Neutrophil activation biomarker pentraxin 3 for diagnosis and monitoring of macrophage activation syndrome occurrence in adult-onset Still's disease.

Macrophage activation syndrome (MAS) is a potentially fatal consequence of adult-onset Still's disease (AOSD), driven by a cytokine storm. Efficient early diagnosis of AOSD-associated MAS requires a sensitive and specific biomarker. In this study, we demonstrated that pentraxin 3 (PTX3), an acute phase protein, was associated with AOSD disease activity and served as a biomarker for AOSD-MAS. PTX3 levels were significantly increased in AOSD patients compared to other autoimmune diseases and healthy controls. Plasma PTX3 levels showed positive correlations with inflammatory markers, the systemic score and the HScore. In active AOSD with MAS, PTX3 levels were higher compared to those in non-AOSD haemophagocytic lymphohistiocytosis (HLH) patients. Moreover, the PTX3's area under the curve value for distinguishing AOSD with MAS exceeded that of soluble interleukin-2 receptor, ferritin and C-reactive protein. Furthermore, plasma levels of PTX3 were associated with circulating NET-DNA levels. To fully understand the underlying mechanism of PTX3 prompting AOSD and AOSD-MAS progression, we discovered that neutrophils exhibited enhanced NET formation and mitogen-activated protein kinases (MAPK) pathway activation upon PTX3 stimulation. More importantly, PTX3-induced NET formation was effectively dampened by MAPK pathway inhibitors. These findings collectively revealed that PTX3 has a favorable correlation with disease activity and may serve as a potential biomarker to differentiate AOSD patients with MAS. Additionally, PTX3 induces NET release via the MAPK pathway, suggesting a pathogenic role in AOSD-MAS.

Characteristics of COVID-19 and Impact of Disease Activity in Patients with Adult-Onset Still's Disease.

INTRODUCTION: This study aimed to characterize the morbidity, hospitalization, and mortality rates among patients with adult-onset Still's disease (AOSD) affected by coronavirus disease 2019 (COVID-19) and explore the impact of COVID-19 on the disease activity of AOSD. METHODS: Data on the clinical and demographic characteristics, COVID-19-related symptoms, and outcomes were retrospectively collected. Patients were stratified according to COVID-19 severity and associations between risk factors and outcomes were analyzed using multivariate logistic regression. The disease activity of patients with AOSD flares after COVID-19 was described. RESULTS: A total of 188 patients with AOSD were followed up, of whom 75.5% (n = 142) had a confirmed or highly suspected COVID-19. Patients on medium or high-dose oral glucocorticoids or Janus kinase (JAK) inhibitors were at increased risk of developing moderate to severe COVID-19. Six patients suffered flares of AOSD following COVID-19 in a short period; however, the relapse rate was not statistically increased compared with patients without COVID-19. CONCLUSION: Patients with AOSD receiving medium or high-dose glucocorticoid therapy or JAK inhibitors had worse COVID-19 outcomes. Further work is needed to explore risk factors affecting COVID-19 outcomes and the impact of COVID-19 on disease activity in AOSD.

Neutralizing anti-IFN-γ IgG was increased in patients with systemic lupus erythematosus and associated with susceptibility to infection.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complicated autoimmune disease, in which infection is a leading cause of death. Some SLE patients clinically presented with recurrent and refractory infections, which manifested as adult-onset immunodeficiency syndrome due to the production of anti-interferon-γ (anti-IFN-γ) autoantibodies. This study aimed to investigate the role of anti-IFN-γ autoantibodies concerning severe infections in SLE patients. METHODS: We detected serum levels of anti-IFN-γ IgG/IgM isotypes in SLE patients with severe infections (n = 55), SLE patients without severe infections (n = 120), rheumatoid arthritis (n = 24), ankylosing spondylitis (n = 24), and healthy controls (n = 60). The relationship between anti-IFN-γ autoantibodies and clinical characteristics and laboratory parameters were analyzed. We further evaluated the neutralizing ability of anti-IFN-γ IgG. RESULTS: The level of anti-IFN-γ IgG was significantly elevated in SLE patients with severe infections compared with the other groups (all p < 0.01), and the positive rates of anti-IFN-γ IgG in SLE patients with and without severe infections were 29.1% and 10.8%, respectively. Further analysis indicated that the levels of anti-IFN-γ IgG were positively associated with the SLEDAI score (r = 0.6420, p < 0.001), and it could predict the susceptibility to severe infections in SLE patients. Moreover, the inhibition and function assay showed that purified IgG from anti-IFN-γ IgG-positive SLE patients could neutralize IFN-γ, and further impair IFN-γ-induced STAT1 phosphorylation. CONCLUSIONS: The neutralizing anti-IFN-γ IgG might increase the susceptibility to infection in SLE patients, which has important implications for the treatment. Key Points • The role of anti-IFN-γ autoantibodies concerning severe infections in SLE patients remains unknown. • The results of this study reveals that anti-IFN-γ IgG levels were significantly elevated in SLE patients with severe infections. • This study suggests that neutralizing anti-IFN-γ IgG might increase the susceptibility to infection in SLE patients.

