Chronic Autoimmune Disease Research Articles

New therapies in celiac disease.

Celiac disease (CeD) is a chronic autoimmune disorder of the small intestine triggered by gluten ingestion in genetically predisposed individuals. The cornerstone of CeD management remains a strict adherence to a lifelong gluten-free diet (GFD), although such a dietary restriction can lead to an altered quality of life and may not be easy to follow for many patients. These challenges highlighted the need for alternative therapies. This review aims to explore the latest advancements in these therapeutic avenues, emphasizing mechanisms of action, clinical efficacy, and safety profiles of drugs currently in advanced stages of clinical testing. Recent advances in the understanding of CeD pathophysiology have catalyzed the development of new therapeutic approaches, which include strategies to modify gluten processing in the gut, block gluten-triggered immune responses, or restore immune tolerance to gluten. While these therapies are not poised to take the place of GFD, they represent promising treatment alternatives that could enhance the quality of life and minimize long-term consequences in CeD patients. Further research, as well as phase III clinical trials of those already conducted, are needed to establish the feasibility of integrating these novel drugs in the clinical management of CeD.

Dual Targeting Biomimetic Carrier-Free Nanosystems for Photo-Chemotherapy of Rheumatoid Arthritis via Macrophage Apoptosis and Re-Polarization.

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease that often results in irreversible joint erosion and disability. Methotrexate (MTX) is the first-line drug against RA, but the significant side effects of long-term administration limit its use. Therefore, new therapeutic strategies are needed for treating RA. Here, dual-targeting biomimetic carrier-free nanomaterials (BSA-MTX-CyI nanosystem, BMC) is developed for synergistic photo-chemotherapy of RA. Bovine serum albumin (BSA), which has high affinity with SPARC (secreted protein acidic and rich in cysteine) in the RA joint microenvironment, is selected as the hydrophilic end and coupled with MTX and the phototherapeutic agent CyI to self-assemble into BMC. In vitro and in vivo experiments revealed that BMC accumulated significantly at the joint site in collagen antibody-induced arthritis mice and could be specifically recognized and taken up by folate receptors in proinflammatory M1 macrophages. Upon near-infrared laser irradiation, CyI exerted photodynamic and photothermal effects, whereas MTX not only inhibited cell proliferation but also increased cell sensitivity to reactive oxygen species, enhancing the apoptotic effect induced by CyI and achieving synergistic photo-chemotherapy. Moreover, BMC could induce macrophages to reprogram into anti-inflammatory M2 macrophages. This study provides innovative approaches for RA treatment via macrophage apoptosis and re-polarization.

The SERPINB4 gene mutation identified in twin patients with Crohn’s disease impaires the intestinal epithelial cell functions

Crohn’s disease (CD) is a chronic inflammatory autoimmune disease of unknown etiology. To identify new targets related to the initiation of CD, we screened a pair of twins with CD, which is a rare phenomenon in the Chinese population, for genetic susceptibility factors. Whole-exome sequencing (WES) of these patients revealed a mutation in their SERPINB4 gene. Therefore, we studied a wider clinical cohort of patients with CD or ulcerous colitis (UC), healthy individuals, and those with a family history of CD for this mutation by Sanger sequencing. The single-nucleotide difference in the SERPINB4 gene, which was unique to the twin patients with CD, led to the substitution of lysine by a glutamic acid residue. Functional analysis indicated that this mutation of SERPINB4 inhibited the proliferation, colony formation, wound healing, and migration of intestinal epithelial cells (IECs). Furthermore, mutation of SERPINB4 induced apoptosis and activated apoptosis-related proteins in IECs, and a caspase inhibitor significantly reduced these effects. Transcriptome sequencing revealed that the expression of genes encoding proinflammatory proteins (IL1B, IL6, IL17, IL24, CCL2, and CXCR2) and key proteins in the immune response (S100A9, MMP3, and MYC) was significantly upregulated during SERPINB4 mutant-induced apoptosis. Thus, the heterozygous SERPINB4 gene mutation causes the dysfunction of IECs, which would disrupt the intestinal epithelial barrier and contribute to the development of intestinal inflammation. The activation of SERPINB4 might represent a novel therapeutic target for inflammatory bowel disease.

