ABSTRACT
Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors of HZ development in patients receiving JAKi therapy would be clinically helpful. We investigated HZ's incidence rates (IR), identified the risk factors, and further assessed their influence on HZ development in RA patients undergoing JAKi therapy. We retrospectively evaluated 249 RA patients who received JAKi therapy between 2015 and 2023. Data regarding clinical characteristics, HZ reactivation, HZ vaccination status, and concomitant medication use were collected. Among 249 JAKi-treated patients, 44 developed new-onset HZ (tofacitinib, 28/142; baricitinib, 6/35; upadacitinib,10/72), with an IR of 5.11/100patient-years. Multivariate analysis revealed significant predictors of HZ development: a long JAKi exposure period, prior HZ or COVID-19 history, and concomitant high-dose corticosteroids use. The interval between JAKi initiation and HZ development was significantly shorter in patients with prior HZ history than in those without (median, 6.5 months versus 33.5 months, p < 0.001), suggesting "biphasic" emergence of HZ. Only one patient who had experienced an HZ episode while receiving JAKi developed recurrent HZ. None of the seventeen patients immunized with the non-live recombinant zoster vaccine developed HZ. Our JAKi-treated patients had elevated HZ risks, a class effect across different JAKi. A long exposure period, prior history of HZ or COVID-19, and concomitant high-dose corticosteroid treatment may further increase the risk. The emergence of HZ shows a biphasic pattern: early HZ development in patients with prior HZ and late development in those without. Key Points ⢠An increased risk of HZ was observed in Taiwanese RA patients treated with JAKi, presenting as a class effect. ⢠Patients with a long JAKi exposure period, prior history of HZ or COVID-19, and concomitant use of high-dose corticosteroids were at high risk of HZ while receiving JAKi therapy. ⢠The interval between JAKi initiation and HZ occurrence was shorter in patients with prior HZ than in those without, showing "biphasic" emergence.
Subject(s)
Adrenal Cortex Hormones , Arthritis, Rheumatoid , Azetidines , Herpes Zoster , Janus Kinase Inhibitors , Humans , Arthritis, Rheumatoid/drug therapy , Herpes Zoster/chemically induced , Herpes Zoster/prevention & control , Herpes Zoster/epidemiology , Retrospective Studies , Male , Female , Middle Aged , Aged , Janus Kinase Inhibitors/adverse effects , Janus Kinase Inhibitors/therapeutic use , Risk Factors , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Azetidines/adverse effects , Azetidines/therapeutic use , Sulfonamides/adverse effects , Sulfonamides/administration & dosage , Sulfonamides/therapeutic use , Piperidines/adverse effects , Piperidines/therapeutic use , Piperidines/administration & dosage , Incidence , Pyrazoles/adverse effects , Purines/adverse effects , Pyrimidines/adverse effects , Heterocyclic Compounds, 3-Ring/adverse effects , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/administration & dosage , COVID-19/epidemiology , Adult , SARS-CoV-2 , Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic useABSTRACT
Introduction: In medical education, the clerkship phase is a demanding period during which medical students learn to navigate the responsibilities of medical school and clinical medicine. Grit, a personal quality regarded as a non-cognitive trait, refers to perseverance and passion; specifically, it represents the ability to endure hardship and work industriously toward a goal. Most studies analysed grit as a single concept and few studies have investigated the effect of grit on the well-being of medical students through the whole-specialty training (i.e. surgical and non-surgical specialty rotations) required in clinical clerkships. Therefore, this study investigated whether associations exist between medical students' grit, measured by the two subconstructs of perseverance and passion, and their well-being during clerkships in surgical and non-surgical specialty units. Methods: This one-year prospective web-based questionnaire study enrolled fifth-year medical students at a tertiary medical centre in central Taiwan between September 2017 and July 2018 in their first-year clerkship. The students' sex, age, and grit were measured at the start of their clerkship. Routine surveys were conducted over one year to assess burnout and compassion satisfaction for students' well-being, and the training specialty characteristics of the surgical and non-surgical specialty departments were recorded. This study included 92 medical students and 1,055 survey responses from individual specialty rotations. Descriptive, univariate and multivariate analyses were performed. Results: Our results revealed that medical students' perseverance, as part of grit, was related to lower burnout and higher compassion satisfaction during clerkships, but not the subconstruct of passion. Moreover, the positive trait of perseverance measured in our study had greater explanatory power for compassion satisfaction than for burnout. Furthermore, the results revealed that older medical students suffered from less burnout than their younger counterparts, and that male medical students expressed higher compassion satisfaction than their female counterparts. Discussion: Perseverance, as a subconstruct of grit, is a positive personal quality for medical students' clerkships, and methods driving the cultivation of perseverance in medical education should be considered. In addition, even though positive traits such as perseverance equipped medical students for compassion satisfaction, additional factors attributed to medical students' burnout must be identified.
