Rheumatoid Arthritis Joint Research Articles

Hyaluronic acid-based M1 macrophage targeting and environmental responsive drug releasing nanoparticle for enhanced treatment of rheumatoid arthritis

Herein, hyaluronic acid (HA) and β-cyclodextrin (β-CD) is used to form targeted drug delivery platform HCPC/DEX NPs with previously prepared carbon dots (CDs) as cross-linker, dexamethasone (DEX) is loaded for rheumatoid arthritis (RA) treatment. The drug loading capacity of β-CD and M1 macrophage targeting of HA were utilized for efficient delivery of DEX to the inflammatory joints. Because of the environmental responsive degradation of HA, DEX can be released in 24 h and inhibit the inflammatory response in M1 macrophages. The drug loading of NPs is 4.79 %. Cellular uptake evaluation confirmed that NPs can specifically target to M1 macrophages via HA ligands, the uptake of M1 macrophages is 3.7 times that of normal macrophages. In vivo experiments revealed that NPs can accumulate in RA joints to alleviate inflammation and accelerate cartilage healing, the accumulation can be observed in 24 h. The cartilage thickness increased to 0.45 mm after HCPC/DEX NPs treatment, indicating its good RA therapeutic effect. Importantly, this study was the first to utilize the potential acid and reactive oxygen species responsiveness of HA to release drug and prepare M1 macrophage targeting nanodrug for RA treatment, which provides a safe and effective RA therapeutic strategy.

Patterns of Involvement of the Hand Joints in Classical Rheumatoid Arthritis.

Symmetrical involvement of the hand joints is described as characteristic of rheumatoid arthritis (RA). Quantitative data on specific patterns of involvement are lacking. The Brigham Rheumatoid Arthritis Sequential Study was created for observational studies of patients with RA and afforded a unique opportunity to answer these questions. Of 1598 subjects in the Brigham Rheumatoid Arthritis Sequential Study cohort, 535 met the following criteria: (1) disease duration of 7 years or greater, (2) seropositive, and (3) hand radiographs available. Patterns in specific hand joints based on physical examination and radiographic findings obtained at entry were identified. The level of symmetry of involvement of the metacarpophalangeal (MCP) and wrist joints was determined, as was the correlation between findings on physical examination and radiographic changes in the hand joints. The prevalence of joint space narrowing and/or erosions in each proximal interphalangeal (PIP) joints ranged between 11% and 18%. Joint space narrowing and/or erosions in the MCPs increased radially from the fifth to the second finger. Swelling and tenderness on physical examination of both the PIPs and MCPs also increased radially although the positive predictive value of physical examination as an indicator of joint damage decreased radially. The wrist was the most common joint involved both by physical examination (67%) and radiographically (70%). The right side was more involved radiographically. Analysis of radiographic changes in individual patients revealed that symmetrical findings in the wrists and MCPs occurred in only 67% of patients. The study describes the pattern of involvement of the hand joints in patients with long standing RA. Findings of interest include symmetrical involvement in only 67% of patients and a discordancy between physical findings and radiographic changes most marked in the more radial PIP joints.

An update on thermal imaging in rheumatoid arthritis.

This review aims to summarise the recent literature concerning the usage of thermal imaging in the study of rheumatoid arthritis (RA). Most RA studies have applied thermal imaging as a static process alone although thermal imaging has been conducted with an additional dynamic/functional component. Algorithms to automate the analysis of thermal imaging in RA have also been described. Several RA thermal imaging studies have demonstrated differences in thermographic findings between RA patients and healthy controls and/or compared thermographic parameters with other clinical/functional/imaging parameters; while fewer studies have assessed the role of thermal imaging in discriminating disease severity in RA. Thermal imaging is a relatively low cost, non-invasive imaging technique offering an objective measurement of joint surface temperature in RA joint inflammation assessment. Although there has been an increasing literature build up on the use of thermography in RA, more validation work is still necessary to delineate the potential role(s) of its use among patients with RA. This timely review focusses on the recent literature concerning thermal imaging, and provides clinicians with an update on its recent development in RA.

