Vasculitis reumatoidea: una manifestación poco habitual. Presentación de tres casos clínicos y revisión de la literatura

La vasculitis reumatoidea es una complicación sistémica y poco frecuente de la Artritis Reumatoidea. Si bien su incidencia ha descendido en los últimos años con el advenimiento de las nuevas terapias inmunosupresoras y biológicas, continua teniendo una alta morbimortalidad. Predomina en el sexo masculino, en pacientes seropositivos y con un largo período de la enfermedad establecida. Requiere de alta presunción diagnostica, siendo el compromiso cutáneo y nervioso periférico el más frecuente. La biopsia de nervio o piel es requerida habitualmente para su diagnóstico. El tratamiento se basa en corticoides e inmunosupresores. Presentamos tres casos clínicos y realizamos una revisión de la literatura.

Rheumatoid vasculitis is a rare systemic complication of rheumatoid arthritis. Although its incidence has decreased in recent years with the advent of new immunosuppressive and biological therapies, it continues to have a high morbidity and mortality. It predominates in males, in seropositive patients and with a long period of established disease. It requires high diagnostic presumption, with skin and peripheral nervous involvement being the most affected. Nerve or skin biopsy is usually required for diagnosis. Treatment is based on corticosteroids and immunosuppressants. We present three clinical cases and carry out a review of the literature.

A vasculite reumatóide é uma complicação sistêmica rara da artrite reumatóide. Embora sua incidência tenha diminuído nos últimos anos com o advento de novas terapias imunossupressoras e biológicas, continua apresentando elevada morbidade e mortalidade. Predomina no sexo masculino, em pacientes soropositivos e com longo período de doença estabelecida. Exige alta presunção diagnóstica, sendo o envolvimento cutâneo e nervoso periférico os mais afetados. A biópsia de nervo ou pele geralmente é necessária para o diagnóstico. O tratamento é baseado em corticosteroides e imunossupressores. Apresentamos três casos clínicos e realizamos uma revisão da literatura.

Sinomenine treats rheumatoid arthritis by inhibiting MMP9 and inflammatory cytokines expression: bioinformatics analysis and experimental validation.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease marked by inflammatory cell infiltration and joint damage. The Chinese government has approved the prescription medication sinomenine (SIN), an effective anti-inflammation drug, for treating RA. This study evaluated the possible anti-inflammatory actions of SIN in RA based on bioinformatics analysis and experiments. Six microarray datasets were acquired from the gene expression omnibus (GEO) database. We used R software to identify differentially expressed genes (DEGs) and perform function evaluations. The CIBERSORT was used to calculate the abundance of 22 infiltrating immune cells. The weighted gene co-expression network analysis (WGCNA) was used to discover genes associated with M1 macrophages. Four public datasets were used to predict the genes of SIN. Following that, function enrichment analysis for hub genes was performed. The cytoHubba and least absolute shrinkage and selection operator (LASSO) were employed to select hub genes, and their diagnostic effectiveness was predicted using the receiver operator characteristic (ROC) curve. Molecular docking was undertaken to confirm the affinity between the SIN and hub gene. Furthermore, the therapeutic efficacy of SIN was validated in LPS-induced RAW264.7 cells line using Western blot and Enzyme-linked immunosorbent assay (ELISA). The matrix metalloproteinase 9 (MMP9) was identified as the hub M1 macrophages-related biomarker in RA using bioinformatic analysis and molecular docking. Our study indicated that MMP9 took part in IL-17 and TNF signaling pathways. Furthermore, we found that SIN suppresses the MMP9 protein overexpression and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the LPS-induced RAW264.7 cell line. In conclusion, our work sheds new light on the pathophysiology of RA and identifies MMP9 as a possible RA key gene. In conclusion, the above findings demonstrate that SIN, from an emerging research perspective, might be a potential cost-effective anti-inflammatory medication for treating RA.

Risk for cardiovascular disease development in rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis have significant cardiovascular mortality and morbidity. OBJECTIVE: To 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. METHODS: A 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. RESULTS: The 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. CONCLUSION: A 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.