ABSTRACT
Anti-interferon (IFN)-γ autoantibodies are linked to varicella zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. Serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ-inducible protein-10 (IP-10) were measured by ELISA. Among the 66 enrolled RA patients, 24 developed new-onset HZ. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21 pg/mL, interquartile range (IQR) 77.63-150.30 pg/mL versus 142.3 pg/mL, IQR 106.7-175.6 pg/mL, p < 0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8 ng/mL, IQR 21.0-38.2 ng/mL versus 10.5 ng/mL, IQR 9.9-15.0 ng/mL, p < 0.005). Our results suggest an association between reduced MCP-1 levels and HZ development in JAKi-treated RA patients. High-titer anti-IFN-γ autoantibodies may be related to severe HZ in these patients.
Subject(s)
Fibromyalgia , Irritable Bowel Syndrome , Restless Legs Syndrome , Humans , Restless Legs Syndrome/diagnosis , Restless Legs Syndrome/epidemiology , Fibromyalgia/diagnosis , Fibromyalgia/epidemiology , Irritable Bowel Syndrome/diagnosis , Irritable Bowel Syndrome/epidemiology , Irritable Bowel Syndrome/complications , Female , China/epidemiology , Middle Aged , Temporomandibular Joint Disorders/diagnosis , Temporomandibular Joint Disorders/epidemiology , Adult , Male , East Asian PeopleABSTRACT
OBJECTIVE: This study aimed to assess the incidence and risk factors surrounding mental illnesses in patients diagnosed with systemic autoimmune rheumatic diseases (SARDs). METHODS: This retrospective cohort study used nationwide, population-based claim data taken from Taiwan's National Health Insurance Research Database (NHIRD) to identify patients certified as having a catastrophic illness for Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), Systemic sclerosis (SSc), Dermatomyositis (DM), Polymyositis (PM) or Sjogren's syndrome (SS) from the years 2002-2020. We furthermore calculated the incidence of mental illness in patients diagnosed with SARDs while exploring factors associated with the development of mental illness using multivariable Cox regression analysis shown as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among the 28 588 participants, the average age was 47.4 (SD 14.9) years, with most participants being female (76.4%). When compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.20, 95% CI: 1.10-1.32), SS (HR: 1.29, 95% CI: 1.19-1.39), and DM (HR: 1.28, 95% CI: 1.04-1.32) showed a significantly increased risk of developing mental illness. Additionally, when compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.32, 95% CI: 1.21-1.44), SSc (HR: 1.20, 95% CI: 1.02-1.41), SS (HR: 1.17, 95% CI: 1.08-1.26), DM (HR: 1.73, 95% CI: 1.44-2.07), and PM (HR: 1.64, 95% CI: 1.32-2.03) showed a significantly increased risk of antidepressant use. CONCLUSIONS: This population-based cohort study revealed that patients diagnosed with SLE, SS and DM had significantly higher risks of developing mental illness when compared with patients with RA.