Application of the Monoclonal Autoantibody and Its Target Protein Derived from the Peripheral Blood of SLE Patients in Serological Diagnosis and Differential Diagnosis of SLE

ABSTRACT Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with limited reliable diagnostic biomarkers. This study evaluates the utility of DEAD-box helicase 5 (DDX5) as a diagnostic and differential marker for SLE and assesses the performance of a capture bead-based flow cytometry (CBFCM) method for detecting serum proteins. Method Serum samples were collected from 52 patients with SLE, 38 patients with rheumatoid arthritis (RA), 49 patients with lung cancer (LC), and 50 healthy controls (HCs). Levels of DDX5, anti-DDX5, anti-dsDNA, and anti-Sm were quantified using enzyme-linked immunosorbent assay (ELISA) and CBFCM. Results Serum DDX5 levels were significantly elevated in patients with SLE compared to patients with RA and HCs, correlating with the SLE activity. DDX5 demonstrated strong discriminatory power between SLE and RA. Combining DDX5, anti-dsDNA, and anti-Sm as biomarkers yielded an area under the curve (AUC) of 0.976 for SLE diagnosis. Decision curve analysis indicated a high clinical benefit from the combined biomarkers. The sensitivity and specificity of DDX5 were 66.11% and 88.89% for ELISA, and 72% and 91.3% for CBFCM. Discussion DDX5 shows promise as a novel serological biomarker for SLE diagnosis and differential diagnosis. Additionally, CBFCM outperforms ELISA in detecting soluble serum proteins.

Clinical patterns of vitiligo in Japan: A descriptive study using the JMDC claims database.

Vitiligo is a chronic autoimmune disorder that profoundly impacts patients' quality of life. Real-world data on vitiligo in Japan are limited. This descriptive, cross-sectional study used a claims database to evaluate vitiligo prevalence, patient demographics, treatments, and comorbidities in Japanese patients with vitiligo. Patients with claims for a vitiligo diagnosis in the JMDC database from January 2010 to December 2022 were included. Annual vitiligo prevalence, comorbidities, treatments, and medical facility visits were analyzed. Of 16 947 087 patients in the database during the 13-year analysis period, a total of 26 358 patients (0.16%, 95% confidence interval 0.15-0.16) had a diagnosis of vitiligo. The standardized prevalence of vitiligo by sex and age in Japan remained generally consistent between 2010 (0.051%) and 2022 (0.056%). Atopic dermatitis was the most prevalent comorbidity. Comorbid atopic dermatitis prevalence increased between 2010 (21.8%) and 2022 (34.0%), and was highest among children aged 5-9 years. Other common comorbidities in 2022 included hypertension (10.4%), dyslipidemia (8.0%), anxiety disorder (7.4%), and psoriasis (7.0%). Topical corticosteroids were the most commonly used treatment throughout the period analyzed. Between 2010 and 2022, topical corticosteroid use decreased from 75.1% to 66.9%, and the use of narrowband ultraviolet B procedures increased from 19.2% to 28.1%. Mean duration of care was 12.9 months (standard deviation 20.5 months) and the median total number of outpatient medical facility visits was 3.0 (interquartile range 1.0-12.0). Key limitations include age and occupational biases in the JMDC database and potential misclassification of comorbidities due to off-label treatment coding. Despite limitations in using a claims database, this study demonstrates consistent vitiligo prevalence in Japan, a high comorbidity burden, and evolving treatment patterns. Findings may guide clinical practice and treatment guidelines to improve management of vitiligo in Japanese patients.

Dietary Interventions, Supplements, and Plant-Derived Compounds for Adjunct Vitiligo Management: A Review of the Literature.

Vitiligo is a chronic autoimmune pigmentation disorder shaped by a complex interplay of genetic predispositions and environmental triggers. While conventional therapies-phototherapy, corticosteroids, and immunosuppressants-can be effective, their benefits are often partial and temporary, with recurrence common once treatment stops. As such, there is increasing interest in exploring complementary approaches that may offer a more sustainable impact. Emerging evidence suggests that macronutrient and micronutrient-level changes could be beneficial for managing progression and, in some cases, facilitating repigmentation. Antioxidant-rich foods, such as apples, green tea, Indian gooseberry, onions, and peppers, may help mitigate oxidative stress, while inflammatory foods, such as gluten and high-phenol nuts and berries, may exacerbate the condition. Certain supplements, including high-dose vitamin D, vitamin C, vitamin E, and selenium, may enhance phototherapy outcomes. Omega-3 and other unsaturated fatty acids, in addition to prebiotics and probiotics, are under active investigation for their roles in gut health and immune regulation. Notably, plant-derived compounds, i.e., Ginkgo biloba, have demonstrated promise in promoting repigmentation and managing disease progression. However, it must be emphasized that these nutritional interventions remain exploratory, and more research is needed to establish their efficacy, safety, and optimal usage before they can be recommended as part of a standard treatment regimen.

Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatment.

Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood. We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays. We determined cytomegalovirus (CMV) serostatus and collected retrospective clinical information. We performed unsupervised and multivariable analyses. Unsupervised analyses revealed that MS immune profile was characterized by low relative levels of anti-inflammatory/neuroprotective factors IL-4, IL-10, TNF, and β-NGF but high levels of growth factors EGF and bFGF. Serum levels of IL-4, β-NGF, IL-27, BDNF, and leptin were significantly influenced by sex and/or CMV status. IL-4 and β-NGF levels were lower in untreated PwMS compared to controls, while EGF and bFGF levels were influenced by age and markedly elevated in PwMS in multivariable analysis. Samples from treated PwMS, but not untreated PwMS, showed lower levels of BDNF and TNF than controls. Initiation of high efficacy DMTs, but not low efficacy DMTs, was associated with reduced levels of bFGF and EGF. Samples associated with distinct DMTs exhibited specific profiles for age-sensitive immune markers. Finally, lower levels of IL-6, TNF, IL-10, and β-NGF were observed at baseline in PwMS who subsequently experienced clinical failure after DMTs initiation. Age, sex, CMV status, and specific DMTs significantly influence levels of age-sensitive immune biomarkers associated with MS and must be considered when investigating inflammation-related biomarkers. This work was supported by a Grant for Multiple Sclerosis Innovation by Merck KGaA (ID: 10.12039/100009945).

Oligodendrocyte Injury in Multiple Sclerosis.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS), marked by inflammation, demyelination, and significant oligodendrocyte injury. This disease arises from a complex interplay of genetic predispositions and environmental triggers that drive immune-mediated damage to oligodendrocytes and myelin proteins. This research paper explores the multifaceted aspects of oligodendrocyte injury in MS, ranging from underlying pathophysiological mechanisms to potential therapeutic interventions and translational implications for clinical practice. Oligodendrocyte damage in MS occurs via multiple mechanisms, including metabolic stress, oxidative damage, and cytokine-induced apoptosis, mainly mediated by interferon-gamma (IFN-γ) signaling. This process exacerbates neuroinflammation and contributes to disease progression. Emerging therapeutic strategies, such as targeting metabolic pathways, reducing oxidative stress, and enhancing autophagy, have demonstrated potential in preclinical studies. Furthermore, stem cell therapies are being explored for their ability to regenerate oligodendrocytes and restore myelin integrity. Conclusions: The intricate interplay among oligodendrocyte injury, demyelination, and neuroinflammation is central to multiple sclerosis (MS) pathogenesis. Oligodendrocytes safeguard myelin in the CNS, facing challenges from immune attacks to metabolic stress. Understanding oligodendrocyte dysfunction is vital for targeted therapies that suppress immune damage and promote remyelination and CNS repair. MS's etiology,