Psoriatic and rheumatoid arthritis joints differ in the composition of CD8+ tissue-resident memory T cell subsets

CD69+CD103+ tissue-resident memory T (TRM) cells are important drivers of inflammation. To decipher their role in inflammatory arthritis, we apply single-cell, high-dimensional profiling to Tcells from the joints of patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA). We identify three groups of synovial CD8+CD69+CD103+ TRM cells: cytotoxic and regulatory T (Treg)-like TRM cells are present in both PsA and RA, while CD161+CCR6+ type 17-like TRM cells with a pro-inflammatory cytokine profile (IL-17A+TNFα+IFNγ+) are specifically enriched in PsA. In contrast, only one population of CD4+CD69+CD103+ TRM cells is detected and at similarly low frequencies in both diseases. Type 17-like CD8+ TRM cells have a distinct transcriptomic signature and a polyclonal, but distinct, TCR repertoire. Type 17-like cells are also enriched in CD8+CD103- Tcells in PsA compared with RA. These findings illustrate differences in the immunopathology of PsA and RA, with a particular enrichment for type 17 CD8+ Tcells in the PsA joint.

"The Place of Osteoimmunology in the Pathogenesis of Rheumatic Joint and Bone Diseases"

"The Place of Osteoimmunology in the Pathogenesis of Rheumatic Joint and Bone Diseases"

The effect of JuanBiQiangGu granules in combination with methotrexate on joint inflammation in rheumatoid arthritis: a randomized controlled trial.

Background: Rheumatoid arthritis (RA) joint inflammation severely affects joint function and quality of life in patients and leads to joint deformities and limb disability. The non-steroidal anti-inflammatory drugs used in the treatment of RA do not fully control the progression of joint inflammation and bone destruction and have notable adverse reactions. Traditional Chinese medicine formula JuanBiQiangGu Granules (JBQG) are commonly used for the treatment of RA inflammation and delay of bone destruction, but has not been evaluated through high-quality clinical studies. There is a pressing need for well-designed, randomized, parallel, controlled clinical studies to evaluate the exact effect of JBQG on RA joint inflammation and improvement of patient quality of life. Methods: This is a randomized, parallel, controlled clinical study in which 144 patients with rheumatoid arthritis who met the inclusion criteria were randomly assigned to 2 groups in a 1:1 ratio. The JBQG group received methotrexate 7.5mg qw and JBQG granules 8mg tid, while the MTX group received methotrexate 7.5mg qw. The endpoint was 12weeks after treatment. Relevant indices at baseline, 4weeks, 8weeks, and 12weeks after treatment were observed and recorded, and DAS28-ESR, HAQ-DI, and Sharp scores were recorded for each patient. Blood samples were collected to test for CRP, ESR, TNF-α, IL-1β, IL-6, IL-17, and INF-γ, and adverse reactions and liver and kidney function (AST, ALT, Cr, BUN) were recorded for safety assessment. After 12weeks of treatment, the effect of JBQG granules on disease activity, improvement in bone damage, and patient quality of life scores and safety in RA patients were evaluated. Results: A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators (p > 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR levels below or equal to Low, including 45.07% in Remission and 5.63% in High, compared to 53.1% in the MTX group below or equal to Low, 12.33% in Remission, and 17.81% in High. CRP was significantly reduced (8.54 ± 5.87 vs. 11.86 ± 7.92, p < 0.05, p = 0.005), ESR was significantly reduced (15.1 ± 6.11 vs. 21.96 ± 9.19, p < 0.0001), TNF-α was significantly reduced (1.44 ± 0.83 vs. 1.85 ± 1.07, p < 0.05, p = 0.011), IL-17 was significantly reduced (0.53 ± 0.33 vs. 0.71 ± 0.38, p < 0.05, p = 0.004), and INF-γ was significantly reduced (3.2 ± 1.51 vs. 3.89 ± 1.77, p < 0.05, p = 0.014). The median (IQR) OPG in the JBQG group was 2.54 (2.21-3.01), significantly higher than in the MTX group 2.06 (1.81-2.32), p < 0.0001), and the median (IQR) β-CTX in the JBQG group was 0.4 (0.32-0.43), significantly lower than in the MTX group 0.55 (0.47-0.67), p < 0.0001). The median (IQR) VSA scores were 2 (1-3), a decrease from 3 (2-4) in the MTX group (p < 0.0001). The median (IQR) Sharp scores were 1 (1-2), a decrease from 2 (1-2) in the MTX group, but the difference was not statistically significant (p > 0.05, p = 0.28). The median (IQR) HAQ-DI scores were 11 (8-16), significantly lower than in the MTX group 26 (16-30) (p < 0.0001). The median (IQR) AST in the JBQG group was 16 (12-20), with a significant difference compared to the MTX group 19 (13-25) (p < 0.01, p = 0.004); the median (IQR) ALT in the JBQG group was 14 (10-18), with a significant difference compared to the MTX group 16 (11-22.5) (p < 0.05, p = 0.015). There were no statistically significant differences in Cr or BUN (p > 0.05). Conclusion: JuanBiQiangGu Granules can be used to treat patients with rheumatoid arthritis, alleviate joint inflammation, reduce the incidence of adverse reactions to methotrexate, and has good safety. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html; identifier: ChiCTR2100046373.