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Objectives: Numerous cases of long coronavirus disease (long COVID) have been reported in patients with autoimmune rheumatic diseases (ARDs). Despite the reviews on clinical manifestations of long COVID in the general population, systematic reviews on ARD patients are scarce. Herein, we conducted a systematic review and meta-analysis on the prevalence and characteristics of long COVID in ARD patients. Methods: We searched the literature in PubMed and Embase as of 27 December 2022. Cohort, cross-sectional and case-control studies relevant to long COVID in ARD patients were collected. Stratification based on the severity of COVID infection and subtypes of rheumatic diseases [systemic autoimmune rheumatic disease (SARD) vs non-autoimmune rheumatic disease (NARD)] was also undertaken. A random-effects model was used in the meta-analysis. Results: A total of 15 relevant studies were identified from the literature. The prevalence of long COVID was 56% (95% CI 34, 76) in 2995 patients. Hospitalized COVID patients had a higher proportion of long COVID than non-hospitalized patients. The prevalence of long COVID was similar between SARD and NARD patients. In terms of symptoms, fatigue, arthralgia and pain were commonly reported in long COVID patients with ARDs. Conclusion: The characteristics of long COVID in ARD patients are generally similar to those in the general population despite a higher prevalence and a higher proportion of arthralgia and pain.
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BACKGROUND: Our cost-of-illness (COI) model adopted both payer and societal perspectives over a time horizon of 5 years to measure the economic burden of systemic lupus erythematosus (SLE) in Taiwan. METHODOLOGY: A prevalence-based model was established to estimate the economic consequences of SLE after diagnosis in Taiwan. The model included four health states: (i) the three phenotypes representing mild, moderate, and severe SLE, and (ii) death. The inputs were obtained from a literature review of all the clinical trials and validated using a Delphi panel. The Delphi panel's insights included commonly used treatment strategies for patients with SLE within the Taiwanese healthcare system. The costs mentioned in this model are disease management, monitoring, transient event, and indirect costs. One-way sensitivity analyses were conducted to assess the model uncertainty. RESULTS: The number of patients with SLE in our COI model was 20,189. At diagnosis, the number of SLE patients with mild, moderate, and severe phenotypes was 5,916, 12,255, and 2019, respectively. The total SLE cost in Taiwan over 5 years from both payer and societal perspectives was estimated at TWD 3.9 and 47 billion, respectively. The costs per patient per year from the payer and societal perspective were TWD 38,775 ($2,758) and TWD 466,119 ($33,152), respectively. CONCLUSION: The findings demonstrated that the burden of SLE in Taiwan over a time horizon of 5 years is substantially high, mainly due to the consequences of economic loss as it affects women and men during their working age, in addition to the costs of SLE management and its consequences, such as flares, infection, and organ damage. Therefore, more attention should be paid to limiting the progression of SLE and the occurrence of flares, and further economic evaluations are necessary to assess novel treatment strategies that could control the disease.
Subject(s)
Financial Stress , Lupus Erythematosus, Systemic , Female , Humans , Male , Cost of Illness , Lupus Erythematosus, Systemic/drug therapy , Retrospective Studies , Taiwan/epidemiologyABSTRACT
Background: Non-alcoholic fatty liver disease (NAFLD) is prevalent among rheumatoid arthritis (RA) patients, but its pathogenesis has rarely been explored. Galectin-9 (Gal-9) interacts with T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3) expressed on hepatocytes and thus regulates T cell proliferation in a murine model of NAFLD. We aimed to examine the pathogenic role of the Gal-9/TIM-3 pathway in RA-NAFLD. Methods: Serum levels of Gal-9, soluble TIM-3 (sTIM-3), fatty acid-binding proteins (FABP)1, and FABP4 were determined by ELISA in forty-five RA patients and eleven healthy participants. Using Oil-red O staining and immunoblotting, we examined the effects of Gal-9 and free fatty acid (FFA) on lipid accumulation in human hepatocytes and FABP1 expression. Results: Serum Gal-9, sTIM-3 and FABP1 level were significantly higher in RA patients (median 5.02 ng/mL, 3.42 ng/mL, and 5.76 ng/mL, respectively) than in healthy participants (1.86 ng/mL, 0.99 ng/mL, and 0.129 ng/mL, all p < 0.001). They were also significantly higher in patients with moderate-to-severe NAFLD compared with none-to-mild NAFLD (p < 0.01; p < 0.05; and p < 0.01, respectively). Serum Gal-9 levels were positively correlated with sTIM-3, FABP1, FABP4 levels, and ultrasound-fatty liver score, respectively, in RA patients. Multivariate regression analysis revealed that Gal-9 (cut-off>3.30) was a significant predictor of NAFLD development, and Gal-9 and sTIM-3 were predictors of NAFLD severity (both p < 0.05). The cell-based assay showed that Gal-9 and FFA could upregulate FABP1 expression and enhance lipid droplet accumulation in hepatocytes. Conclusion: Elevated levels of Gal-9 and sTIM3 in RA patients with NAFLD and their positive correlation with NAFLD severity suggest the pathogenic role of Gal-9 signaling in RA-related NAFLD.