Targeting p38 MAPK signaling pathway and neutrophil extracellular traps: An important anti-inflammatory mechanism of Huangqin Qingre Chubi Capsule in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common chronic autoimmune disease. Neutrophils release and their extracellular traps (NETs) tend to result in synovial inflammation and cartilage damage. Huangqin Qingre Chubi Capsule (HQC) is an important herbal formulation for RA treatment and has been used for many years. This study applied an interdisciplinary and integrated strategy combining clinical data, integrative bioinformatics, molecular modeling, and both in vitro and in vivo experiments to elucidate the efficacy and potential anti-inflammatory mechanisms of HQC for RA. Retrospective clinical data mining demonstrated that patients with RA treated with HQC exhibited recovery of immuno-inflammatory markers and self-perception. By applying network pharmacological analysis, molecular docking, molecular dynamics simulation, and cellular thermal shift assays, we determined that HQC can directly bind to MAPK14 and target p38 MAPK signaling pathway and NETs formation. Treatment of an adjuvant-induced arthritis rat model combining damp-heat patterns using HQC demonstrated it's effectiveness in reducing the severity of inflammatory arthritis in a dose-dependent manner and downregulated phosphorylation of p38 MAPK and NETs release. In vitro co-culture system mimicking inflammatory microenvironment of RA in vivo revealed that crosstalk between neutrophils (PMNs) and fibroblast-like synoviocytes (FLSs) was manifested by activation of p38 MAPK signaling pathway, release of NETs, and amplification of inflammation, which was blocked by HQC. Mechanistic validation using the p38 MAPK agonist diprovocim demonstrated that HQC inhibited NET formation by modulating the p38 MAPK pathway (mainly by inhibiting its phosphorylation) to exert anti-inflammatory effects. In conclusion, our interdisciplinary and integrated study demonstrated that HQC can target the p38 MAPK signaling pathway to inhibit NET formation and inflammatory response, thereby blocking the crosstalk between PMNs and FLSs to ameliorating RA.

Cerebrovascular risk in rheumatoid arthritis patients: insights from carotid artery atherosclerosis in the Paracelsus 10,000 study

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by systemic inflammation. While RA primarily affects the joints, its systemic effects may lead to an increased cerebro- and cardiovascular risk. Atherosclerosis of the carotid arteries is a significant risk factor for cerebrovascular events and serves as a surrogate marker for cardiovascular risk. This study explores the link between RA and carotid artery atherosclerosis with data from the Paracelsus 10,000 Study. Baseline assessments were conducted on individuals randomly selected from Salzburg and its surrounding regions. Participants diagnosed with RA based on ACR-EULAR classification criteria and who underwent carotid artery ultrasound were included. Data were gathered from a total of 9729 participants, among whom 299 were diagnosed with RA. Carotid arteries were examined using ultrasound imaging. The primary endpoint was the difference in the prevalence of plaque presence between the RA and non-RA groups. One univariate (Model I) and three multivariate analyses were conducted, with adjustments in Model II incorporating SCORE 2, while Model III accounted for metabolic syndrome, age and sex. Additionally, Model IV included further adjustments for high-sensitivity C-reactive protein (hs-CRP). Plaque presence was defined as the ultrasound detection of plaque formation larger than 0 mm2, regardless of whether it was unilateral or bilateral. Additional assessments included carotid stenosis, intima-media thickness (IMT) and total plaque area (TPA). RA patients had a higher prevalence of plaque (50%) compared to non-RA individuals (38%). The odds ratio (OR) for plaque presence in RA patients versus non-RA individuals was 1.64 (95% CI 1.30–2.06). This association persisted after adjusting for SCORE2, with an adjusted odds ratio (aOR) of 1.65 (95% CI 1.26–2.15). The association remained significant when adjusting for metabolic syndrome, age and sex (aOR = 1.32, 95% CI 1.02–1.72) and also in Model IV, which included further adjustment for hs-CRP (OR = 1.33, 95% CI 1.02–1.74). The findings underscore an increased risk of cerebrovascular disease associated with RA. This study highlights the importance of thorough cerebrovascular and cardiovascular risk assessments, along with proactive management, for RA patients to reduce this risk. Recognizing the substantial impact of RA on stroke and cerebrovascular disease is important for enhancing patient care strategies. Carotid ultrasound appears to be an effective method for atherosclerosis screening in RA patients.