Neutrophil extracellular trap-induced intermediate monocytes trigger macrophage activation syndrome in adult-onset Still's disease.

BACKGROUND: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disease characterized by innate immune system activation, with a high risk for macrophage activation syndrome (MAS). MAS development is associated with monocyte/macrophage activation and cytokine storm. Monocytes consist of three different subsets, classical monocytes (CMs, CD14brightCD16 -), intermediate monocytes (IMs, CD14brightCD16 +), and non-classical monocytes (NCMs, CD14dimCD16 +), each has distinct roles in inflammatory regulation. However, the frequencies and regulatory mechanism of monocyte subsets in AOSD patients have not been identified. METHODS: We performed flow cytometry, RNA sequencing, phagocytosis analysis, and enzyme-linked immunosorbent assay to evaluate monocyte subsets, cell functions, and potential biomarkers. The effect of neutrophil extracellular traps (NETs) on monocytes was determined by evaluating mRNA levels of DNA sensors, surface CD16 expression, and inflammasome pathway activation. RESULTS: Higher proportions of intermediate monocytes (IMs) were identified in active AOSD patients. IMs displayed higher expression of CD80, CD86, HLA-DR, and CD163 than CMs and NCMs. CD163 upregulation was noted on AOSD IMs, accompanied by increased phagocytic activity and elevated cytokine/chemokine production, including IL-1ß, IL-6, CCL8, and CXCL10. The frequencies of IMs were correlated with disease activity and higher in AOSD patients with MAS (AOSD-MAS). CCL8 and CXCL10 were highly expressed in RNA sequencing of monocytes from AOSD-MAS patients and plasma CXCL10 level could serve as a potential biomarker for AOSD-MAS. Moreover, DNA-sensing pathway was activated in monocytes from AOSD-MAS patients. Stimulation with NETs derived from AOSD induced DNA sensor expression, the expansion of IMs, and inflammasome pathway activation. These effects can be abrogated by DNase I treatment. CONCLUSIONS: Our results demonstrated that the proportions of IMs were elevated in AOSD and associated with MAS. The DNA component in NETs from AOSD plays an important role in the formation of IMs, shedding new light for the therapeutic target.

The use of high-sensitivity cardiac troponin I in assessing cardiac involvement and Disease prognosis in idiopathic inflammatory myopathy.

OBJECTIVES: Cardiac involvement is one of the most serious complications of idiopathic inflammatory myopathy (IIM) that indicates poor prognosis. However, there is a lack of effective biomarkers for the identification of cardiac involvement and the prediction of prognosis in IIM. Here, we aimed to explore the value of different cardiac biomarkers in IIM patients. METHODS: A total of 142 IIM patients in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2019 to October 2022 were included in this study. The clinical characteristics, laboratory tests, treatments and prognosis were recorded. The disease activity was assessed according to the core set measures. The correlations of the serum cardiac biomarkers levels with disease activity were analyzed by the Spearman correlation test. Risk factors for cardiac involvement were evaluated by multivariate logistic regression analysis. RESULTS: Higher high-sensitivity cardiac troponin I (hs-cTnI) levels were associated with cardiac involvement (n = 41) in IIM patients [adjusted OR 7.810 (95% CI: 1.962-31.097); p = 0.004], independent of other serum cardiac biomarkers. The abnormal hs-cTnI had the highest AUC for distinguishing of cardiac involvement in IIM patients (AUC = 0.848, 95% CI: 0.772,0.924; p < 0.001). Besides, we found that high serum levels of hs-cTnI were significantly correlated with disease activity. Moreover, patients with higher serum levels of hs-cTnI tended to suffer from poor prognosis. CONCLUSIONS: Serum hs-cTnI testing may play a role in screening for cardiac involvement in IIM patients. Abnormal levels of serum hs-cTnI were associated with increased disease activity and poor prognosis.

Risk factors in antiphospholipid antibody-associated valvular heart disease: A 383-patient cohort study.