The Search for the Pathogenic T Cells in the Joint of Rheumatoid Arthritis: Which T-Cell Subset Drives Autoimmune Inflammation?

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting systemic synovial tissues, leading to the destruction of multiple joints. Its etiology is still unknown, but T-cell-mediated autoimmunity has been thought to play critical roles, which is supported by experimental as well as clinical observations. Therefore, efforts have been made to elucidate the functions and antigen specificity of pathogenic autoreactive T cells, which could be a therapeutic target for disease treatment. Historically, T-helper (Th)1 and Th17 cells are hypothesized to be pathogenic T cells in RA joints; however, lines of evidence do not fully support this hypothesis, showing polyfunctionality of the T cells. Recent progress in single-cell analysis technology has led to the discovery of a novel helper T-cell subset, peripheral helper T cells, and attracted attention to the previously unappreciated T-cell subsets, such as cytotoxic CD4 and CD8 T cells, in RA joints. It also enables a comprehensive view of T-cell clonality and function. Furthermore, the antigen specificity of the expanded T-cell clones can be determined. Despite such progress, which T-cell subset drives inflammation is yet known.

Partnering with people living with rheumatoid arthritis for care of their hands: Four case reports using relative motion orthoses

Study DesignCase report. IntroductionDespite better disease control with more effective medications, people with rheumatoid arthritis (RA) continue to experience persistent and fluctuating levels of pain, swelling and functional limitations in their hands. PurposeTo describe therapists and people living with RA working together to understand what could be occurring in their hands because of the RA and how relative motion (RM) orthoses may be used to self-manage common hand RA related problems. MethodsCase reports are used to demonstrate how patient self-report, clinical exam, and observation of hand movement and function are integrated into the design of RM orthoses for individuals with RA. The cases are supported by photos and videos, including a personal narrative video exploring 1 persons’ personal perspective on their use of RM orthoses. ResultsCase reports illustrate adaptive and/or protective RME orthoses use for RA related finger malalignment, tendon subluxation, joint pain and instability in the hand. The narrative video also introduces a person living with RA, who speaks candidly about her multiple RM orthoses and how she decides which orthosis is “best” for a given activity and the current level of RA related problems in her hands. DiscussionIt is not unusual for individuals with RA to have multiple RM orthoses, made for different purposes and fabricated from different materials. Mulitple RM orthosis options allows a person to select what is “best” for them, depending on the context of use and priorities or needs. ConclusionPartnering with people living with RA to understand how to use simple, low-profile, adaptive and protective RM orthoses may be an effective way to support self-management of common RA related hand problems.