Large stokes shift and near-infrared fluorescent probe for bioimaging and evaluating the HClO in an rheumatoid arthritis mouse model.

It is crucial to identify aberrant HClO levels in living things since they pose a major health risk and are a frequent reactive oxygen species (ROS) in living organisms. In order to detect HClO in various biological systems, we created and synthesized a near-infrared fluorescent probe with an oxime group (-C = N-OH) as a recognition unit. The probe DCMP1 has the advantages of fast response (10 min), near-infrared emission (660 nm), large Stokes shift (170 nm) and high selectivity. This probe DCMP1 not only detects endogenous HClO in living cells, but also enables further fluorescence detection of HClO in living zebrafish. More importantly, it can also be used for fluorescence imaging of HClO in an rheumatoid arthritis mouse model. This fluorescent probe DCMP1 is anticipated to be an effective tool for researching HClO.

Association Between Rheumatoid Arthritis and Clonal Hematopoiesis: A Mendelian Randomization Study.

Immunity activation and inflammation are the main characteristics of rheumatoid arthritis and clonal hematopoiesis. However, it remains unclear whether rheumatoid arthritis increase the risk of clonal hematopoiesis. Here, a Mendelian randomization (MR) analysis was conduct to explore the causal effects of rheumatoid arthritis on clonal hematopoiesis. Summary statistics data of rheumatoid arthritis (13,838 cases and 33,742 controls) and clonal hematopoiesis (10,203 cases and 173,918 controls) derived from a genomewide association study were selected to analyze. We selected inverse-variance weighted, MR-Egger, weighted median, simple mode, and weighted mode to evaluate the causal effect of rheumatoid arthritis on clonal hematopoiesis. The two-sample MR analysis suggested a strong causal relationship between rheumatoid arthritis and clonal hematopoiesis by inverse-variance weighted (OR = 1.002311673, 95% CI [1.000110757, 1.004517433], p = .039706) and weighted median (OR = 1.002311673, 95% CI [1.000110757, 1.004517433], p = .039518447) methods. No significant pleiotropy or heterogeneity was found in the sensitivity analysis. These results supported a potentially causal relationship between rheumatoid arthritis and clonal hematopoiesis, and the exposure of rheumatoid arthritis increased the risks of clonal hematopoiesis. Our findings highlight the importance of how chronic inflammation and immune activation induced rheumatoid arthritis enhances the risks of clonal hematopoiesis, and that early intervention with rheumatoid arthritis patients might reduce the clonal hematopoiesis risks in rheumatoid arthritis patients. Moreover, our study provides clues for prediction of risk factors and potential mechanisms of clonal hematopoiesis.

Factors associated with change in arterial stiffness in patients with rheumatoid arthritis: the JointHeart study.

BACKGROUND: Rheumatoid arthritis (RA) predominantly affects women and is associated with hypertension and arterial stiffness. We explored factors associated with change in arterial stiffness in patients with RA treated with disease-modifying antirheumatic drug (DMARD) therapy. METHODS: Seventy-seven outpatients with RA (age 55 ± 11, 69% women), with indication for treatment with biological or targeted synthetic DMARDs, were included. Pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx) and Disease Activity Score in 28 joints (DAS28) were measured at baseline and after a mean of 22 months of follow-up. RESULTS: At follow-up, 83% used DMARDs and 73% had achieved remission or low disease activity. DAS28 decreased from 3.8 ± 1.3 to 2.8 ± 1.2 (p < 0.001). Mean PWV increased from 7.8 ± 1.6 m/s at baseline to 8.5 ± 1.8 m/s at follow-up (p < 0.001), while AP and AIx were stable. Increase in PWV during follow-up was associated with increase in systolic blood pressure (BP), diabetes, higher DAS28 and body mass index (BMI) at baseline, independent of achieved remission/low disease activity and use of DMARDs at follow-up. In multivariable analyses at follow-up, female sex was associated with higher AP and AIx, but with lower PWV, after adjusting for possible confounders. CONCLUSION: In patients with RA, higher disease activity, BMI and diabetes at baseline, together with increase in office systolic BP were associated with an increase in arterial stiffness during follow-up, despite DMARD therapy. This highlights the need for management of cardiovascular risk factors in addition to reducing the inflammatory load in patients with RA to preserve arterial function.