Valvular heart disease (VHD) is a prevalent cardiac manifestation in antiphospholipid syndrome (APS) patients. However, risk factors and predictors for antiphospholipid antibody-associated VHD (aPL-VHD) remain vague. We aimed to assess the risk of developing aPL-VHD in aPL-positive patients, by establishing a clinical prediction model upon a cross-sectional cohort from APS-Shanghai database, including 383 APS patients and durable aPL carriers with transthoracic echocardiography investigation. The prevalence of aPL-VHD was 11.5%. Multivariate logistic regression analysis identified three independent risk factors for aPL-VHD: anti-ß2GPI IgG (OR 5.970, P < 0.001), arterial thrombosis (OR 2.758, P = 0.007), and stratified estimated glomerular filtration rate levels (OR 0.534, P = 0.001). A prediction model for aPL-VHD, incorporating the three factors, was further developed, which demonstrated good discrimination with a C-index of 0.855 and 0.841 (after bootstrapping), and excellent calibration (P = 0.790). We provide a practical tool for assessing the risk of developing VHD among aPL-positive patients.

The landscape of innate and adaptive immune cell subsets in patients with adult-onset Still's disease.

OBJECTIVE: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder. The understanding of the changes in adaptive immune cells and the crosstalk between innate and adaptive immune systems in AOSD is limited. This study aimed to examine the peripheral immune cell composition and inflammatory protein levels in AOSD patients. METHODS: Twenty-nine active AOSD patients were enrolled. Flow cytometry was used to analyze the cell populations in peripheral blood. Antibody chips were utilized to detect the protein expression profile in serum. RESULTS: In active AOSD patients, there was an increase in the percentage of classical and non-classical monocytes among peripheral blood mononuclear cells. The proportion of natural killer (NK) cells decreased, with an increase in CD56dim NK1 cells and a decrease in CD56bright NK2 cells compared with healthy controls (HC). The percentage of naïve central memory T cells was decreased, while the percentage of effector and effector memory T cells was increased among adaptive lymphocytes. The proportion of naïve B and memory B cells was decreased, while plasma cells were increased in AOSD patients, indicating activation of the adaptive immune system. Additionally, the serum levels of 40 proteins were elevated in AOSD patients, primarily involved in cytokine-cytokine receptor interaction, inflammatory response, and regulation of MAPK cascade. CONCLUSION: Our findings showed the activation of the innate and adaptive immune system in AOSD. The protein-protein interaction analysis suggested potential communication between innate and adaptive cell subsets. These findings provide new insights into the pathogenesis of the disease and the development of targeted therapies.

CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis.

Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19.

Value of the HFA-PEFF diagnostic algorithms for heart failure with preserved ejection fraction to the inflammatory myopathy population.

OBJECTIVES: The HFA-PEFF score has been validated to hold great diagnostic and prognostic utility for heart failure with preserved ejection fraction (HFpEF). Idiopathic inflammatory myopathy (IIM) is recognized as one of the potential etiologies underlying HFpEF. Here, we intended to investigate the real prevalence of HFpEF in IIM via the HFA-PEFF score and explore the prognostic value of this score. METHODS: Two hundred twenty IIM patients were enrolled for assessment. The cohort was divided into low, intermediate and high tertiles of the HFA-PEFF score. Spearman's correlation analysis was used to explore the association between the score and disease activity. Chi-square test was applied to investigate the distribution discrepancy of HFA-PEFF tertiles among patients with different myositis-specific antibodies (MSAs) or myositis-associated antibodies (MAAs). Univariate and multivariate ordinal regression analyses were performed to screen risk factors for high HFA-PEFF scores. Survival curves were obtained using the Kaplan-Meier method and log-rank tests. RESULTS: In total, 79 (35.9%), 107 (48.6%) and 34 (15.5%) patients were rated low, intermediate and high probability of HFpEF, respectively. The HFA-PEFF score correlated well with disease activity. Patients with positive AMA-M2 scored higher in the HFA-PEFF score (p = 0.011). During follow-up, patients with positive AMA-M2 or anti-SRP antibody developed an inclination towards concentric hypertrophy on echocardiography. Additionally, palpitation symptom, AMA-M2 positivity and elevated serum levels of LDH, cTnI were independent risk factors for high HFA-PEFF scores. Finally, a high-tertile HFA-PEFF score was related to lower overall survival rate (p < 0.001). Patients with positive AMA-M2 had poorer outcomes (p = 0.002). CONCLUSION: HFpEF was prevailing in IIM patients according to the HFA-PEFF score. The HFA-PEFF score correlated well with disease activity and held significant prognostic value. Patients with AMA-M2 antibody were prone to have poor outcomes.

