for the wait-list control group (WLCG). Total PA time was measured at baseline, month3, and month6 using the Global Physical Activity Questionnaire-ONAPS and an accelerometer. Twenty-seven participants (15 RA and 12 SpA) were enrolled in the study. Thirteen participants in the WLCG and 14 in the ITG. At month3, there was no significant difference in the total PA time between the two groups. Longitudinal analyses revealed no significant difference between the two groups regarding PA, sedentary, fatigue, anxiety, depression, balance, physical performance, pain, and stress. However, body appreciation improved significantly in the ITG compared with the WLCG. Both groups showed improved physical abilities at 6month, including improvements in the 6-min walk test and timed up and go test. The ITG also reported reduced pain at months 3 and 6, while the WLCG exhibited improved balance at month 6. Although the AT program did not significantly increase total PA time in patients with CIR, it positively impacted body appreciation and physical abilities suggesting its potential as a complementary therapy. Key Points • Body appreciation significantly improved after a 24-week AT program, emphasizing the positive impact of dance on self-perception. • Both groups exhibited improved physical abilities at month 6, indicating a positive influence on participants' overall mobility and functional capacity. • The 24-week AT group reported reduced pain at months 3 and 6, and the 12-week AT group exhibited improved balance at month 6.

Macrophages-mediated delivery of protoporphyrin for sonodynamic therapy of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by infiltration of inflammatory cells, hyperplasia of synovium, and destruction of the joint cartilage. Owing to the low drug delivery efficiency and limited immunosuppression effect, complete cure for RA remains a formidable challenge. Here, we show that live macrophages (Mφs) carrying protoporphyrin-loaded Fe3O4 nanoparticles can migrate to the RA tissues and inhibit the inflammation by sonodynamic therapy. The inflammation of RA leads to the release of cytokines, which guides the migration of the Mφs into the RA tissues, realizing precise delivery of therapeutics. The following sonodynamic therapy induced by ultrasound and protoporphyrin destructs the proliferating synovial cells and also infiltrated inflammatory cells, demonstrating significant therapeutic effect for RA. Meanwhile, the cytokines and relapse of RA can be remarkably suppressed because of the efficient damage to the resident inflammatory cells.

Novel trifluoromethyl ketone derivatives as oral cPLA2/COX-2 dual inhibitors for resolution of inflammation in rheumatoid arthritis

Thirty-five trifluoromethyl hydrazones and seventeen trifluoromethyl oxime esters were designed and synthesized via molecular hybridization. All the target compounds were initially screened for in vitro anti-inflammatory activity by assessing their inhibitory effect on NO release in LPS-stimulated RAW264.7 cells, and the optimal compound was finally identified as 2-(3-Methoxyphenyl)-N'-((6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-ylidene)acetohydrazide (F26, IC50 = 4.55 ± 0.92 μM) with no cytotoxicity. Moreover, F26 potently reduced the production of PGE2 in LPS-stimulated RAW264.7 cells compared to indomethacin. The interaction of F26 with COX-2 and cPLA2 was directly verified by the CETSA technique. F26 was found to modulate the phosphorylation levels of p38 MAPK and NF-κB p65, as well as the protein expression of IκB, cPLA2, COX-2, and iNOS in LPS-stimulated rat peritoneal macrophages. Additionally, F26 was observed to prevent the nuclear translocation of NF-κB p65 in LPS-stimulated rat peritoneal macrophages by immunofluorescence localization. Therefore, the aforementioned in vitro experiments demonstrated that F26 blocked the p38 MAPK and NF-κB pathways by binding to COX-2 and cPLA2. In the adjuvant-induced arthritis model, F26 demonstrated a significant effect in preventing arthritis symptoms and inflammatory status in rats, exerting an immunomodulatory role by regulating the homeostasis between Th17 and Treg through inhibition of the p38 MAPK/cPLA2/COX-2/PGE2 and NF-κB pathways. Encouragingly, F26 caused less acute ulcerogenicity in rats at a dose of 50 mg/kg compared to indomethacin. Overall, F26 is a promising candidate worthy of further investigation for treating inflammation and associated pain with lesser gastrointestinal irritation, as well as other symptoms in which cPLA2 and COX-2 are implicated in the pathophysiology.

C-reactive protein is more suitable than Serum Amyloid A to monitor crises and attack-free periods in Systemic Auto-Inflammatory Diseases.