Rheumatoid arthritis (RA) affects women more often than men and leads to chronic inflammation and faster stiffening of the arteries. In this study, we identified factors that were associated with increase in arterial stiffness during 22 months of follow-up in patients with RA treated with modern antirheumatic medication.This study included 77 patients with RA (69% women), that were in need of change in their disease-modifying antirheumatic medication.We measured arterial stiffness at baseline and repeated it after 22 months of follow-up.At follow-up, arterial stiffness had increased while the disease activity had improved. The rise in arterial stiffness was associated with having diabetes, higher body mass index and higher disease activity at the start of the study and with experiencing an increase in blood pressure during follow-up.This study highlights the need for maintaining a healthy lifestyle and treating cardiovascular risk factors like blood pressure and obesity in patients with RA beyond using modern antirheumatic medication to avoid stiffening of the arteries.

PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide-isomerase A3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein (CRP) level and disease activity score 28 (DAS28). Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor (TCR) signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing Th1 and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

The immunomodulatory of interleukin-33 in rheumatoid arthritis: A systematic review.

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that primarily affects the joints and surrounding soft tissues, characterized by chronic inflammation and proliferation of the synovium. Various immune cells are involved in the pathophysiology of RA. The complex interplay of factors such as chronic inflammation, genetic susceptibility, dysregulation of serum antibody levels, among others, contribute to the complexity of the disease mechanism, disease activity, and treatment of RA. Recently, the cytokine storm leading to increased disease activity in RA has gained significant attention. Interleukin-33 (IL-33), a member of the IL-1 family, plays a crucial role in inflammation and immune regulation. ST2 (suppression of tumorigenicity 2 receptor), the receptor for IL-33, is widely expressed on the surface of various immune cells. When IL-33 binds to its receptor ST2, it activates downstream signaling pathways to exert immunoregulatory effects. In RA, IL-33 regulates the progression of the disease by modulating immune cells such as circulating monocytes, tissue-resident macrophages, synovial fibroblasts, mast cells, dendritic cells, neutrophils, T cells, B cells, endothelial cells, and others. We have summarized and analyzed these findings to elucidate the pathways through which IL-33 regulates RA. Furthermore, IL-33 has been detected in the synovium, serum, and synovial fluid of RA patients. Due to inconsistent research results, we conducted a meta-analysis on the association between serum IL-33, synovial fluid IL-33, and the risk of developing RA in patients. The pooled SMD was 1.29 (95% CI: 1.15-1.44), indicating that IL-33 promotes the onset and pathophysiological progression of RA. Therefore, IL-33 may serve as a biomarker for predicting the risk of developing RA and treatment outcomes. As existing drugs for RA still cannot address drug resistance in some patients, new therapeutic approaches are needed to alleviate the significant burden on RA patients and healthcare systems. In light of this, we analyzed the potential of targeting the IL-33/ST2-related signaling pathway to modulate immune cells associated with RA and alleviate inflammation. We also reviewed IL-33 and RA susceptibility-related single nucleotide polymorphisms, suggesting potential involvement of IL-33 and macrophage-related drug-resistant genes in RA resistance therapy. Our review elucidates the role of IL-33 in the pathophysiology of RA, offering new insights for the treatment of RA.

An effective LC-MS method for the simultaneous determination of a potential anti-rheumatoid arthritis drug, carboxyamidotriazole, and its major metabolite in rat plasma.

