Course Of Rheumatoid Arthritis Research Articles

Relationship between the level of antibodies to the RA-33 antigen and the course of rheumatoid arthritis

Relationship between the level of antibodies to the RA-33 antigen and the course of rheumatoid arthritis

Reactive Oxygen and Nitrogen Species - "Nanosweeper" for Rheumatoid Arthritis Theranostics by Macrophage Reprogramming.

Excessive reactive oxygen and nitrogen species (RONS) accumulation in joints are significant variables that affect the course of rheumatoid arthritis (RA). Scavenging of RONS to remodel macrophage homeostasis is a potentially powerful treatment for RA. Here, a visualized "nanosweeper" by functionalizing ultrasmall Gd/Fe3O4 nanoparticles with thiol-polyethylene glycol-phosphoric acid and 2-(3-(2-aminophenyl)ureido) ethyl methacrylate hydrochloride (APUEMA), namely GIA NPs, can simultaneously scavenge both nitric oxide (NO) and reactive oxygen species (ROS), as well as enhance magnetic resonance imaging (MRI) for the diagnosis and therapy of RA. GIA NPs could not only eliminate NO by reactions between the o-phenylenediamine moieties of APUEMA and NO molecules but also remove ROS by the superoxide peroxidase activities of the Fe3O4 nanoparticles and thiol. In vitro and in vivo experiments revealed that the simultaneous scavenging of NO and ROS strategy inhibited the overactivation of the cyclic guanosine monophosphate/protein kinase G (cGMP/PKG) signaling pathway to reprogram the polarization states of macrophages and interfered with metabolism to alleviate RA. In addition, GIA NPs, as dual-modal nanoprobes for MRI, exhibited the capacity for the early diagnosis of RA lesions and monitoring during the RA treatment process. The visualized "nanosweeper" strategy provides a promising integrated platform for the diagnosis and treatment of RA.

Therapeutic efficacy of brown propolis fromAraucaria sp.in modulating rheumatoid arthritis.

Rheumatoid arthritis is a systemic inflammatory autoimmune disease with prevalence estimated at 0.5% to 1% of the population. As one of the treatment routes of rheumatoid arthritis is based on the use of nonsteroidal anti-inflammatory drugs, the use of natural products with anti-inflammatory potential becomes relevant. Brown propolis has several biological properties, including immunomodulatory and anti-inflammatory effects. Thus, the present study evaluated the therapeutic efficacy of the crude extract of brown propolis from Araucaria sp. through experimental models of analgesia, anti-inflammatory activity, and rheumatoid arthritis. Hyperalgesia was evaluated by mechanical and thermal sensitivity. Anti-inflammatory activity was evaluated by plantar volume, cell migration and NF-kB expression in carrageenan-induced paw oedema. In collagen-induced rheumatoid arthritis, it was evaluated by mechanical and thermal nociception on the plantar surface, and mechanical nociception in the femorotibial and caudal joints, evaluation of plantar volume, radiography, weight gain and biochemical profile. The results demonstrated that the oral administration of brown propolis can modulate the course of rheumatoid arthritis, and it can inhibit pain through the modulation of mechanical sensitivity. The anti-arthritic effect of propolis may be due to its anti-inflammatory capacity, which includes inhibiting oedema formation, cell migration, and NF-kB expression, as well as preserving joint space and normalizing urea levels. This was an animal model study. Therefore, brown propolis should be evaluated in studies of human RA to determine efficacy.

ПРОБИОТИКТЕР РЕВМАТОИДТЫ АРТРИТТІҢ ҚОСЫМША ЕМІ РЕТІНДЕ. ӘДЕБИЕТКЕ ШОЛУ.