ABSTRACT
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by chronic synovitis and the progressive destruction of cartilage and bone. RA is commonly accompanied by extra-articular comorbidities. The pathogenesis of RA and its comorbidities is complex and not completely elucidated. The assembly of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activates caspase-1, which induces the maturation of interleukin (IL)-1ß and IL-18 and leads to the cleavage of gasdermin D with promoting pyroptosis. Accumulative evidence indicates the pathogenic role of NLRP3 inflammasome signaling in RA and its comorbidities, including atherosclerotic cardiovascular disease, osteoporosis, and interstitial lung diseases. Although the available therapeutic agents are effective for RA treatment, their high cost and increased infection rate are causes for concern. Recent evidence revealed the components of the NLRP3 inflammasome as potential therapeutic targets in RA and its comorbidities. In this review, we searched the MEDLINE database using the PubMed interface and reviewed English-language literature on the NLRP3 inflammasome in RA and its comorbidities from 2000 to 2023. The current evidence reveals that the NLRP3 inflammasome contributes to the pathogenesis of RA and its comorbidities. Consequently, the components of the NLRP3 inflammasome signaling pathway represent promising therapeutic targets, and ongoing research might lead to the development of new, effective treatments for RA and its comorbidities.
Subject(s)
Arthritis, Rheumatoid , Autoimmune Diseases , Humans , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Arthritis, Rheumatoid/drug therapy , Comorbidity , Interleukin-1betaABSTRACT
BACKGROUND: Although the non-alcoholic fatty liver disease (NAFLD) is prevalent in the general population, NAFLD risk in newly diagnosed rheumatoid arthritis (RA) has rarely been explored. In this population-based cohort, we examined NAFLD risk in patients with RA and identified the potential risk factors. DESIGN: Retrospective study. SETTING: Taiwan. PARTICIPANTS: 2281 newly diagnosed patients with RA and selected 91 240 individuals without RA to match with patients with RA (1:40) by age, gender, income status and urbanisation level of the residence. OUTCOMES: In this retrospective study using the 2000-2018 claim data from two-million representative Taiwanese population, we identified and compared the incidence rates (IRs) of NAFLD and alcoholic fatty liver disease (AFLD) between RA and non-RA groups. Using multivariable regression analyses, we estimated adjusted HR (aHR) of NAFLD development in patients with RA compared with individuals without RA, with 95% CIs. RESULTS: The incidences of NALFD and AFLD were not significantly different between individuals with RA and without RA during the 17-year follow-up period. However, patients with RA had significantly increased NAFLD risk during the first 4 years after RA diagnosis, with IR ratio of 1.66 fold (95% CI 1.18 to 2.33, p<0.005), but the risk was reduced after the first 4 years. Multivariable regression analyses revealed that aHR was 2.77-fold greater in patients not receiving disease-modifying anti-rheumatic drugs therapy than in non-RA subjects (p<0.05). Old age, women, low-income status and obesity could significantly predict NAFLD development. CONCLUSIONS: We demonstrated elevated risk of NAFLD in patients with RA during the first 4 years after RA diagnosis, and old age, women, low-income status and obesity were significant predictors of NAFLD.