Carboxyamidotriazole (CAI) was previously recognized as a well-tolerated anticancer drug. It has also demonstrated significant anti-inflammatory effects in various cell and animal model experiments, prompting its investigation as a potential treatment for rheumatoid arthritis. In this study, the potential biotransformation metabolites of CAI were identified both in vitro and in vivo. A sensitive, specific, and accurate LC-MS method was developed for the quantitative analysis of CAI and its major metabolite, CAI-OH, in rat plasma. CAI, CAI-OH, and telmisartan (used as an internal standard) were separated using a Zorbax SB C18 column. The mobile phase consisted of water (phase A, containing 0.1% formic acid) and acetonitrile (phase B, containing 0.1% formic acid) at a flow rate of 0.2 mL/min. The analytes were examined using a high-resolution mass spectrometer, with detected mass-to-charge ratios of m/z 424.01293 for CAI, m/z 440.00785 for CAI-OH, and m/z 515.24415 for telmisartan. Good linearity was observed within the range of 10-5000 ng/mL. Both inter- and intra-batch precision (relative standard deviation, %) were below 6%, and the accuracy ranged from 94.9% to 106.1%. The analytes remained stable throughout the entire experimental period. This method was successfully applied in a pharmacokinetic study of CAI following oral administration in rats.

Prevalence and Characteristics of Adults with Difficult-to-Treat Rheumatoid Arthritis in a Large Patient Registry.

OBJECTIVES: An estimated 5-20% of patients with rheumatoid arthritis (RA) fail multiple treatments and are considered "difficult-to-treat" (D2T), posing a substantial clinical challenge for rheumatologists. A European Alliance of Associations for Rheumatology (EULAR) task force proposed a definition of D2T-RA in 2021. We applied EULAR's D2T definition in a cohort of patients with established RA to assess prevalence and we compared clinical characteristics of participants with D2T-RA with matched comparisons. METHODS: Data from the longitudinal Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry was used. Participants were classified as D2T if they met EULAR's definition. A comparison group of non-D2T RA patients were matched 2:1 to every D2T patient, and differences in characteristics were evaluated in descriptive analyses. Prevalence rates of D2T were estimated using Poisson regression. RESULTS: We estimated the prevalence of D2T-RA to be 14.4 (95% CI: 12.8-16.3 per 100 persons) among 1,581 participants with RA, and 22.3 (95% CI: 19.9-25.0 per 100 persons) among 1,021 who were biologic/targeted synthetic DMARD experienced. We observed several differences in demographics, comorbidities, and RA disease activity between D2T-RA and non-D2T RA comparisons. Varying EULAR sub-criteria among all participants in BRASS resulted in a range of D2T-RA prevalence rates, from 0.6-17.5 per 100 persons. CONCLUSION: EULAR's proposed definition of D2T-RA identifies patients with RA who have not achieved treatment targets. Future research should explore heterogeneity in these patients and evaluate outcomes to inform the design of future studies aimed at developing more effective RA management protocols.

The antiangiogenic effect of total saponins of Panax japonicus C.A. Meyer in rheumatoid arthritis is mediated by targeting the HIF-1α/VEGF/ANG-1 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese herbal medicine Panax japonicus C.A. Meyer has a long history in clinical treatment of rheumatoid arthritis (RA). Total saponins of Panax japonicus C.A. Meyer (TSPJs) were extracted from the root of Panax japonicus C.A. Meyer, and its anti-rheumatism mechanism is still unclear. AIM OF THE STUDY: To investigate whether TSPJs attenuated synovial angiogenesis in RA and explore the potential mechanisms. MATERIALS AND METHODS: Potential TSPJs targets involving gene function were predicted by network pharmacology related databases. Bioinformatics analysis and molecular docking technology were used to predict the mechanism of TSPJs in the treatment of RA. The predicted results were validated by cell experiments and a collagen-induced arthritis (CIA) mouse model. RESULTS: Bioinformatics analysis results showed that TSPJs may inhibit RA-related angiogenesis through the hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) pathways. In vitro, different doses of TSPJs showed a good inhibitory effect on the tube formation of EA.hy926 cells. The results of the cellular thermal shift assay indicated that TSPJs can bind to the HIF-1α, VEGFA, and angiopoietin-1 (ANG-1) proteins. In vivo, the administration of TSPJs alleviated the symptoms of CIA mice, including the arthritis index, hind paw thickness, and swollen joint count. The histological results demonstrated that TSPJs inhibited inflammation, angiogenesis, bone damage, and cartilage destruction. Furthermore, TSPJs decreased the number of vessels and the expression level of CD31. The mechanistic results revealed that TSPJs decreased the expression of HIF-1α, VEGFA, and ANG-1 in the serum or synovial tissues of CIA mice. CONCLUSION: These results suggest that TSPJs effectively inhibit angiogenesis in RA, and the mechanism may be related to inhibiting the HIF-1α/VEGF/ANG-1 axis.