Arthroscopic synovectomy versus intra-articular injection of corticosteroids for the management of refractory psoriatic or rheumatoid arthritis of the wrist: study protocol for a randomized controlled trial (ARCTIC trial)

BackgroundRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up.MethodsThis protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0–100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups.DiscussionPersistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI.Trial registrationDutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020.ClinicalTrials.gov NCT04755127. Registered after the start of inclusion on 15 February 2021.

Integrated Immune Cell-Cell Communication Networks Underpinning Rheumatoid Arthritis Pathogenesis

Rheumatoid Arthritis (RA) is a chronic, systemic auto-inflammatory disease that targets peripheral joints causing bone erosion, worsened mobility, and lower quality of life. RA is a complex autoimmune disease that develops through the combined actions of many cell types. In particular, monocytes, fibroblasts, and T cells play critical roles within the arthritic joint driving disease pathogenesis. These cells communicate with each other via ligand-receptor interactions orchestrating inflammatory responses ultimately leading to joint destruction. However, it remains unclear how the combined efforts of these different cells form an integrated network of immune responses which ultimately lead to disease development. Therefore, we hypothesized that an integrated communication network between the different immune cells found within RA joints functions to promote inflammation and drive RA disease pathogenesis. I utilized predictive assessment of cell-cell communication networks through single-cell RNA-sequencing to determine how immune cell interactions differ between autoimmune and non-autoimmune joint destruction. These studies identified a novel cell-cell communication network in which monocytes, fibroblasts and T cells cooperate to promote cell-cell interactions, immune activation, and induction of pro-inflammatory gene networks. Together, these results identify numerous potential therapeutic targets for the intervention of RA disease.

Diversity and Clonality of T Cell Receptor Repertoire and Antigen Specificities in Small Joints of Early Rheumatoid Arthritis.

CD4+ T cells are implicated in rheumatoid arthritis (RA) pathology from the strong association between RA and certain HLA class II gene variants. This study was undertaken to examine the synovial T cell receptor (TCR) repertoire, T cell phenotypes, and T cell specificities in small joints of RA patients at time of diagnosis before therapeutic intervention. Sixteen patients, of whom 11 patients were anti-citrullinated protein antibody (ACPA)-positive and 5 patients were ACPA-, underwent ultrasound-guided synovial biopsy of a small joint (n=13) or arthroscopic synovial biopsy of a large joint (n=3), followed by direct sorting of single T cells for paired sequencing of the αβ TCR together with flow cytometry analysis. TCRs from expanded CD4+ T cell clones of 4 patients carrying an HLA-DRB1*04:01 allele were artificially reexpressed to study antigen specificity. T cell analysis demonstrated CD4+ dominance and the presence of peripheral helper T-like cells in both patient groups. We identified >4,000 unique TCR sequences, as well as 225 clonal expansions. Additionally, T cells with double α-chains were a recurring feature. We identified a biased gene usage of the Vβ chain segment TRBV20-1 in CD4+ cells from ACPA+ patients. In vitro stimulation of T cell lines expressing selected TCRs with an extensive panel of citrullinated and viral peptides identified several different virus-specific TCRs (e.g., human cytomegalovirus and human herpesvirus 2). Still, the majority of clones remained orphans with unknown specificity. Minimally invasive biopsies of the RA synovium allow for single-cell TCR sequencing and phenotyping. Clonally expanded, viral-reactive T cells account for part of the diverse CD4+ T cell repertoire. TRBV20-1 bias in ACPA+ patients suggests recognition of common antigens.