Subject(s)
Arthritis, Rheumatoid , Non-alcoholic Fatty Liver Disease , Humans , Female , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Retrospective Studies , Cohort Studies , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Risk Factors , ObesityABSTRACT
OBJECTIVES: To assess the association between antirheumatic drugs and of the risk of nonalcoholic fatty liver disease (NAFLD) in a nationwide rheumatoid arthritis (RA) cohort. METHODS: Using claim data from the 2000-2020 National Health Insurance Research Database, we identified 21 457 incident patients with RA from 2002 to 2020 without prior liver diseases. A time-varying multivariable Cox regression model was applied to estimate for the association of NAFLD with the use of antirheumatic drugs after adjusting potential confounders, show as adjusted hazard ratios (aHRs) with 95% confidence interval (CIs). Subgroup analyses were conducted based on age-, sex-, and obesity-related comorbidities. RESULTS: Multivariable time-dependent Cox regression analyses showed that defined daily dose (DDD) of NSAID (aHR, 1.03; 95% CI: 1.02-1.05) and prednisolone equivalent dose >5 mg/day (aHR, 2.39; 95% CI: 1.85-3.09) were risk factors of NAFLD in patients with RA, while prednisolone equivalent dose ≤5 mg/day (aHR of 0.53; 95% CI: 0.40-0.71) and HCQ use (aHR of 0.75; 95% CI: 0.60-0.93) were associated with a decreased risk of NAFLD. In addition, a history of hospitalizations, number of outpatient visits, age, male, and leflunomide use were associated with the development of NAFLD in some subgroups. CONCLUSION: This study reveals that NSAID use and prednisolone equivalent dose >5 mg/day were associated with an increased risk of NAFLD in patients with RA, while the use of HCQ and prednisolone equivalent dose ≤5 mg/day decreased the risk of NAFLD.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Non-alcoholic Fatty Liver Disease , Humans , Male , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/chemically induced , Antirheumatic Agents/adverse effects , Cohort Studies , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Risk Factors , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Prednisolone/therapeutic useABSTRACT
Human parvovirus B19 (B19V) is a single-stranded non-enveloped DNA virus of the family Parvoviridae that has been associated with various autoimmune disorders. Systemic sclerosis (SSc) is an autoimmune connective tissue disorder with high mortality and has been linked to B19V infection. However, the precise mechanism underlying the B19V contribution to the development of SSc remains uncertain. This study investigated the impacts of the functional B19V-VP1 unique region (VP1u) in macrophages and bleomycin (BLE)-induced SSc mice. Cell experimental data showed that significantly decreased viability and migration of both B19V-VP1u-treated U937 and THP-1 macrophages are detected in the presence of celastrol. Significantly increased MMP9 activity and elevated NF-kB, MMP9, IL-6, TNF-α, and IL-1ß expressions were detected in both B19V-VP1u-treated U937 and THP-1 macrophages. Conversely, celastrol revealed an inhibitory effect on these molecules. Notably, celastrol intervened in this pathogenic process by suppressing the sPLA2 activity of B19V-VP1u and subsequently reducing the inflammatory response. Notably, the administration of B19V-VP1u exacerbated BLE-induced skin fibrosis in mice, with augmented expressions of TGF-ß, IL-6, IL-17A, IL-18, and TNF-α, ultimately leading to α-SMA and collagen I deposits in the dermal regions of BLE-induced SSc mice. Altogether, this study sheds light on parvovirus B19 VP1u linked to scleroderma and aggravated dermal fibrosis.