Relevance. Rheumatoid arthritis (RA) is a condition with an unclear cause, marked by inflammation affecting the synovial tissue of joints, cartilage, and bone. RA can extend to areas outside the joints,autoantibodies production and progressive disability. Rheumatoid arthritis affects approximately 0.24% to 1% of adults globally, with women being affected 2 to 3 times more frequently than men. In recent years numerouse studies showed the significant role of micribiome in RA developement. Regardless of using disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapies, a significant number of patients with RA fail to achieve remission. These two facts have prompted interest in targeting the microbiome as a therapeutic strategy for RA. Aim: To analyze the effectiveness of probiotics in the treatment of RA according to contemporary literature. Search strategy: A search for scientific publications was carried out in the following databases of scientific publications and specialized search engines: PubMed, Google Scholar, Web of Science Core Collection, Cochrane Library. A number of original publicly available publications on the research topic were analyzed. The search depth was 10 years. As a result of the search, we studied 579 foreign publications, of which 84 publications were included in this review. Inclusion criteria: meta-analyses, systematic reviews, cohort and cross-sectional studies. Exclusion criteria: short reports, newspaper articles and expert opinion in the form of short reports. Results and conclusions: The review revealed that probiotics can influence the microbiome and immune system of RA patients through various mechanisms of action. In addition, it has been found that the use of L. Casei alone and in combination with L. acidophilus, L. Lactis, B. Lactis and B. bifidum, as well as Bacillus coagulans can improve the course of RA, reduce the level of inflammatory markers and pro-inflammatory cytokines. Given the conflicting evidence regarding the effectiveness of probiotics in the treatment of RA, further research is needed.

The Ability of Indigenous Plants in Alleviating Rheumatoid Arthritis: A Comprehensive Review.

Rheumatoid Arthritis is a long-lasted, inflammatory, systemic autoimmune disease that predominantly manifests in people between the ages of 30 and 50 Rheumatoid arthritis is characterized by more than a half-hour of morning stiffness in the affected joints, fever, soreness, swelling, weight loss, tiredness, warm joints, and subcutaneous rheumatoid nodules. Hormonal, genetic, epigenetic, reproductive, and neuroendocrine risk factors, as well as comorbid host variables, are the categories of host-related risk factors associated with the evolution of RA. Additional risk variables that have been linked to RA include food, environmental variables, socioeconomic status, smoking, microbiome, infection agents, and other airborne exposures. The objective of RA therapies is to minimise joint deformity and destruction, minimise discomfort and inflammation in the joints, and maximise joint function.Growing data suggests that the course of Rheumatoid Arthritis is affected by the minimisation of disease activity caused by disease-modifying medications, and that patients may benefit from early antirheumatic medication delivery that modifies illness. While numerous herbs have been explored for their anti-inflammatory properties, it is important to note that not all herbs have been thoroughly researched. This review focuses on seventeen native plant species that have shown either promising or established anti-arthritic effects based on preclinical and clinical studies where available. The review highlights the biochemical and immunological attributes of these herbs, summarizing their therapeutic potential for RA management while also acknowledging the limitations and gaps in current research. This examination provides insights into the potential of these herbal treatments for RA and calls for further research to explore their efficacy and safety in greater depth.

Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib

BackgroundPatients with rheumatoid arthritis (RA) have an increased risk of developing serious infections (SIs) vs. individuals without RA; efforts to predict SIs in this patient group are ongoing. We assessed the ability of different machine learning modeling approaches to predict SIs using baseline data from the tofacitinib RA clinical trials program.MethodsThis analysis included data from 19 clinical trials (phase 2, n = 10; phase 3, n = 6; phase 3b/4, n = 3). Patients with RA receiving tofacitinib 5 or 10 mg twice daily (BID) were included in the analysis; patients receiving tofacitinib 11 mg once daily were considered as tofacitinib 5 mg BID. All available patient-level baseline variables were extracted. Statistical and machine learning methods (logistic regression, support vector machines with linear kernel, random forest, extreme gradient boosting trees, and boosted trees) were implemented to assess the association of baseline variables with SI (logistic regression only), and to predict SI using selected baseline variables using 5-fold cross-validation. Missing values were handled individually per prediction model.ResultsA total of 8404 patients with RA treated with tofacitinib were eligible for inclusion (15,310 patient-years of total follow-up) of which 473 patients reported SIs. Amongst other baseline factors, age, previous infection, and corticosteroid use were significantly associated with SI. When applying prediction modeling for SI across data from all studies, the area under the receiver operating characteristic (AUROC) curve ranged from 0.656 to 0.739. AUROC values ranged from 0.599 to 0.730 in data from phase 3 and 3b/4 studies, and from 0.563 to 0.643 in data from ORAL Surveillance only.ConclusionsBaseline factors associated with SIs in the tofacitinib RA clinical trial program were similar to established SI risk factors associated with advanced treatments for RA. Furthermore, while model performance in predicting SI was similar to other published models, this did not meet the threshold for accurate prediction (AUROC > 0.85). Thus, predicting the occurrence of SIs at baseline remains challenging and may be complicated by the changing disease course of RA over time. Inclusion of other patient-associated and healthcare delivery-related factors and harmonization of the duration of studies included in the models may be required to improve prediction.Trial registrationClinicalTrials.gov: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT02831855; NCT02092467.