BackgroundWith their broad presentations and no global biomarker to discriminate crises and attack-free periods, Systemic Auto-Inflammatory Diseases (SAID) are difficult to manage. This study assessed Serum Amyloid A (SAA), C-reactive protein (CRP) and serum calprotectin as potential biomarkers to monitor patients with SAID. MethodSAA (already studied in Familial Mediterranean Fever (FMF)), CRP and serum calprotectin were measured on SAID adult patients from Juvenile Inflammatory Rheumatism (JIR) cohort during their follow-up visits between 2020 and 2022. Crises and attack-free periods were clinically determined. Results96 measures, mainly from FMF (43 %) and Unclassified SAID (USAID) (37 %) patients were included. Using ROC curves, a threshold with sensitivity and specificity of/over 75 % was determined for SAA (9 mg/L) and CRP (9 mg/L) but not for serum calprotectin, not investigated further. With this threshold, the results were similar in FMF and USAID patients’ subgroups. SAA and CRP showed a positive correlation with crises and attack-free periods in SAID patients (r = 0.4796, p < 0.001 and r = 0.5525, p < 0.001, respectively) as in FMF and USAID patients, with no significant difference between both markers in diagnosis value and ROC curves Area Under Curve (AUC) (p = 0.32). Only the CRP results were not influenced by obesity. ConclusionSAA and CRP can discriminate crisis and attack-free periods in our cohort of SAID patients mainly composed of FMF and USAID patients. However, only CRP can be used regardless of body mass index. It is the first report of common biomarkers for all SAID, including USAID patients, with CRP widely accessible in routine worldwide.

Plasma mtDNA as a possible contributor to and biomarker of inflammation in rheumatoid arthritis

ObjectivesNeutrophil extracellular trap formation and cell-free DNA (cfDNA) contribute to the inflammation in rheumatoid arthritis (RA), but it is unknown if mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) is more abundant in the circulation. It is unclear if DNA concentration measurements may assist in clinical decision-making.MethodsThis single-center prospective observational study collected plasma from consecutive RA patients and healthy blood donors. Platelets were removed, and mtDNA and nDNA copy numbers were quantified by polymerase chain reaction (PCR).ResultsOne hundred six RA patients and 85 healthy controls (HC) were recruited. Circulating median mtDNA copy numbers were increased 19.4-fold in the plasma of patients with RA (median 1.1 x108 copies/mL) compared to HC (median 5.4 x106 copies/mL, p<0.0001). Receiver operating characteristics (ROC) curve analysis of mtDNA copy numbers identified RA patients with high sensitivity (92.5%) and specificity (89.4%) with an area under the curve (AUC) of 0.97, p <0.0001 and a positive likelihood ratio of 8.7.Demographic, serological (rheumatoid factor (RF) positivity, anti-citrullinated protein antibodies (ACPA) positivity) and treatment factors were not associated with DNA concentrations. mtDNA plasma concentrations, however, correlated significantly with disease activity score-28- erythrocyte sedimentation rate (DAS28-ESR) and increased numerically with increasing DAS28-ESR and clinical disease activity index (CDAI) activity. MtDNA copy numbers also discriminated RA in remission (DAS28 <2.6) from HC (p<0.0001). Also, a correlation was observed between mtDNA and the ESR (p = 0.006, R= 0.29). Similar analyses showed no significance for nDNA.ConclusionIn contrast to nDNA, mtDNA is significantly elevated in the plasma of RA patients compared with HC. Regardless of RA activity, the abundance of circulating mtDNA is a sensitive discriminator between RA patients and HC. Further validation of the diagnostic value of mtDNA testing is required.