Subject(s)
Parvoviridae Infections , Parvovirus B19, Human , Scleroderma, Systemic , Animals , Humans , Mice , Capsid Proteins/genetics , Fibrosis , Interleukin-6/metabolism , Matrix Metalloproteinase 9/metabolism , Parvoviridae Infections/complications , Parvovirus B19, Human/genetics , Scleroderma, Systemic/chemically induced , Tumor Necrosis Factor-alpha/metabolism , Viral ProteinsABSTRACT
BACKGROUND: Hyperactive neutrophil extracellular traps (NETs) formation plays a key role in the pathogenesis of severe COVID-19. Extracellular vesicles (EVs) are vehicles which carry cellular components for intercellular communication. The association between COVID-19 patients-derived EVs and NETs formation remains elusive. METHODS: We explored the roles of EVs in NETs formation from 40 COVID-19 patients with different disease severities as well as 30 healthy subjects. The EVs-carried microRNAs profile was analyzed using next generation sequencing approach which was validated by quantitative reverse transcription PCR. The regulatory mechanism of EVs on NETs formation was investigated by using an in vitro cell-based assay, including immunofluorescence assay, flow cytometry, and immunoblotting. RESULTS: COVID-19 patient-derived EVs induced NETs formation by endocytosis uptake. SARS-CoV-2 spike protein-triggered NETs formation was significantly enhanced in the presence of platelet-derived EVs (pEVs) and this effect was Toll-like receptor (TLR) 7/8- and NADPH oxidase-dependent. Increased levels of miR-21/let-7b were revealed in EVs from COVID-19 patients and were associated with disease severity. We demonstrated that the spike protein activated platelets directly, followed by the subsequent intracellular miR-21/let-7b upregulation and then were loaded into pEVs. The pEVs-carried miR-21 interacted with TLR7/8 to prime p47phox phosphorylation in neutrophils, resulting in NADPH oxidase activation to promote ROS production and NETs enhancement. In addition, miR-21 modulates NF-κB activation and IL-1ß/TNFα/IL-8 upregulation in neutrophils upon TLR7/8 engagement. The miR-21 inhibitor and TLR8 antagonist could suppress efficiently spike protein-induced NETs formation and pEVs primed NETs enhancement. CONCLUSIONS: We identified SARS-CoV-2 triggered platelets-derived GU-enriched miRNAs (e.g., miR-21/let-7b) as a TLR7/8 ligand that could activate neutrophils through EVs transmission. The miR-21-TLR8 axis could be used as a potential predisposing factor or therapeutic target for severe COVID-19.
Subject(s)
COVID-19 , Extracellular Traps , Extracellular Vesicles , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/pharmacology , Extracellular Traps/metabolism , SARS-CoV-2 , Toll-Like Receptor 7/metabolism , Toll-Like Receptor 8/metabolism , COVID-19/metabolism , NADPH Oxidases/metabolism , NADPH Oxidases/pharmacology , Extracellular Vesicles/metabolismABSTRACT
BACKGROUND: Patients with idiopathic inflammatory myopathy (IIM) often express a different type of myositis-specific autoantibodies (MSAs), each associated with different clinical symptoms. Understanding the immunopathogenesis of various IIM subgroups can help improve the diagnosis and prognosis of IIM patients with different MSAs. However, the immune cell profiles of these IIM patients with anti-aminoacyl tRNA synthetase (ARS) or anti-melanoma differentiation-associated gene 5 (MDA5) autoantibodies remain unclear. We focused on the immune cell profiles of IIM patients with anti-ARS or anti-MDA5 autoantibodies. RESULTS: The peripheral blood from IIM patients with anti-MDA5 autoantibody (MDA5 + group, n = 24) or one of the anti-ARS autoantibodies (ARS + group, n = 40) autoantibodies, and healthy controls (HC group, n = 60) were collected and examined. We found that IIM patients had a lower CD3 T cell population compared to the HC group. IIM patients showed a significantly lower TN cell population and a higher TEMRA cell population. Higher Th17 and Treg cell populations were found in these IIM patients than in the HC group. In these IIM patients, the MDA5 + group exhibited the higher percentages of Th17 and Treg cells than the ARS + group. It is noteworthy that the percentage of Th1 cells in the survival subgroup was higher than in the death subgroup in IIM patients with ARS + or MDA5 + . Furthermore, in the MDA5 + group, the percentage of Treg cells was higher in the survival subgroup compared to the death subgroup. CONCLUSIONS: Our study demonstrated that elevated Th1 may be a good prognostic indicator in IIM patients with ARS + or MDA5 + . Elevated Treg may also help predict a good prognosis in MDA5 + IIM patients. However, more large-scale studies and clinical samples are needed to verify the significance of Th1 and Treg cell subsets in clinical outcomes for these IIM patients with ARS + or MDA5 + . These data may help design a therapeutic approach that specifically targets the pathogenic immune molecular responsible for autoimmune attacks in IIM.