Global pattern, trend, and cross-country inequality of early musculoskeletal disorders from 1990 to 2019, with projection from 2020 to 2050.

BACKGROUND: This study aims to estimate the burden, trends, forecasts, and disparities of early musculoskeletal (MSK) disorders among individuals ages 15 to 39 years. METHODS: The global prevalence, years lived with disabilities (YLDs), disability-adjusted life years (DALYs), projection, and inequality were estimated for early MSK diseases, including rheumatoid arthritis (RA), osteoarthritis (OA), low back pain (LBP), neck pain (NP), gout, and other MSK diseases (OMSKDs). FINDINGS: More adolescents and young adults were expected to develop MSK disorders by 2050. Across five age groups, the rates of prevalence, YLDs, and DALYs for RA, NP, LBP, gout, and OMSKDs sharply increased from ages 15-19 to 35-39; however, these were negligible for OA before age 30 but increased notably at ages 30-34, rising at least 6-fold by 35-39. The disease burden of gout, LBP, and OA attributable to high BMI and gout attributable to kidney dysfunction increased, while the contribution of smoking to LBP and RA and occupational ergonomic factors to LBP decreased. Between 1990 and 2019, the slope index of inequality increased for six MSK disorders, and the relative concentration index increased for gout, NP, OA, and OMSKDs but decreased for LBP and RA. CONCLUSIONS: Multilevel interventions should be initiated to prevent disease burden related to RA, NP, LBP, gout, and OMSKDs among individuals ages 15-19 and to OA among individuals ages 30-34 to tightly control high BMI and kidney dysfunction. FUNDING: The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation. The project is funded by the Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).

Robotic Pills as Innovative Personalized Medicine Tools: A Mini Review.

The most common route for drug administration is the oral route due to the various advantages offered by this route, such as ease of administration, controlled and sustained drug delivery, convenience, and non-invasiveness. In spite of this, oral drug absorption faces challenges due to various issues related to its stability, permeability and solubility in the GI tract. Biologic drugs generally face problems when administered by oral route as they are readily degradable and thus required to be injected. To overcome these issues in oral absorption, different approaches like novel drug delivery systems and newer pharmaceutical technologies have been adopted. With a combined knowledge of drug delivery and pharmaceutical technology, robotic pills can be designed and used successfully to enhance the adhesion and permeation of drugs through the mucus membrane of the GI tract to achieve drug delivery at the target site. The potential application of robotic pills in diagnosis and drug dispensing is also discussed. The review highlights recent developments in robotic pill drug-device technology and discusses its potential applications to solve the problems and challenges in oral drug delivery.

Serum levels of tumour necrosis factor (TNF-α) and interleukin-17 (IL-17) in patients with nail psoriasis: A cross-sectional study.