Subclinical joint inflammation in rheumatoid arthritis: comparing thermal and ultrasound imaging at the metacarpophalangeal joint

BackgroundWhile ultrasound and MRI are both superior to clinical examination in the detection of joint inflammation, there is presently a lack of data whether thermography may be similarly useful in the assessment of joint inflammation in patients with RA. Our study aims to evaluate the use of thermography in detecting subclinical joint inflammation at clinically quiescent (non-tender and non-swollen) metacarpophalangeal joints (MCPJs) in patients with rheumatoid arthritis (RA). The outcomes from thermography in our study will be compared with ultrasonography (which is a more established imaging tool used for joint inflammation assessment in RA).MethodsThe minimum (Tmin), average (Tavg) and maximum (Tmax) temperatures at the 10 MCPJs of each patient were summed to obtain the Total Tmin, Total Tavg and Total Tmax, respectively. Ultrasound grey-scale (GS) and power Doppler (PD) joint inflammation (scored semi-quantitatively, 0–3) at the 10 MCPJs were summed up to derive the respective TGS and TPD scores per patient. Pearson’s correlation and simple linear regression were respectively used to assess correlation and characterize relationships between thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TGS, TPD and the number of joint(s) with PD ≥ 1 or GS ≥ 2).ResultsIn this cross-sectional study, 420 clinically non-swollen and non-tender MCPJs from 42 RA patients were examined. All thermographic parameters (Total Tmin, Total Tavg and Total Tmax) correlated significantly (P-values ranging from 0.001 to 0.0012) with TGS score (correlation coefficient ranging from 0.421 to 0.430), TPD score (correlation coefficient ranging from 0.383 to 0.424), and the number of joint(s) with PD ≥ 1 or GS ≥ 2 (correlation coefficient ranging from 0.447 to 0.465). Similarly, simple linear regression demonstrated a statistically significant relationship (P-values ranging from 0.001 to 0.005) between all thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TPD and TGS).ConclusionFor the first time, thermographic temperatures were shown to correlate with ultrasound-detected joint inflammation at clinically quiescent MCPJs. The use of thermography in the detection of subclinical joint inflammation in RA appears promising and warrants further investigation.

Fibroblast expression of neurotransmitter receptor HTR2A associates with inflammation in rheumatoid arthritis joint

The study of neuroimmune crosstalk and the involvement of neurotransmitters in inflammation and bone health has illustrated their significance in joint-related conditions. One important mode of cell-to-cell communication in the synovial fluid (SF) is through extracellular vesicles (EVs) carrying microRNAs (miRNAs). The role of neurotransmitter receptors in the pathogenesis of inflammatory joint diseases, and whether there are specific miRNAs regulating differentially expressed HTR2A, contributing to the inflammatory processes and bone metabolism is unclear. Expression of neurotransmitter receptors and their correlated inflammatory molecules were identified in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium from a scRNA-seq dataset. Immunohistochemistry staining of synovial tissue (ST) from RA and OA patients was performed for validation. Expression of miRNAs targeting HTR2A carried by SF EVs was screened in low- and high-grade inflammation RA from a public dataset and validated by qPCR. HTR2A reduction by target miRNAs was verified by miRNAs mimics transfection into RA fibroblasts. HTR2A was found to be highly expressed in fibroblasts derived from RA synovial tissue. Its expression showed a positive correlation with the degree of inflammation observed. 5 miRNAs targeting HTR2A were decreased in RA SF EVs compared to OA, three of which, miR-214-3p, miR-3120-5p and miR-615-3p, mainly derived from monocytes in the SF, were validated as regulators of HTR2A expression. The findings suggest that fibroblast HTR2A may play a contributory role in inflammation and the pathogenesis of RA. Additionally, targeting miRNAs that act upon HTR2A could present novel therapeutic strategies for alleviating inflammation in RA.