Influence of smoking, nutrition and other modifiable environmental factors on rheumatoid arthritis

Numerous reports in recent years have focused on the influence of environmental factors on rheumatoid arthritis. This article provides an overview of the current study situation on the influence of modifiable environmental factors on the development and course of rheumatoid arthritis. Lifestyle factors, such as cigarette smoking, diet, exercise and body weight can be individually influenced. Factors such as air pollution and socioeconomic status can be influenced by environmental and sociopolitical measures at apublic level. Epidemiological studies have identified nicotine abuse, an unhealthy diet and obesity as well as alow level of education and social status as risk factors for the development of rheumatoid arthritis. Numerous factors are also associated with apoorer response to treatment and aworse prognosis. As randomized interventional studies on most environmental factors are hardly feasible, the causal relationship of the individual factors to the incidence and progression of rheumatoid arthritis is difficult to quantify. Nevertheless, the current evidence already enables the provision of appropriate counselling to patients with rheumatoid arthritis with respect to ahealthy lifestyle including abstaining from cigarette smoking, maintaining ahealthy diet, physical activity and avoiding obesity.

Atlantoaxial Instability in the Course of Rheumatoid Arthritis in Relation to Selected Parameters of Sagittal Balance.

Background: Atlantoaxial instability is the most common cervical instability in patients with rheumatoid arthritis (RA). Its course may differ in different patients and may have different degrees of severity and symptoms. Methods: There are a number of studies on systemic factors associated with the development of this instability, but there are few publications in the scientific literature on the influence of biomechanical factors on the development of cervical instability. One of the areas that allows the study of biomechanical factors influencing spine pathologies is the analysis of sagittal balance using radiological parameters. The study of radiological parameters of sagittal balance has contributed to understanding the pathology of selected spine diseases and is currently an indispensable tool in planning surgical treatment. Results: The presented study, conducted on a group of RA patients with cervical instability, was performed to look for a relationship between C1-C2 instability and sagittal balance parameters. Conclusions: Among the examined selected parameters, a statistically relationship between C1-C2 instability and the Cobb angle C1-C7 and OD-HA parameters has been found. This confirms the need for further in-depth research on this areas.

Rheumatoid meningitis sine arthritis: An emerging cause of isolated pachymeningitis and leptomeningitis with typical features

Background and purposeRheumatoid meningitis (RM) is a meningeal inflammation rarely occurring during the course of rheumatoid arthritis (RA). Anti-citrullinated protein antibodies (ACPA), which are highly specific biomarkers of RA, may allow RM sine arthritis (RMSA) to be diagnosed as an extra-articular early lesion of RA. MRI typically displays pachymeningitis and/or leptomeningitis predating convexity, and CSF diffusivity is focally restricted. Blood ACPA is a strong clue and intrathecal synthesis of ACPA is characteristic although rarely reported. MethodsWe report two cases of RMSA that were confirmed by meningeal biopsy and intrathecal synthesis. ResultsRMSA abated after steroids alone or associated with rituximab. No arthritis occurred during the follow-up. ConclusionRM can occur in the absence of RA.

Effect of Surgery for Fungal Sinusitis on the Clinical Course of Rheumatoid Arthritis

Effect of Surgery for Fungal Sinusitis on the Clinical Course of Rheumatoid Arthritis

Investigating the Association of Aortic Stiffness and Phase Angle with the Clinical Course of Rheumatoid Arthritis.