Advanced oxidation protein products induce apoptosis in thyroid follicular epithelial cells through oxidative stress in Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is a chronic autoimmune disorder primarily driven by T cell. The apoptosis of the follicular thyroid cells plays an important role in HT apart from the lymphocyte-mediated cytotoxicity. Advanced oxidation protein products (AOPPs), resulting from oxidative stress, are known to be involved in various inflammatory diseases. However, their role in HT development has not been explored. Here, we discovered that AOPP levels were significantly elevated in thyroid tissues of both HT patients (Ctrl 4.12±0.56, HT 30.00±2.78; p<0.0001) and experimental autoimmune thyroiditis (EAT) mice (Ctrl 8.37±1.43, HT 55.82±2.87; p<0.0001), accompanied by extensive thyroid follicular epithelial cell apoptosis in HT patients (Ctrl 32.16±1.79, HT 147.10±13.32; p<0.0001) and EAT mice (Ctrl 66.78±6.72, HT 249.10±9.77; p<0.0001). In vitro study showed that AOPPs induced reactive oxygen species (ROS) production via nicotinamide adenine dinucleotide phosphate oxidase (NOX), leading to apoptosis in human thyroid follicular epithelial cell (Nthy-ori 3-1). Treatment with apocynin, a NOX inhibitor, reduced AOPP-induced ROS production and apoptosis in Nthy-ori 3-1 cells, and in turn alleviated thyroid follicular epithelial cell apoptosis and autoimmune thyroiditis symptoms in mice. Mechanistically, AOPP treatment activated JNK pathway, leading to the downregulation of Bcl-2, upregulation of Bax, the mitochondrial membrane potential depolarization and consequently triggered the activation of mitochondria-dependent intrinsic apoptosis pathway. Collectively, our findings highlight the promotive roles of AOPP in HT and provide an attractive therapeutic target for HT therapy.

EXamining the feasibility of exerCisE to manage symptoms of Lupus (EXCEL): a protocol for a randomised controlled pilot study

IntroductionSLE is a chronic autoimmune disease that results in sustained hyperactivation of innate and adaptive immune cells and widespread inflammatory damage. Regular exercise reduces SLE symptoms including fatigue and joint...

Multiple sclerosis: peculiarities of providing high-quality medical care to patients in the realities of Ukraine

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system, which is one of the most common causes of progressive disability among young people. This disease significantly affects the quality of life of patients and their families and is also accompanied by significant economic costs. Early diagnosis and early initiation of treatment of patients with MS help prevent the development of exacerbations, disability, premature death and improve quality of life. Today, awareness of MS has increased, more effective methods of diagnosis and therapy of patients with MS have become available. This has led to a reduction in the diagnostic delay between the detection of symptoms and making a reliable diagnosis, as well as to the postponement of severe disability. Multidisciplinary co-operation of specialists at all levels of medical care and close co-operation between the doctor and the patient is essential for optimal clinical management. The article systematizes current know-ledge on the main approaches to the diagnosis and treatment of patients with MS in Ukraine.

Effectiveness of Ocrelizumab on Disease Progression and Disability Status in Multiple Sclerosis Patients: A Two-Year Prospective Cohort Study.

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation and neurodegeneration. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has shown promise in reducing disease activity in MS patients. This prospective study aims to assess the effectiveness of ocrelizumab in reducing confirmed disability progression in patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) over a two-year period. By evaluating clinical data, and MRI findings, this study seeks to provide comprehensive insights into ocrelizumab's impact on disease dynamics and disability. Materials and Methods: Ninety-eight patients aged 18 to 65 with confirmed MS were enrolled under ocrelizumab therapy at the Neurology Department of "Pius Brinzeu" Clinical Emergency Hospital in Romania between July 2020 and July 2024. Participants were assessed at baseline and every six months over two years. The key outcomes measured were changes in the Expanded Disability Status Scale (EDSS) as a measure of confirmed disability progression (CDP), annualized relapse rate (ARR), and MRI findings. Results: Over the two-year period, the mean EDSS score significantly decreased from 5.2 ± 1.8 to 4.6 ± 1.7 (mean change = -0.6 ± 0.9; p = 0.032), indicating improved neurological function. The proportion of patients experiencing relapses dropped markedly from 61.2% to 14.3% (p < 0.001). The MRI results showed significant reductions in patients with new or enlarging T2 lesions from 68.4% to 27.6% (p < 0.001) and gadolinium-enhancing lesions from 44.9% to 15.3% (p < 0.001). Patients previously treated with natalizumab exhibited a greater reduction in EDSS scores (-1.0 ± 0.8; p = 0.001) compared to other treatments. Multivariate regression identified the baseline EDSS score (β = 0.65; p < 0.001), previous natalizumab use (β = -0.30; p = 0.013), and age at diagnosis (β = 0.02; p = 0.048) as significant predictors of two-year EDSS scores. While markers of active inflammation decreased, the proportion of patients with brain atrophy increased from 31.6% to 43.9% (not statistically significant; p = 0.105). SPMS patients had higher rates of brain atrophy at baseline (61.1% vs. 25.0%; p = 0.007) and at two years (100.0% vs. 31.3%; p < 0.001) compared to RRMS patients. Conclusions: Ocrelizumab effectively reduced disease activity and improved neurological disability over two years in both RRMS and SPMS patients. Significant reductions in relapse rates and MRI markers of inflammation were observed. Previous natalizumab treatment was associated with greater improvements. Despite these benefits, the progression of neurodegeneration, particularly brain atrophy in SPMS patients, underscores the need for additional strategies targeting neurodegenerative aspects of MS.