E056 Particularities of the lipid profile in rheumatoid arthritis

Abstract Background/Aims Rheumatoid arthritis (RA), like all autoimmune diseases, is associated with a high cardiovascular risk. This risk is essentially linked to the chronic inflammation and dyslipidaemia engendered by this chronic inflammatory rheumatism. The objective of this work was to study the particularities of the lipid profile in RA. Methods We conducted a retrospective study including patients with RA according to ACR- EULAR 2010 criteria, followed in an internal medicine department between 2015 and 2022. Lipid profile data (total cholesterol (TC), high-density lipoproteins (HDLc), low-density lipoproteins (LDLc), and triglycerides (TG)) were collected. Results Eighty patients with RA were studied. The mean age was 60.79 years [range 30-91]. The sex ratio (F/H) was 4.33, with a clear female predominance. The mean age of disease onset was 46.34 years [extremes: 22-82]. A personal history of dyslipidaemia was noted in 19 patients: hypercholesterolemia, hypertriglyceridemia, and mixed dyslipidaemia were found in 8, 4 and 7 cases. Other comorbidities were arterial hypertension in 35% of cases (n = 28), diabetes in 30% of cases (n = 24), renal insufficiency in 6.25% of cases (n = 5) and a cardiovascular accident in 5% of cases (n = 4). Obesity was present in 15% of patients and smoking in 5%. 69 patients had a lipid panel. Dyslipidaemia was present in 66.7% of cases (n = 46). The mean TC level was 4.47 ± 1.0 mmol/L [range: 2.32 - 6.96 mmol/L], the mean TG level was 2.64 ± 0.81 [range: 0.90 - 4 mmol/L], the mean HDLc level was 1.106 ± 0.394 mmol/L [0.50 - 2] and the mean LDLc level was 1.38 ± 0.565 mmol/L [0.56 - 3.59 mmol/L]. Hypercholesterolemia (21.3%) and hypocholesterolaemia (21.3%) were the most common lipid abnormalities. Hypertriglyceridemia was observed in 10% of cases (n = 8). A low HDLc was observed in 20% of cases (n = 16). Only one patient had a high HDLc, with HDLc= 2 mmol/l. A low LDL was present in 10% of cases (n = 8). Conclusion In our study, hypolipidemia was the most common dyslipidaemia. This confirms the lipid paradox found in RA. Indeed, systemic inflammation is responsible for quantitative and qualitative alterations in lipoproteins. Stabilization of the disease leads to normalization of the lipid balance and improved control of cardiovascular risk. Disclosure I. Fenniche: None. M. Somai: None. I. Rachdi: None. I. Arbaoui: None. F. Daoud: None. S. Kochbati: None. B. Daoud: None. Z. Aydi: None. F. Boussema: None.

Macrophage-derived mir-100-5p orchestrates synovial proliferation and inflammation in rheumatoid arthritis through mTOR signaling

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation, causing substantial disability and reducing life quality. While macrophages are widely appreciated as a master regulator in the inflammatory response of RA, the precise mechanisms underlying the regulation of proliferation and inflammation in RA-derived fibroblast-like synoviocytes (RA-FLS) remain elusive. Here, we provide extensive evidence to demonstrate that macrophage contributes to RA microenvironment remodeling by extracellular vesicles (sEVs) and downstream miR-100-5p/ mammalian target of rapamycin (mTOR) axis.ResultsWe showed that bone marrow derived macrophage (BMDM) derived-sEVs (BMDM-sEVs) from collagen-induced arthritis (CIA) mice (cBMDM-sEVs) exhibited a notable increase in abundance compared with BMDM-sEVs from normal mice (nBMDM-sEVs). cBMDM-sEVs induced significant RA-FLS proliferation and potent inflammatory responses. Mechanistically, decreased levels of miR-100-5p were detected in cBMDM-sEVs compared with nBMDM-sEVs. miR-100-5p overexpression ameliorated RA-FLS proliferation and inflammation by targeting the mTOR pathway. Partial attenuation of the inflammatory effects induced by cBMDM-sEVs on RA-FLS was achieved through the introduction of an overexpression of miR-100-5p.ConclusionsOur work reveals the critical role of macrophages in exacerbating RA by facilitating the transfer of miR-100-5p-deficient sEVs to RA-FLS, and sheds light on novel disease mechanisms and provides potential therapeutic targets for RA interventions.Graphical abstract

CD14+ Dendritic-Shaped Cells Functioning as Dendritic Cells in Rheumatoid Arthritis Synovial Tissues.

We previously reported that CD14+ dendritic-shaped cells exhibit a dendritic morphology, engage in pseudo-emperipolesis with lymphocytes, and express CD90 in the perivascular areas of rheumatoid arthritis (RA) synovial tissues. However, it remains unclear whether these CD14highCD90intermediate(int) cells function as dendritic cells. In this study, we investigated the dendritic cell-differentiation potential of CD14highCD90int cells. The localization and number of CD14highCD90int cells in RA synovial tissues and peripheral blood were examined. The dendritic cell-differentiation potential of CD14highCD90int cells was examined by measuring interleukin-6 and tumor necrosis factor-α levels in the supernatant and CD83 and human leukocyte antigen (HLA)-DR expression in the cells after induction of dendritic cell differentiation. Synovial cells were co-cultured with lymphocytes, and the activation of these cells was examined. CD14highCD90int cells were abundant in RA synovial tissues, including the sublining layer and the pannus areas. Patients with untreated and active RA had significantly higher percentages of CD14highCD90int cells in the peripheral blood and synovial tissues. In RA synovial cells, inflammatory cytokine levels increased with dendritic cell-differentiation culture, but CD83 and HLA-DR expression were significantly increased in the CD14highCD90int cell group. When co-cultured with lymphocytes, cell numbers and inflammatory cytokine levels significantly increased in both groups of synovial cells after dendritic cell induction. CD14+ cells migrate and spread from the circulating blood to RA synovial tissues while expressing CD90, and CD14highCD90int cells in contact with lymphocytes differentiate into HLA-DR+ dendritic cells, which contribute to chronic inflammation in RA.