Aortic stiffness is an independent predictor of cardiovascular events which is increased in rheumatoid arthritis (RA). It can be measured by carotid-femoral pulse wave velocity (cfPWV). Phase angle (PhA) is lower in patients with cardiovascular disease and may be informative in assessing the clinical course of RA. In this observational and cross-sectional study, all RA patients referred to the Imam Khomeini Hospital rheumatology clinic between September 2022 and March 2023 were included in the study. RA activity was assessed using the DAS28 criteria. In the patients, PhA and cfPWV were measured using Inbody-s10 and PulsePen tonometer instruments. The relationships between PhA, cfPWV, clinical course of RA, and CRP were evaluated using regression analysis. 53 patients were included in the study (83% female, mean age 46.5 years). Significant inverse relationships existed between PhA, CRP, and age (P value = 0.003, 0.0001, R: 0.69, respectively). People with aortic stiffness had a lower mean PhA (P value = 0.05). In patients with RA duration of less than 10 years, the cfPWV percentile and the prevalence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positive cases were higher than in patients with RA duration >10 years (P values = 0.02, 0.01, respectively). With increasing duration of RA, aortic stiffness and positive serology cases decreased. PhA and cfPWV may be useful in assessing the clinical course of RA to prevent cardiovascular events.

Coexistence of Hashimoto’s thyroiditis, rheumatoid arthritis, Sjogren’s syndrome, and ulcerative colitis

Introduction and importance: The coexistence of Hashimoto’s thyroiditis and ulcerative colitis has been previously mentioned, as these diseases are autoimmune diseases. Limited data about the coexistence of rheumatoid arthritis in patients with Hashimoto’s thyroiditis have been published till now. Meanwhile, the coexistence of Sjogren’s syndrome during the course of rheumatoid arthritis is well known. The coexistence of Hashimoto’s thyroiditis, Sjogren’s syndrome, and ulcerative colitis has also been reported in rare cases. Case presentation: A 32-year-old female, with a 10-year history of Hashimoto’s thyroiditis, 4 years of rheumatoid arthritis, and 2 years of secondary Sjogren’s syndrome, presented to our Rheumatology Department, complaining of fatigue, weight loss, intermittent abdominal pain, and bloody diarrhea for the last 6 weeks. Her colonoscopy findings were compatible with a diagnosis of ulcerative colitis. Clinical discussion: Multiple autoimmune syndromes are defined as the presence of three or more autoimmune diseases in the same patient. They have an increased frequency in patients with a previous history of another autoimmune disease, and a higher correlation with females. The prevalence is rare and was documented only by two systematic reviews, with the rest being separate case reports. Autoimmune thyroid disease and Sjögren’s syndrome were the most frequent diseases encountered, followed by rheumatoid arthritis, and systemic lupus erythematosus. The presence of these autoimmune diseases together suggests that they share a common pathological and physiological genesis. Conclusion: This is the first case report, to our knowledge, that describes the coexistence of Hashimoto’s thyroiditis, rheumatoid arthritis, Sjogren’s syndrome, and ulcerative colitis within 10 years, without a positive family history or psychological stress. Therefore, further studies and long-term surveys are needed to identify other factors that can contribute to the coexistence of these rare diseases.

Hypogonadism in men with inflammatory joint diseases: Frequency and clinical characteristics

To study the frequency of hypogonadism (HG) in men with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to evaluate the impact of HG on the course of RA and and concomitant diseases. A single-stage continuous study included 170 men with RA, 57 men with AS and 85 men with PsA, who were hospitalized at the Nasonova Research Institute of Rheumatology. Patients were assessed for total testosterone (ТS) levels and subsequently divided into subgroups with normal (>12 nmol/l) and reduced levels. An intergroup comparison was carried out on the main indicators used in clinical rheumatological practice to assess the stage, activity and other medical and demographic characteristics of rheumatic disease, as well as on concomitant conditions. The second stage of the study involved a pairwise intergroup comparison among patients with HG with RA, AS and PsA. The incidence of ТS deficiency among patients with RA was 24.1%, among patients with AS - 17.5%, and with PsA - 31.8%. In patients with RA, HG was associated with a significantly higher mean body mass index, higher fasting blood glucose and uric acid, higher erythrocyte sedimentation rate and anemia. Patients with AS with HG had significantly lower hemoglobin levels and more frequent anemia, as well as higher levels of C-reactive protein and erythrocyte sedimentation rate. In PsA, older age was observed in the androgen deficiency group, as well as higher body mass index and fasting glucose levels; obesity was more common. An intergroup comparison of quantitative and qualitative indicators between patients with androgen deficiency in all three rheumatic diseases (RDs) did not reveal significant differences in the average concentrations of ТS, luteinizing hormone, sex hormone binding globulin, experience of RD, laboratory markers of inflammatory activity, as well as glucose and uric acid. A similar incidence of diabetes mellitus, obesity and anemia was noted for all three nosologies. ТS levels and the presence of HG were not associated with the stage and activity of RD, but ТS deficiency was accompanied by higher laboratory indicators of inflammatory activity, lower hemoglobin values, and metabolic disorders. Patients with HG, regardless of nosology, had similar levels of sex hormones and indicators reflecting RD and concomitant conditions.