Serum sirtuin-1 a potential marker in the diagnosis of rheumatoid arthritis

Introduction: To explore the value of serum sirtuin-1 (SIRT1) in the diagnosis and evaluation of joint mobility of rheumatoid arthritis (RA). Materials and Methods: Serum was randomly obtained from 212 RA patients,210 non-RA patients and 58 healthy controls in a large tertiary first-class hospital in Jiangxi province from November 2021 to June 2022. The level of serum Sirt1,anti-cyclic citrulline polypeptide antibody (anti-CCP), anti-mutant citrulline vimentin antibody (anti-MCV), rheumatoid factor (RF),high-mobility group box 1 (HMGB1), collagen triple helix repeat containing 1 (CTHRC1), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by ELISA, to explore the correlation between them and their value in the diagnosis and evaluation of joint range of motion of RA and statistically analyse their diagnostic efficiency. Results: ① The level of all markers was higher in the RA group than in the non-RA group and the healthy controls (p < 0.05). ② The AUC of the SIRT1 was 0.882, second only to the anti-MCV and anti-CCP. ③ The anti-CCP showed the highest sensitivity to RA diagnosis of 0.948. The specificity and positive predictive value of SIRT1 for the diagnosis of RA were the highest, which are 0.959 and 0.934 respectively. ④ In serial combination, SIRT1/anti-CCP、SIRT1/anti-MCV showed the highest specificity.SIRT1/anti-CCP in parallel combination had the highest sensitivity. ⑤ SIRT1 showed a significant correlation with other markers and DAS28 scores (p < 0.01). Conclusion: SIRT1 can be used as a new serological marker for RA diagnosis, which has a significant correlation with RA joint mobility and has a certain reference value in RA differential diagnosis, providing a new detection basis for RA differential diagnosis.

Power doppler ultrasound signal predicts abnormal HDL function in patients with rheumatoid arthritis

Active rheumatoid arthritis (RA) is associated with increased cardiovascular risk and impaired function of high-density lipoprotein (HDL). Previous work suggests that HDL may become dysfunctional through oxidative modifications within the RA joint. The current work evaluates an association of synovial power doppler ultrasound signal (PDUS) with HDL function and structure. Two open-label clinical therapeutic studies using PDUS as a disease outcome measure were included in this analysis, including a 12-month trial of subcutaneous abatacept in 24 RA patients and a 6-month trial of IV tocilizumab in 46 RA patients. Laboratory assays included assessments of HDL function and structure, HDL and total cholesterol levels, and a cytokine/chemokine panel. Patients with the highest baseline PDUS scores in both clinical studies, had worse HDL function, including suppression of paraoxonase 1 (PON1) activity as well as lower HDL-C levels. Associations between other disease assessments (DAS28 and CDAI) and HDL function/structure were noted but were generally of lesser magnitude and consistency than PDUS across the HDL profile. Treatment with tocilizumab for 6 months was associated with increases in cholesterol levels and improvements in the HDL function profile, which correlated with greater decreases in PDUS scores. Similar trends were noted following treatment with abatacept for 3 months. Higher baseline PDUS scores identified patients with worse HDL function. This data supports previous work suggesting a direct association of joint inflammation with abnormal HDL function.

The Influence of Adipokines on Radiographic Damage in Inflammatory Rheumatic Diseases

Inflammatory rheumatic diseases (IRDs) are complex immune-mediated diseases that are characterized by chronic inflammation of the joints. Rheumatoid arthritis (RA) and spondyloarthritis (SpA), including axial SpA (ax SpA) and psoriatic arthritis (PsA), are the most common forms of IRD. Both RA and ax SpA are characterized by a chronic course with progressive structural modifications, namely, cartilage damage and bone erosions in RA and osteoproliferative changes with spinal ossifications in ax SpA. The adipose tissue is involved in the pathophysiology of IRDs via the release of several proteins, namely, adipokines. Several adipokines with pro-inflammatory effects have been identified, such as leptin, adiponectin, visfatin and resistin. In this review, we discuss the role that adipokines may play in the structural modifications of the peripheral joints and/or axial skeleton. In RA, the role of leptin in structural damage remains controversial, while adiponectin and its high-molecular-weight isoform are known to have an influence on the development of bone erosions and radiographic progression. Resistin also appears to be a potent detrimental adipokine for the joints in RA. In ax SpA, visfatin seems to be an attractive candidate for radiographic progression, while leptin and adiponectin have negative effects on radiographic progression.