Unveiling the Nexus: Cellular Metabolomics Unravels the Impact of Estrogen on Nicotinamide Metabolism in Mitigating Rheumatoid Arthritis Pathogenesis.

Rheumatoid arthritis (RA) is a metabolic joint disorder influenced by hormonal regulation, notably estrogen, which plays a cytoprotective role against inflammation. While estrogen's impact on RA pathogenesis has been studied, the altered metabolite expression under estrogen's influence remains unexplored. This study investigated the changes in the metabolome of synovial fibroblasts isolated from RA patients under 17β-estradiol (E2) using the liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach followed by multivariate and biological pathway analysis along with in vitro validation. Results identified 3624 m/z, among which eight metabolites were significant (p < 0.05). Nicotinate and nicotinamide metabolism was found to be highly correlated with the treatment of E2, with metabolites NAD+ and 1-methynicotinamide (1-MNA) upregulated by E2 induction in RA-FLS. PharmMapper analysis identified potential gene targets of 1-MNA, which were further matched with RA gene targets, and thus, STAT1, MAPK14, MMP3, and MMP9 were concluded to be the common targets. E2 treatment affected the expression of these gene targets and ameliorated the development of oxidative stress associated with RA inflammation, which can be attributed to increased concentration of 1-MNA. Thus, an LC-MS/MS-based metabolomics study revealed the prominent role of estrogen in preventing inflammatory progression in RA by altering metabolite concentration, which can support its therapeutic capacity in remitting RA.

Effect of Integrated Naturopathy Interventions on Systemic Inflammatory Markers and Quality of Life in Patients With Active Rheumatoid Arthritis: A Randomized Controlled Trial.

Rheumatoid arthritis (RA) is a chronic, systemic, polyarticular autoimmune inflammatory disease that destroys the capsule and synovial lining of joints. Antirheumatic treatment reduces disease activity and inflammation, but not all patients respond to treatment. Naturopathy, a research-based complementary and alternative medicine, may be useful in these patients, but there is little data on the effect of Naturopathy interventions on inflammation and disease activity in RA. To explore the effect of 12 weeks of integrated naturopathy interventions on disease-specific inflammatory markers and quality of life in RA patients. A total of 100 RA patients were randomized into two groups: the naturopathy group (integrated naturopathy interventions with routine medical therapy) and the control group (only with routine medical therapy). Blood samples were collected pre- and post-intervention for primary outcome measurements of systemic inflammatory markers (ESR, CRP, and IL-6). Disease activity score (DAS-28) and quality of life were used to assess disease activity and functional status using SF-36, respectively, at pre- and post-intervention time points. The results of the present study show a notable decrease in disease activity after 12 weeks of naturopathy intervention. As such, a significant decrease was found in levels of systemic inflammatory markers such as ESR (p = 0.003)and IL-6 (p < 0.001), RA disease activity score (DAS-28) (p = 0.02), and most of the components of health-related quality of life (SF 36 scores) (p < 0.05) except in vitality (p = 0.06). Conclusions: The findings of the present study suggest that integrated naturopathy treatments may have the ability to control persistent inflammation, maintain immune homeostasis, and lower disease activity.

Moxibustion of Zusanli (ST36) and Shenshu (BL23) alleviates the inflammation of rheumatoid arthritis in rats through regulating macrophage migration inhibitory factor/glucocorticoids signaling.