Causal relationships between circulating metabolites and rheumatoid arthritis: A mendelian randomization study

BackgroundBlood metabolites serve as pivotal indicators in identifying and predicting the course of rheumatoid arthritis (RA). However, empirical substantiation of a direct causal link between these serum biomarkers and the development of RA is still lacking comprehensive support. MethodIn pursuit of a thorough exploration of the causal links between circulating blood metabolites and RA, we deployed a two-sample Mendelian randomization (MR) approach during our initial investigative phase. This method was utilized to examine the potential connections between 249 distinct circulating metabolites and the prevalence of RA. In the validation phase, we conducted replication analyses with a new metabolic dataset consisting of 123 metabolites. Furthermore, we employed the Mendelian randomization based on Bayesian model averaging (MR-BMA) technique to pinpoint key metabolic characteristics that have significant causal implications. ResultsIn our primary analysis, we found that acetate, acetoacetate and pyruvate exhibited a consistent protective causal association with rheumatoid arthritis, while lactate demonstrated a positive correlation with rheumatoid arthritis risk. It is also noteworthy that a substantial subset of traits related to both saturated and unsaturated fatty acids showed causal influences. Subsequent secondary analyses substantiated these observations, revealing that traits associated with the average number of methylene groups in a fatty acid chain exhibited protective effects. Ultimately, our MR-BMA analyses unveiled that the ratio of polyunsaturated fatty acids (PUFAs) to total fatty acids assumes a paramount role in increasing the susceptibility to rheumatoid arthritis. ConclusionsBy employing systemic MR analyses, our study has successfully generated an all-encompassing atlas elucidating the intricate connections between circulating metabolites and the susceptibility to rheumatoid arthritis. Our results indicate the high unsaturation degree is a dominant risk factors correlated with rheumatoid arthritis.

Construction of janus mesenchymal stem cell-hitchhiked melanin nanoparticles to modulate the Th17/Treg balance for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a common chronic inflammatory disease capable of causing the disability. Although various antioxidant strategies have been attempted for prevention and treatment of RA through scavenging the free radicals, the therapeutic effect is limited. Recently, it is reported that the unremitting course of RA intensely correlates with the persistence of immunologic memory, in which the imbalance of T helper 17 (Th17) cells/regulatory T (Treg) cells plays an important role. Herein, we constructed Janus mesenchymal stem cell (MSC)-hitchhiked melanin nanoparticles (MSCFM) for RA therapy, where one half of MSC kept intact for chemotactically migrating towards the RA inflammatory sites and efficiently restoring the Th17/Treg balance based on the property of MSCs, while the other half hitchhiked the iron-doped melanin (FM) nanoparticles (NPs) and release them to scavenge free radicals for maintaining the durability of Th17/Treg balance. In vitro studies indicated MSCFM could migrate towards CXCL12 inflammatory cytokine, scavenge reactive oxygen and nitrogen species, inhibit Th17 cell proliferation and induce Treg cell production. Further in vivo studies corroborated that intravenously injected MSCFM could target the RA site of collagen-induced arthritis mouse model and alleviate the pathological progression of RA. MSCFM holds great potential as an anti-inflammatory agent for RA management.

Ganlu formula ethyl acetate extract (GLEE) blocked the development of experimental arthritis by inhibiting NLRP3 activation and reducing M1 type macrophage polarization