Systemic Inflammatory Immune Index (SII) Predicts Disease Activity in Systemic Lupus Erythematosus (SLE) Patients: A Cross-Sectional Study

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread inflammation and diverse clinical manifestations. The systemic inflammatory immune index (SII), calculated as platelet count * neutrophil count/lymphocyte count, has emerged as a potential marker of systemic inflammation in various conditions. This study aimed to investigate the relationship between SII and disease activity in SLE patients. Methods: We conducted a cross-sectional study involving 60 SLE patients diagnosed according to the 2019 EULAR/ACR classification criteria. Demographic and clinical data were collected, and disease activity was assessed using the Mexican Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI). Blood samples were analyzed to determine SII values. Statistical analysis included Spearman's correlation to assess the relationship between SII and MEX-SLEDAI scores. Results: The study population predominantly consisted of women (98.3%), with a median age of 29 years. A strong positive correlation was observed between SII and MEX-SLEDAI scores (r = 0.931, p &lt; 0.001). Patients with higher SII values exhibited significantly greater disease activity. Conclusion: Our findings suggest that SII is a promising predictor of disease activity in SLE patients. This readily available index may aid clinicians in assessing disease severity and tailoring treatment strategies. Further research is warranted to validate these findings and explore the utility of SII in monitoring disease progression and treatment response.

Influence of kinesiophobia on activity, function, and anxiety levels in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disorder that causes joint inflammation and affects quality of life. Appropriate physical activity can enhance joint function and lower cardiovascular disease risk. However, individuals with RA often have reduced physical activity levels, likely due to kinesiophobia, or fear of movement.AimThis study aimed to assess the prevalence of kinesiophobia among RA patients and its influence on functional impairment, physical activity, and pain-related anxiety.MethodsUsing a convenience sampling method, we surveyed 350 RA patients attending outpatient clinics in the rheumatology and immunology departments of three tertiary hospitals in Henan Province, China, from August 18 to September 1, 2023. Participants completed the Tampa Scale of Kinesiophobia (TSK), the Signals of Functional Impairment Scale (SOFI), the International Physical Activity Scale—Short Form (IPAQ-SF), and the Pain Anxiety Symptoms Scale-20 (PASS-20). The Disease Activity Score 28 (DAS28) was retrieved for each participant to assess disease activity in RA patients. Descriptive analysis, Chi-square tests, Spearman correlation, and multiple linear regression assessed factors influencing kinesiophobia, with significance set at p &amp;lt; 0.05.ResultsResults indicated that 70.86% of participants experienced kinesiophobia, which was positively correlated with functional impairment and pain-related anxiety, while inversely related to physical activity levels (p &amp;lt; 0.001). Regression analysis revealed that kinesiophobia was explained by 65.5% of the variance, with gender, education level, functional impairment, pain-related anxiety, and pain severity identified as significant predictors (p &amp;lt; 0.05).ConclusionThe findings suggest that RA patients exhibit a high prevalence of kinesiophobia, predominantly influenced by factors such as gender, lower educational attainment, increased pain levels, greater functional impairment, and pain-related anxiety. Notably, physical activity levels did not serve as a predictor of kinesiophobia in this cohort.

Changes and Long-Term Effects of the Immune System after COVID-19 Infection

Following the pandemic in 2020, physical health has generally declined. All of this is brought on by modifications to the body's immune system and the consequences of sequelae. The current research gap is caused by the neglect of COVID-19's after effects. In this paper, the relationship between immune system changes, complications and their physical conditions was studied, and preliminary results on the harm and prevention of the sequelae were obtained. The immune system's alterations during the epidemic infection and its consequences are the main topics of this article, including cytokine storms, inflammatory responses, and changes in immune cells. At the same time, the article explores the relationship between complications and underlying health conditions, such as chronic diseases and autoimmune diseases, and the harm they cause. Through observation and analysis in the later stages of the epidemic, the article explores the reasons for the general decline in people's physical fitness and changes in the immune system. In the future, it is hoped that there will be improvements in disease analysis and prevention measures after pandemic diseases.