To test the hypothesis that moxibustion may inhibit rheumatoid arthritis (RA) synovial inflammation by regulating the expression of macrophage migration inhibitory factor (MIF)/glucocorticoids (GCs). Fifty male Sprague-Dawley rats were randomly divided into five groups (n = 10 each): blank Control (CON) group, RA Model (RA) group, Moxibustion (MOX) group, MIF inhibitor (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) group, and Moxibustion + MIF inhibitor ISO-1 (MOX + ISO-1) group. Rats in the ISO-1 group and ISO-1 + MOX group were intraperitoneally injected with the inhibitor ISO-1. The rats in the RA group, ISO-1 group, MOX group, and ISO-1 + MOX group were injected with Freund's complete adjuvant (FCA) in the right hind footpad to establish an experimental RA rat model. In the MOX group and MOX + ISO-1 group, rats were treated with Moxa. The thickness of the footpads of the rats in each group was measured at three-time points before, after modeling and after moxibustion treatment. The contents of serum MIF, corticosterone (CORT), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay; and the contents of synovial MIF were detected by Western blot. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes of synovial tissue under a section light microscope, and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease. Moxibustion was found to reduce the level of MIF and alleviate inflammation in RA rats in this study. In addition, after inhibiting the expression of MIF, the level of CORT increased, and the level of TNF-α decreased. Treating RA rats with inhibited MIF by moxibustion, the level of CORT was almost unchanged, but the level of TNF-α further decreased. The correlation analysis data suggested that MIF was positively related to the expression of TNF-α and negatively correlated with the expression of CORT. Reducing MIF to increase CORT and decrease TNF-α by moxibustion treatment in RA. MIF may be a factor for moxibustion to regulate the expression of CORT, but the expression of TNF-α is due to the incomplete regulation of the MIF. This study added to the body of evidence pointing to moxibustion's anti-inflammatory mechanism in the treatment of RA.

Clinical implications of seropositive and seronegative autoantibody status in rheumatoid arthritis patients: A comparative multicentre observational study.

Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA.

Functional results of total knee prosthesis in the treatment of rheumatoid arthritis: A case report of 64 patients

This is a retrospective study of 64 total knee arthroplasties for inflammatory rheumatism, implanted in the Traumatology and Orthopedic Surgery Department (A) of the HASSAN II University Hospital in Fez Morocco, from February 2008 to December 2022. The aim of our work is to demonstrate the value of total knee arthroplasty in improving the quality of life of young patients with inflammatory rheumatic diseases, notably through pain relief and improved joint mobility. Our series included 44 patients, representing 64 arthroplasties. The mean age at the time of surgery was 48 years. All our patients were followed up at the consultation with a clinical and radiological examination. The IKS score was used to assess knee condition before and after surgery. The surgical procedure consisted of total knee arthroplasty using a total knee arthroplasty. Clinical results after a mean follow-up of 60 months were satisfactory, with a marked improvement in the postoperative IKS score.

Emotional repression in patients with chronic inflammatory rheumatism

Background: A person’s psychological background may support and direct the inflammatory evolution of a disease toward a specific type of chronic inflammatory rheumatism (CIR). Aim: This study aimed to identify a particular emotional profile of patients with CIR, particularly rheumatoid arthritis (RA) and spondyloarthritis (SpA), based on psychological profile assessments between patients with and without CIR. Emotional repression, that is, a tendency to inhibit the expression of negative feelings and/or unpleasant thoughts, was particularly studied. Methods: This monocentric observational pilot study included patients from the rheumatology department of a university hospital. These patients were systematically assessed for different psychological parameters by an experienced psychiatrist, and their clinical and biological characteristics were collected accordingly. Data analysis was performed using the Chi-squared test or Fisher’s exact test. Results: Fifty-nine patients were assessed: 47 patients with CIR (i.e., 27 with RA and 20 with SpA) (CIR group) and 12 non-CIR patients (i.e., nine with osteoarthritis, one with viral disease, one with osteoporosis, and one with osteomalacia) (control group). Severe emotional repression and early life events were both significantly higher in the CIR group than in the control group (P = 0.02). In contrast, severe psychological and somatic complaints were significantly higher in the control group than in the CIR group (P &lt; 0.01 and P = 0.01, respectively). Conclusion: Our findings suggested that emotional repression from traumatic life events could aggravate the etiology and/or course of CIR. Therefore, appropriate psychological care should have a relevant place within the current therapeutic options for the clinical management of CIR. Relevance for Patients: The management of CIR should include psychological support as learning coping mechanisms can facilitate the recovery of CIR patients.