Subject(s)
Amino Acyl-tRNA Synthetases , Myositis , Humans , Autoantibodies , Myositis/diagnosis , Prognosis , Cell Differentiation , Retrospective StudiesABSTRACT
BACKGROUND: We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population. METHODS: We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images. RESULTS: In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease. CONCLUSION: Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients.
Subject(s)
Arthritis, Rheumatoid , Lung Diseases, Interstitial , Respiration Disorders , Humans , Adult , Oscillometry , Lung Diseases, Interstitial/diagnosis , Respiratory Function Tests , Arthritis, Rheumatoid/complicationsABSTRACT
Human parvovirus B19 (B19V) has been strongly associated with a variety of inflammatory disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease and systemic lupus erythematosus. Nonstructural protein 1 (NS1) of B19V has been demonstrated to play essential roles in the pathological processes of B19V infection due to its regulatory properties on inflammatory cytokines. Celastrol, a quinone methide isolated from Tripterygium wilfordii, has displayed substantial potential in treating inflammatory diseases, such as psoriasis and RA. However, little is known about the effects of celastrol on B19V NS1induced inflammation. Therefore, cell viability assay, migration assay, phagocytosis analysis, zymography assay, ELISA and immunoblotting were conducted to verify the influences of celastrol on macrophages. The present study reported the attenuating effects of celastrol on B19V NS1induced inflammatory responses in macrophages derived from human acute monocytic leukemia cell lines, U937 and THP1. Although the migration was not significantly decreased by celastrol in both U937 and THP1 macrophages, significantly decreased viability, migration and phagocytosis were detected in both B19V NS1activated U937 and THP1 macrophages in the presence of celastrol. Additionally, celastrol significantly decreased MMP9 activity and the levels of inflammatory cytokines, including IL6, TNFα and IL1ß, in B19V NS1activated U937 and THP1 cells. Notably, significantly decreased levels of NLR family pyrin domaincontaining 3, apoptosisassociated specklike, caspase1 and IL18 proteins were observed in both B19V NS1activated U937 and THP1 cells in the presence of celastrol, indicating the involvement of the inflammasome pathway. To the best of our knowledge, the present study is the first to report on the attenuating effects of celastrol on B19V NS1induced inflammatory responses in macrophages, suggesting a therapeutic role for celastrol in B19V NS1related inflammatory diseases.
Subject(s)
Arthritis, Rheumatoid , Parvovirus B19, Human , Humans , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Macrophages , CytokinesABSTRACT
OBJECTIVES: Monocyte distribution width (MDW) correlates with volume modifications of circulating monocytes upon activation. Given the crucial role of monocyte activation in the pathogenesis of adult-onset Still's disease (AOSD), we aimed to examine the associations between MDW and disease activity or inflammatory parameters in this disease. METHODS: In 58 AOSD patients and 95 other patients with coronavirus disease 2019 (COVID-19) as disease control, MDW and complete blood count were determined using a UniCel DxH800 analyser. C-reactive protein (CRP) levels were measured by nephelometry, and ferritin levels by chemiluminescent immunoassay. AOSD activity was assessed using a modified Pouchot score. RESULTS: MDW was significantly higher in active AOSD patients (median 28.3, interquartile range [IQR] 23.3-32.1) compared with inactive AOSD (19.2, IQR 18.0-20.6, p<0.001) or non-severe COVID-19 patients (23.2, IQR 21.0-25.2, p<0.01). MDW was positively correlated with AOSD activity scores, CRP, and ferritin levels (all p<0.001). Longitudinal follow-up evaluation revealed that median MDW significantly declined (28.3 versus 18.5, p<0.001) along with disease activity, paralleling a decrease in CRP and ferritin levels. Severe COVID-19 and sepsis patients had elevated MDW, which were not different from active AOSD patients. Multivariate analysis revealed MDW as a significant predictor of active AOSD, and MDW threshold at 21.7 could predict an active status with a high sensitivity of 91.3% and specificity of 94.3%. CONCLUSIONS: Elevated MDW and its positive correlation with inflammatory parameters in AOSD patients indicate MDW as a novel activity indicator, with a high MDW value above 21.7 linked to a high probability of active AOSD.