Ethnopharmacological relevanceThe Tibetan medicine Ganlu Formula, as a classic prescription, is widely used across the Qinghai-Tibet Plateau area of China, which has a significant effect on relieving the course of rheumatoid arthritis (RA). However, the active compounds and underlying mechanisms of Ganlu Formula in RA treatment remain largely unexplored. Aim of the studyThis study aimed to elucidate the active substances and potential mechanisms of the ethyl acetate extract of Ganlu Formula ethyl acetate extract (GLEE) in the treatment of RA. Materials and methodsUltra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was utilized to analyze and identify the chemical constituents within GLEE. Discovery Studio molecular virtual docking technology was utilized to dock the interaction of GLEE with inflammation-related pathway proteins. The GLEE gene library was obtained by transcriptome sequencing. Collagen-induced arthritic（CIA) rats were utilized to assess the antiarthritic efficacy of GLEE. Micro-CT imaging was employed to visualize the rat paw, and ultrasound imaging revealed knee joint effusion. Evaluation of synovial tissue pathological changes was conducted through hematoxylin-eosin staining and saffranine solid green staining, while immunohistochemical staining was employed to assess NLRP3 expression along with inflammatory markers. Immunofluorescence staining was utilized to identify M1 macrophages. ResultsMetabolomic analysis via UPLC-Q-TOF-MS identified 28 potentially bioactive compounds in GLEE, which interacted with the active sites of key proteins such as NLRP3, NF-κB, and STAT3 through hydrogen bonds, C–H bonds, and electrostatic attractions. In vitro analyses demonstrated that GLEE significantly attenuated NLRP3 inflammasome activation and inhibited the polarization of bone marrow-derived macrophages (BMDMs) towards the M1 phenotype. In vivo, GLEE not only prevented bone mineral density (BMD) loss but also reduced ankle swelling in CIA rats. Furthermore, it decreased the expression of the NLRP3 inflammasome and curtailed the release of inflammatory mediators within the knee joint. ConclusionGLEE effectively mitigated inflammatory responses in both blood and knee synovial membranes of CIA rats, potentially through the down-regulation of the NLRP3/Caspase-1/IL-1β signaling pathway and reduction in M1 macrophage polarization.

The changes of intestinal flora and its relevance with memory Tfh and B cells in rheumatoid arthritis patients treated with csDMARDs and csDMARDs + bDMARDs

BackgroundA growing body of experimental and clinical evidence has implicated gut microbiota in the onset and course of rheumatoid arthritis (RA). The imbalance of intestinal flora in RA patients may lead to abnormal expression of immune cells and related cytokines. PurposeConventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and conventional synthetic disease-modifying antirheumatic drugs combined with biological disease-modifying antirheumatic drugs (csDMARDs + bDMARDs) are widely used to treat RA, but the characteristics of gut microbiota before and after treatment and their relationship with memory Tfh/B cells and cytokines remain unclear. MethodsStool samples were collected from 50 RA patients and 25 healthy controls (HCs) for 16SrRNA gene sequencing. We examined the proportion of lymphocyte subsets in healthy controls and RA patients. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of related cytokines in serum. The α and β diversity of intestinal flora, and the correlation between intestinal flora and clinical indicators, lymphocyte subsets, cytokines were analyzed. ResultAt the genus level, Ruminococcaceae_Ruminococcus was decreased in the csDMARDs and csDMARDs + bDMARDs treatment group, whereas Faecalibacterium was reduced in the csDMARDs treatment group, compared to untreated group. CD4+CD45RO+CCR7+CXCR5+central memory Tfh cells and CD4+CD45RO+CCR7-CXCR5+effector memory Tfh cells were significantly lower in the csDMARDs + bDMARDs treatment group than in untreated group. CD19+CD27+IgD+pre-switched memory B cells were higher in the csDMARDs and csDMARDs + bDMARDs treatment groups, whereas CD19+CD27+IgD-switched memory B cells were significantly lower than in untreated group. Ruminococcaceae_Ruminococcus was negatively correlated with CD19+CD27+IgD+ pre-switched memory B cells but positively correlated with CD4+CD45RO+CCR7-CXCR5+effector memory Tfh and CD19+CD27+IgD-switched memory B cells in patients with RA treated with DMARDs. ConclusionThe gut microbiota, memory Tfh cells, memory B cells, and cytokines of patients with RA changed significantly under different treatment regimens and had certain correlations with the clinical indicators of RA.

Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines.