Identification of key candidate genes and pathways in rheumatoid arthritis and osteoarthritis by integrated bioinformatical analysis.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common joint disorders. Although they have shown analogous clinical manifestations, the pathogenesis of RA and OA are different. In this study, we used the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE153015 to identify gene signatures between RA and OA joints. The relevant data on 8 subjects obtained from large joints of RA patients (RA-LJ), 8 subjects obtained from small joints of RA patients (RA-SJ), and 4 subjects with OA were investigated. Differentially expressed genes (DEGs) were screened. Functional enrichment analysis of DEGs including the Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, which were mainly associated with T cell activation or chemokine activity. Besides, protein-protein interaction (PPI) network analysis was performed, and key modules were identified. Hub genes of RA-LJ and OA groups were screened, they were CD8A, GZMB, CCL5, CD2, and CXCL9, whereas CD8A, CD2, IL7R, CD27, and GZMB were hub genes of RA-SJ and OA group. The novel DEGs and functional pathways between RA and OA identified in this study may provide new insight into the underlying molecular mechanisms and therapeutic strategies of RA and OA.

Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation, pannus formation, and bone and cartilage damage. It has a high disability rate. The hypoxic microenvironment of RA joints can cause reactive oxygen species (ROS) accumulation and mitochondrial damage, which not only affect the metabolic processes of immune cells and pathological changes in fibroblastic synovial cells but also upregulate the expression of several inflammatory pathways, ultimately promoting inflammation. Additionally, ROS and mitochondrial damage are involved in angiogenesis and bone destruction, thereby accelerating RA progression. In this review, we highlighted the effects of ROS accumulation and mitochondrial damage on inflammatory response, angiogenesis, bone and cartilage damage in RA. Additionally, we summarized therapies that target ROS or mitochondria to relieve RA symptoms and discuss the gaps in research and existing controversies, hoping to provide new ideas for research in this area and insights for targeted drug development in RA.

Inflammation specific environment activated methotrexate-loaded nanomedicine to treat rheumatoid arthritis by immune environment reconstruction.

Rheumatoid arthritis (RA), as an autoimmune inflammatory disease, is featured by enhanced vascular permeability, irreversible cartilage destroys and bone erosion. Although the pathogenesis of RA is still unclear, the immune environment, particularly the lymphatic system, which is instrumental to immune cell surveillance and interstitial fluid balance, plays vital roles in the process of RA. Herein, an inflammation specific environment activated methotrexate-encapsulated nanomedicine (MTX@NPs) was constructed for RA treatment, which accumulated in inflamed joints, and released MTX in the specific RA microenvironment. Notably, MTX@NPs could regulate the immune environment including reducing the expressions of inflammatory cytokines of macrophages and the inflammatory level of lymphatic epithelial cells (LECs), and ameliorating the lymphatic vessel contraction and drainage. In vitro and In vivo studies illustrated that MTX@NPs exhibited a high RA therapeutic efficacy and insignificant systemic toxicity owing to the suppression of the inflammation response and the improved lymphatic functions of RA joints. It suggests that the nanomedicine paves a potential way to the clinical practice of autoimmune diseases treatments via the regulation of immune environment and lymphatic functions. STATEMENT OF SIGNIFICANCE: Although 1.0% of the population in the world suffers from rheumatoid arthritis (RA), the pathogenesis of RA is still unclear and the therapeutic effect of the first-line clinical drugs is relatively low. Herein, we propose a specific RA-microenvironment triggered nanomedicine (MTX@NPs), which enhances RA treatment of a first-line antirheumatic drug (methotrexate, MTX) by immune environment reconstruction. The nanomedicine exhibits RA joints accumulation by EPR effect, and releases MTX under the specific RA environment, leading to the dramatical drop of M1-type macrophages and acceleration of lymphatic vessel contraction and drainage. Finally, the inflammatory cytokines in RA immune environment are reduced sharply, indicating the outstanding therapeutic efficacy of MTX@NPs to RA.