Background Psoriasis is a common chronic inflammatory disorder affecting all aspects of a patient's life. Nail involvement is frequent, but little is known about its associated inflammatory biomarker profile, including similarities or differences from cutaneous disease. Aims We conducted this cross-sectional study to evaluate serum levels of inflammatory cytokines [tumour necrosis factor-alpha (TNF-α) and interleukin -17 (IL-17)] in patients with nail psoriasis and compared these to psoriasis patients without nail involvement, as well as in non-psoriatic healthy controls. Methods Adult psoriasis patients with (Group I, n = 30) and without nail involvement (Group-II, n = 30) were sequentially recruited. In addition, non-psoriatic healthy controls (Group-III, n = 20) were recruited. The nail disease severity by NAPSI score was determined for patients in Group I. Cutaneous disease severity (by PASI score) and presence of psoriatic arthritis (through CASPAR criteria) were evaluated for patients in Groups I and II. Serum levels of TNF-α, IL-17, erythrocyte sedimentation rate (ESR), rheumatoid factor (RA factor), and anti-cyclic citrullinated peptide antibody (Anti-CCP) were evaluated for all three groups. Results The median age was significantly higher for Group I as compared to Group II patients (41 ± 12.6 years vs 30 ± 12.4 years, p = 0.017). Group I patients also had higher median PASI score than Group II patients, although the difference was not statistically significant (10 ± 11.41 vs 6.50 ± 5.46, p = 0.275). The mean serum IL-17 levels were significantly higher for Group-I (113.39 ± 251.30 pg/mL) than Group II (27.91 ± 18.22 pg/mL, p = 0.002) and Group III (25.67 ± 12.08 pg/mL, p = 0.005). A weak positive correlation was found between NAPSI and serum IL-17 levels (Spearman's Rho = 0.355) though not statistically significant (p = 0.054). Correlation between serum IL-17 and PASI was poor for Group-I patients (Spearman's Rho = 0.13, p = 0.944) and strongly negative for Group-II patients (Spearman's Rho = -0.368, statistically significant with p = 0.045). The mean serum levels of TNF-α were below the detection threshold of the assay kit, hence no meaningful comparison could be made. Limitations A small sample size and low sensitivity of TNF-α assay kit. Conclusion Our study showed that nail psoriasis could be independently associated with an elevation of IL-17. This can help choose appropriate drugs and estimate drug response in patients with nail psoriasis.

Case Report: Effective management of adalimumab-induced acquired hemophilia A with the CyDRI protocol.

Introduction: Acquired Hemophilia A (AHA) is a rare autoimmune disorder characterized by the emergence of inhibitors that specifically target coagulation Factor VIII, frequently resulting in severe bleeding episodes. Methods: We conducted a retrospective analysis of the medical records of a 68-year-old male patient who presented with adalimumab-induced AHA. Results: The patient received adalimumab, a tumor necrosis factor inhibitor antibody, as part of his treatment for rheumatoid arthritis. The patient's clinical journey, characterized by intense bleeding and coagulopathy, was effectively managed with the application of recombinant Factor VIIa (rFVIIa) and the CyDRi protocol. Discussion: The case emphasizes the importance of prompt coagulation assessment in patients with bleeding symptoms receiving disease-modifying therapy for rheumatoid arthritis that includes adalimumab therapy, considering the rare yet life-threatening nature of AHA. Additionally, this report provides an extensive review of the existing literature on drug-induced AHA, with a special emphasis on cases linked to immunomodulatory medications. Through this two-pronged approach, our report aims to enhance understanding and awareness of this severe complication among healthcare providers, promoting timely diagnosis and intervention.

Unraveling the gut microbiota's role in Rheumatoid arthritis: dietary pathways to modulation and therapeutic potential.

Rheumatoid arthritis (RA) is a significant global health issue. Recent research highlights the gut microbiota's critical role in RA's development, noting how dietary factors can alter these microbial communities. This has led to an increased focus on how the gut microbiota (GM) influences RA and the potential for dietary ingredients to offer anti-RA benefits by modifying GM. This review presents a concise examination of the GM associated with RA, identifying specific microbial taxa at various levels that are implicated in the disease. It delves into dietary components known for their anti-RA properties through GM modulation and their mechanisms. Findings from numerous studies, including both animal and human research, show significant differences in the GM composition between individuals with early and established RA. Certain microbes like Tenericutes, Synergistetes, and Proteobacteria have been linked to RA progression, whereas Bacteroidetes and some strains of Lactobacillus are shown to have protective effects against RA. Dietary elements such as fibers, polysaccharides, resistant starch, and peptides have been identified as influential in combating RA. These components work by altering the GM's metabolites and impacting immune cells related to the GM. This review suggests the potential for developing functional foods aimed at treating RA by targeting GM.