Developing predictive models for tocilizumab response in rheumatoid arthritis: a gene expression and machine learning approaches

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease treated with tocilizumab in patients unresponsive to methotrexate. This study aimed to identify gene expression profiles and predictive models for tocilizumab treatment response in RA patients. Methods: Using the GSE78068 dataset from 38 RA patients, we identified differentially expressed genes between remission and non-remission groups. Predictive models were created using CART, random forest, and SVM techniques, with model genes selected through LASSO regression. Gene set enrichment and immune cell landscape analyses were performed to understand biological pathways and immune cell composition. Results: Analysis revealed 40 differentially expressed genes, with LASSO regression identifying 8 model genes significantly associated with remission. The SVM-based model achieved the highest performance (AUC=1.0, Brier score=0.025). Conclusions: This study developed an effective 8-gene model for predicting tocilizumab treatment response, potentially supporting personalized therapy in RA patients.

Analyzing How Zhizi Baipi Decoction Regulates VEGF to Suppress RA Angiogenesis Using Network Pharmacology and Experimental Validation.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily manifests with symptoms such as heat and toxin. However, the key components and molecular mechanisms of Zhizi Baipi decoction (ZBD) in the treatment of RA are still unclear. The study aimed to explore the mechanism of action of ZBD for treating RA through ingredient analysis, network pharmacology, and experimental validation. The chemical constituents of ZBD were identified by ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MSE). Additionally, the active ingredients of ZBD treating RA were screened by network pharmacology and using molecular docking to verify the binding energy of the active ingredients and ZBD's targets. Then we elucidated ZBD's mechanism of action on collagen-induced arthritis (CIA) model rats. Subsequently, experimental validations were used to validate the findings of network pharmacology. A total of 84 chemical constituents was identified by UPLC-Q-TOF-MSE. The results of network pharmacology indicated that ZBD could exert its therapeutic effect on RA through the vascular endothelial growth factor (VEGF) pathway. Molecular docking revealed a strong binding capacity between the target KDR and the active ingredients. Additionally, we quantified the five active ingredients of ZBD. Invivo experiments demonstrated that ZBD inhibited synovial angiogenesis and alleviated the occurrence and progression of RA. Overall, ZBD has a significant therapeutic effect on RA. The results of qualitative analysis, network pharmacology, molecular docking, and invivo experiments indicated that the main active components of ZBD could modulate the VEGF pathway to treat RA.

Associations of aged neutrophils with disease activity in primary Sjögren's syndrome

AbstractBackgroundPrimary Sjögren's syndrome (pSS) is a chronic autoimmune disease that primarily affects exocrine glands. This study aimed to investigate the correlation between aged neutrophils and disease activity in patients with pSS.MethodsThis study included 21 patients diagnosed with pSS and 32 healthy controls (HCs) at Shanghai East Hospital between September 2021 and May 2023. Peripheral blood samples were collected from them. Neutrophil subsets were identified using cell surface markers (CD62L, CXCR4, CD11b, and CXCR1) and analyzed using flow cytometry. Clinical data, including the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) and serum ferritin levels, were also collected at admission.ResultsSerum ferritin levels were associated with the ESSDAI and neutrophil‐to‐lymphocyte ratio in patients with pSS. Our study revealed a significant increase in the frequency of aged neutrophils in patients with pSS compared to HCs (p &lt; 0.05). The frequency of aged neutrophils significantly correlated with ESSDAI and ferritin levels in patients with pSS (p &lt; 0.05). We generated a receiver operating characteristic (ROC) curve to evaluate the diagnostic utility of aged neutrophils in pSS. ROC analysis showed an area under the curve of 0.8036, with a p‐value of 0.0002.ConclusionsThis study confirmed that patients with pSS exhibit a higher percentage of aged neutrophils. Furthermore, aged neutrophils may serve as diagnostic markers of pSS.