Диагностические критерии поражения гортани при манифестации ревматоидного артрита

Introduction. Rheumatoid arthritis is a systemic autoimmune inflammation of connective tissue involving the cartilage of the larynx. In this case, pathology of the larynx may be the only manifestation of this disease. The discomfort, foreign body sensation, and pain in the larynx noted by patients in the early stages of the disease are rarely associated by doctors with the manifestation of rheumatoid arthritis. In later stages, symptoms may be masked as comorbid pathology of the heart or upper respiratory tract. An analysis of the available literature revealed insufficient knowledge of issues related to the early diagnosis of inflammation of the larynx in autoimmune diseases, in particular, rheumatoid arthritis. Objective. To conduct a literature review to identify early symptoms of laryngeal damage in patients with the manifestation of rheumatoid arthritis. Materials and methods. Over the past 10 years, a literature review has been conducted in public databases using the following queries: laryngeal injury in autoimmune rheumatic diseases, dysphonia, voice impairment in rheumatoid arthritis, rheumatoid arthritis, and laryngeal joint injury. Data from literature sources, the authors of which made a significant contribution to the development of otorhinolaryngology and rheumatology, were included. Results. Summary data from the literature review are presented on the frequency of complaints made by patients, verification of characteristic symptoms, and their severity depending on the level of damage to the larynx. An early symptom of the manifestation of rheumatoid arthritis is dysphonia, which was observed with inflammation of the cricoarytenoid joints, arytenoid cartilage, and vocal fold nodules. A checklist of early symptoms of laryngeal injury has been compiled for routing patients with rheumatoid arthritis. Conclusion. Laryngeal involvement in rheumatoid arthritis is a fairly common symptom. Dysphonia as an early symptom is observed with polymorphism of inflammatory changes and manifests itself from single nodules to total fixation of the joints of the laryngeal cartilage. In diagnosing the manifestations of rheumatoid arthritis, an interdisciplinary approach of specialists is required.

Enhancement of anti-inflammatory and anti-tumorigenic properties of 3D-spheroid formed mesenchymal stem cells derived from rheumatoid arthritis joints

Seung-Chan Lee, Chae-Yeon Hong, Yong-Ho Choe, Tae-Seok Kim, Won-Jae Lee, Gyu-Jin Rho and Sung-Lim Lee. Journal of Animal Reproduction and Biotechnology 2022;37:246-54. https://doi.org/10.12750/JARB.37.4.246

Anti-protein arginine deiminase antibodies are distinctly associated with joint and lung involvement in rheumatoid arthritis.

RA is a chronic inflammatory disease in which possible interstitial lung disease (ILD) is an extra-articular manifestation that carries significant morbidity and mortality. RF and ACPA are included in the RA classification criteria but prognostic and diagnostic biomarkers for disease endotyping and RA-ILD are lacking. Anti-protein arginine deiminase antibodies (anti-PAD) are a novel class of autoantibodies identified in RA. This study aimed to assess clinical features, ACPA and anti-PAD antibodies in RA patients with articular involvement and ILD. We retrospectively collected joint erosions, space narrowing, clinical features and lung involvement of a cohort of 71 patients fulfilling the 2010 ACR/EULAR RA classification criteria. Serum samples from these patients were tested for ACPA IgG (QUANTA Flash CCP3), and anti-PAD3 and anti-PAD4 IgG, measured with novel assays based on a particle-based multi-analyte technology (PMAT). Anti-PAD4 antibodies were significantly associated with radiographic injury (P = 0.027) and erosions (P = 0.02). Similarly, ACPA levels were associated with erosive disease (P = 0.014). Anti-PAD3/4 double-positive patients displayed more joint erosions than patients with anti-PAD4 antibodies only or negative for both (P = 0.014 and P = 0.037, respectively). RA-ILD (15.5%, 11/71 patients) was associated with older age (P < 0.001), shorter disease duration (P = 0.045) and less erosive disease (P = 0.0063). ACPA were elevated in RA-ILD, while anti-PAD4 were negatively associated (P = 0.043). Anti-PAD4 and anti-PAD3 antibodies identify RA patients with higher radiographic injury and bone erosions. In our cohort, ILD is associated with lower radiographic and erosive damage, as well as low levels of anti-PAD4 antibodies.