Nanomaterials in the Treatment and Diagnosis of Rheumatoid Arthritis: Advanced Approaches.

Rheumatoid arthritis (RA), a chronic inflammatory condition that affects persons between the ages of 20 and 40, causes synovium inflammation, cartilage loss, and joint discomfort as some of its symptoms. Diagnostic techniques for RA have traditionally been split into two main categories: imaging and serological tests. However, significant issues are associated with both of these methods. Imaging methods are costly and only helpful in people with obvious symptoms, while serological assays are time-consuming and require specialist knowledge. The drawbacks of these traditional techniques have led to the development of novel diagnostic approaches. The unique properties of nanomaterials make them well-suited as biosensors. Their compact dimensions are frequently cited for their outstanding performance, and their positive impact on the signal-to-noise ratio accounts for their capacity to detect biomarkers at low detection limits, with excellent repeatability and a robust dynamic range. In this review, we discuss the use of nanomaterials in RA theranostics. Scientists have recently synthesized, characterized, and modified nanomaterials and biomarkers commonly used to enhance RA diagnosis and therapy capabilities. We hope to provide scientists with the promising potential that nanomaterials hold for future theranostics and offer suggestions on further improving nanomaterials as biosensors, particularly for detecting autoimmune disorders.

A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis.

BACKGROUND: The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF­06835375, a potent selective afucosyl immunoglobulin G1 antibody targeting C-X-C chemokine receptor type 5 (CXCR5) that potentially depletes B cells, follicular T helper (Tfh) cells, and circulating Tfh-like (cTfh) cells, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: This first-in-human, multicenter, double-blind, sponsor-open, placebo-controlled Phase 1 study recruited patients aged 18-70 years with SLE or RA. In Part A, patients received single doses of intravenous PF-06835375 (dose range: 0.03-6 mg) or placebo in six sequential single ascending dose (SAD) cohorts. In Part B, patients received repeat doses of subcutaneous PF-06835375 (dose range: 0.3-10 mg) or placebo on Days 1 and 29 in five multiple ascending dose (MAD) cohorts. Tetanus/Diphtheria (Td) and Meningococcal B (MenB/Trumenba™) vaccines were administered at Day 4 (Td and MenB) and Week 8 (MenB only) to assess PF-06835375 functional effects. Endpoints included treatment-emergent adverse events (TEAEs), pharmacokinetic parameters, pharmacodynamic effects on B and cTfh cells, and biomarker counts, vaccine response, and exploratory differential gene expression analysis. Safety, pharmacokinetic, and pharmacodynamic endpoints are summarized descriptively. The change from baseline of B and Tfh cell-specific genes over time was calculated using a prespecified mixed-effects model, with a false discovery rate < 0.05 considered statistically significant. RESULTS: In total, 73 patients were treated (SAD cohorts: SLE, n = 17; RA, n = 14; MAD cohorts: SLE, n = 22; RA, n = 20). Mean age was 53.3 years. Sixty-two (84.9%) patients experienced TEAEs (placebo n = 17; PF-06835375 n = 45); most were mild or moderate. Three (9.7%) patients experienced serious adverse events. Mean t1/2 ranged from 3.4-121.4 h (SAD cohorts) and 162.0-234.0 h (MAD cohorts, Day 29). B and cTfh cell counts generally showed dose-dependent reductions across cohorts (range of mean maximum depletion: 67.3-99.3%/62.4-98.7% [SAD] and 91.1-99.6%/89.5-98.1% [MAD], respectively). B cell-related genes and pathways were significantly downregulated in patients treated with PF-06835375. CONCLUSIONS: These data support further development of PF-06835375 to assess the clinical potential for B and Tfh cell depletion as a treatment for autoimmune diseases. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03334851.