Rheumatoid arthritis (RA) is recognized as an autoimmune joint disease driven by T cell responses to self (or modified self or microbial mimic) antigens that trigger and aggravate the inflammatory condition. Newer treatments of RA employ monoclonal antibodies or recombinant receptors against cytokines or immune cell receptors as well as small-molecule Janus kinase (JAK) inhibitors to systemically ablate the cytokine or cellular responses that fuel inflammation. Unlike these treatments, a therapeutic vaccine, such as CEL-4000, helps balance adaptive immune homeostasis by promoting antigen-specific regulatory rather than inflammatory responses, and hence modulates the immunopathological course of RA. In this review, we discuss the current and proposed therapeutic products for RA, with an emphasis on antigen-specific therapeutic vaccine approaches to the treatment of the disease. As an example, we describe published results of the beneficial effects of CEL-4000 vaccine on animal models of RA. We also make a recommendation for the design of appropriate clinical studies for these newest therapeutic approaches, using the CEL-4000 vaccine as an example. Unlike vaccines that create or boost a new immune response, the clinical success of an immunomodulatory therapeutic vaccine for RA lies in its ability to redirect autoreactive pro-inflammatory memory T cells towards rebalancing the "runaway" immune/inflammatory responses that characterize the disease. Human trials of such a therapy will require alternative approaches in clinical trial design and implementation for determining safety, toxicity, and efficacy. These approaches include adaptive design (such as the Bayesian optimal design (BOIN), currently employed in oncological clinical studies), and the use of disease-related biomarkers as indicators of treatment success.

Features of gynecological status and concomitant morbidity in menopausal women with resistant rheumatoid arthritis and obesity

Oftentimes, women with RA experience remission during pregnancy. The beneficial effect of pregnancy on the RA course is associated with a specific hormonal status, including high levels of estriol and progesterone that have known anti-inflammatory effects. After childbirth, decreased endogenous production of steroids can trigger the onset or exacerbation of RA.Objective. Studying of the characteristics of the gynecological status and concomitant extragenital diseases in postmenopausal women with rheumatoid arthritis (RA) depending on the presence of obesity.Materials and methods. 394 postmenopausal women with RA (diagnosed according to ACR/EULAR 2010 criteria) were included. By decision of the medical commission, all patients were approved for therapy with genetically engineered biological drugs and/or JAK kinase inhibitors. Before inclusion in the study, all patients had a detailed medical history, an allergic history, registered comorbidities, and a physical and laboratory-instrumental examination. Depending on the BMI values, the study participants were divided into groups. Group A included 103 obese patients of any severity (BMI ≥ 30 kg/m2). Group B included 291 women with BMI <30 kg/m2. Patients with an inflammatory process were found to have groups of inflammation by age and duration of RA (p > 0.05).Results. In patients of group A, more often than in patients of group B, comorbidities were detected: hypertension (p < 0.0001), coronary heart disease (p = 0.03), history of “vascular accidents” (p = 0.0009), especially acute cerebrovascular accident (p = 0.004), type 2 diabetes mellitus (p = 0.0005), which manifest themselves over the age of 45, that is, during the perimenopause. When correcting the gynecological history data, he draws attention to the fact that group A patients are more likely to operate surgically and on the pelvic organs: more had the uterus removed (p = 0.002) or ovarian resection was performed (p < 0.0001), and the frequency of surgical menopause in group A was higher than in group B (p = 0.0009). The debut of RA on average chronologically coincided with the onset of menopause (p = 0.01). At the same time, in the average age of the onset of menopause, it is rare (p > 0.05). The number of women who had a history of pregnancy, childbirth, miscarriages and abortions in the groups were repeated (p > 0.05). But in group A, the average number of pregnancies (p = 0.003) and abortions (p = 0.004) per woman was higher than in group B.Conclusion. The results of the study revealed the identification of clinical manifestations of inflammation and the severity of rheumatoid arthritis, depending on the presence of concomitant obesity in postmenopausal women, as well as a rarer occurrence of osteoporosis in women with RA and concomitant obesity.

Rheumatoid arthritis - medication dosage in chronic kidney disease.

Renal failure in the course of rheumatoid arthritis (RA) is a consequence of many factors, including drug-induced nephrotoxicity, comorbidities and chronic inflammation. Contemporary treatment strategies have reduced the incidence of renal failure in the population of RA patients. However, it remains a problem for approximately 25% of patients. Therefore, special attention should be paid to the potential need for dosage modifications of administered medications. Many drugs used in the therapy of rheumatic diseases have not been thoroughly studied for their safety in patients with reduced glomerular filtration, resulting in limited data in this area. The establishment of precise, transparent, and consistent dosage recommendations for antirheumatic drugs in chronic kidney disease would significantly facilitate the care of patients with RA. The following review provides a general summary of the available knowledge regarding the dosage of rheumatic medications in renal insufficiency and aims to highlight the need for further research in this area.