Activation of Platelet mTORC2/Akt Pathway by Anti-ß2GP1 Antibody Promotes Thrombosis in Antiphospholipid Syndrome.

BACKGROUND: Anti-ß2GP1 (ß2-glycoprotein 1) antibodies are the primary pathogenic antibody to promote thrombosis in antiphospholipid syndrome (APS), yet the underlying mechanism remains obscure. We aimed to explore the intracellular pathway that mediated platelet activation. METHODS: Platelets were isolated from patients with APS and subjected to RNA sequencing. Platelet aggregation, the release of platelet granules, platelet spreading, and clot retraction were detected to evaluate platelet activation. We purified anti-ß2GP1 antibodies from patients with APS and the total IgG from healthy donors to stimulate platelets with/without FcγRIIA (Fcγ receptor IIA) blocking antibody or Akt (protein kinase B) inhibitor. Platelet-specific Sin1 (stress-activated protein kinase-interacting protein) deficiency mice were established. The thrombus model of inferior vena cava flow restriction, ferric chloride-induced carotid injury model, and laser-induced vessel wall injury in cremaster arterioles model were constructed after administration of anti-ß2GP1 antibodies. RESULTS: Combined RNA sequencing and bioinformatics analysis suggested that APS platelets exhibited increased levels of mRNA associated with platelet activation, which was in line with the hyperactivation of APS platelets in response to stimuli. Platelet activation in APS platelets was accompanied by upregulation of the mTORC2 (mammalian target of the rapamycin complex 2)/Akt pathway and increased levels of SIN1 phosphorylation at threonine 86. Anti-ß2GP1 antibody derived from patients with APS enhanced platelet activation and upregulated the mTORC2/Akt pathway. Moreover, the Akt inhibitor weakened the potentiating effect of the anti-ß2GP1 antibody on platelet activation. Notably, Sin1 deficiency suppresses anti-ß2GP1 antibody-enhanced platelet activation in vitro and thrombosis in all 3 models. CONCLUSIONS: This study elucidated the novel mechanism involving the mTORC2/Akt pathway, which mediates the promotion of platelet activation and induction of thrombosis by the anti-ß2GP1 antibody. The findings suggest that SIN1 may be a promising therapeutic target for the treatment of APS.

Identification of Distinct Genetic Profiles of Palindromic Rheumatism Using Whole-Exome Sequencing.

OBJECTIVE: Previous studies have underlined the genetic susceptibility in the pathogenesis of palindromic rheumatism (PR), but the known PR loci only partially explain the disease's genetic background. We aimed to genetically identify PR by whole-exome sequencing (WES). METHODS: This multicenter prospective study was conducted in 10 Chinese specialized rheumatology centers between September 2015 and January 2020. WES was performed in 185 patients with PR and in 272 healthy controls. PR patients were divided into PR subgroups who were negative for anti-citrullinated protein antibody (ACPA-) and positive for ACPA (ACPA+) according to ACPA titer (cutoff value 20 IU/liter). We conducted whole-exome association analysis for the WES data. We used HLA imputation to type HLA genes. In addition, we used the polygenic risk score to measure the genetic correlations between PR and rheumatoid arthritis (RA) and the genetic correlations between ACPA- PR and ACPA+ PR. RESULTS: Among 185 patients with PR enrolled in our study, 50 patients (27.02%) were ACPA+ and 135 PR patients (72.98%) were ACPA-. We identified 8 novel loci (in the ACPA- PR group: ZNF503, RPS6KL1, HOMER3, HLA-DRA; in the ACPA+ PR group: RPS6KL1, TNPO2, WASH2P, FANK1) and 3 HLA alleles (in the ACPA- PR group: HLA-DRB1*0803 and HLA-DQB1; in the ACPA+ PR group: HLA-DPA1*0401) that were associated with PR and that surpassed genome-wide significance (P < 5 × 10-8 ). Furthermore, polygenic risk score analysis showed that PR and RA were not similar (R2 < 0.025), whereas ACPA+ PR and ACPA- PR showed a moderate genetic correlation (0.38 < R2 < 0.8). CONCLUSION: This study demonstrated the distinct genetic background between ACPA- and ACPA+ PR patients. Additionally, our findings strengthened that PR and RA were not genetically similar.

Continuation, reduction, or withdrawal of tofacitinib in patients with rheumatoid arthritis achieving sustained disease control: a multicenter, open-label, randomized controlled trial.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION: Chictr.org, ChiCTR2000039799.

Differential diagnostic performance of PET/CT in adult-onset still's disease and lymphoma: a retrospective pilot study.

Background: Adult-onset still's disease (AOSD) and lymphoma are the common causes of fever of unknown origin (FUO) and show some similar clinical symptoms. This study aimed to establish a reliable and easy-to-used scoring model based on clinical information, laboratory characteristics and 18F-fluorodeoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) images for the differential diagnosis of these two diseases. Methods: A development cohort including 70 AOSD and 37 lymphoma patients was used to establish a scoring model based on the features of PET/CT images. The scoring model was then validated in a validation cohort of 15 AOSD and 12 lymphoma patients. The features of involved bone marrow, spleen, lymph nodes, and other organs or tissues displayed on PET/CT images were compared. Multiple logistics regression and decision tree analysis were used to establish the scoring model. Results: Four features that could significantly differentiate these two diseases were selected to establish a scoring model discriminating AOSD from lymphoma, including (I) white blood cell (WBC) count ≤10×109/L (1 point); (II) ferritin ≤ upper limit of normal (ULN) (1 point); (III) no abnormal bone marrow metabolism (1 point); (IV) total lesion glycolysistotal (TLGtotal) >9.0 (1 point). After decision tree analysis, it showed that a score ≤1 indicates AOSD. A score ≥3 strongly suggested lymphoma, with a sensitivity of 81.1% and specificity of 90.0% in the development cohort, and a sensitivity of 58.3% and specificity of 100% in the validation cohort. Conclusions: Our scoring model showed good diagnosis performance in distinguishing AOSD from lymphoma.

Inactivated SARS-CoV-2 vaccine does not increase the risk of relapse in patients with clinically inactive adult-onset Still's disease.

OBJECTIVE: A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. METHODS: We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBP-CorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period, and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. RESULTS: A total of 122 patients with inactive AOSD were included, of which 49.2% (n = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% vs 6.8%), and no relapse occurred within 1 month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. CONCLUSION: Increased disease activity or relapse following vaccination with inactivated SARS-CoV-2 was rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS-CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2.

COVID-19 vaccine affects neither prothrombotic antibody profile nor thrombosis in primary anti-phospholipid syndrome: a prospective study.

OBJECTIVE: To explore whether inactivated coronavirus disease 2019 vaccine influences the profile of prothrombotic autoantibodies and induces thrombotic events in primary APS patients. METHODS: We enrolled 39 primary APS patients who received two doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BBIBPCorV, Sinopharm, Beijing, China) voluntarily in this prospective cohort. Prothrombotic autoantibodies were determined before vaccination and 4 weeks after the second dose of vaccination. Thrombotic disorders were evaluated via hospital site visits and assessments. RESULTS: There was no significant difference in the presence of all 11 autoantibodies detected before and 4 weeks after vaccination: for aCL, IgG (14 vs 16, P = 0.64), IgM (13 vs 19, P = 0.34), IgA (2 vs 3, P = 0.64); anti-ß2GP1, IgG (12 vs 12, P = 1.00), IgM (5 vs 8, P = 0.36), IgA (4 vs 3, P = 0.69); anti-PS/PT IgG (13 vs 16, P = 0.48), IgM (17 vs 22, P = 0.26); LAC (22 vs 28, P = 0.16); aPF4-heparin (0 vs 0, P = 1.00) and ANA (23 vs 26, P = 0.48). Notably, the distribution of the aPL profile in the pre- and post-vaccination cohorts was not affected by SARS-CoV-2 vaccination: for patients with a low-risk aPL profile (11 vs 10, P = 0.799) and patients with a high-risk aPL profile (28 vs 29, P = 0.799), respectively. Furthermore, no case exhibited symptoms of the thrombotic disorder during a minimum follow-up period of 12 weeks. There was no adjustment to the ongoing treatment regimens following SARS-CoV-2 vaccination. CONCLUSION: Inactivated SARS-CoV-2 vaccine does not influence the profile of anti-phospholipid antibodies and anti-PF4-heparin antibodies nor induces thrombotic events in primary APS patients.

Performance of the modified Systemic Manifestation Score for systemic juvenile idiopathic arthritis in Adult-onset Still's disease.

OBJECTIVES: To compare the ability of the modified Systemic Manifestation Score (mSMS) and the mPouchot score to distinguish adult-onset Still's disease (AOSD) with high disease severity in a large cohort. METHODS: We scored the disease severity of 174 patients and categorized them into high and low disease severity states. The correlation of mSMS and mPouchot score with ESR, CRP, ferritin, liver function tests, and serum cytokines was investigated. Receiver operator characteristic (ROC) curve and logistic regression analysis were performed to compare the ability of mSMS and mPouchot to distinguish patients with severe AOSD. RESULTS: Both mSMS and mPouchot score were positively correlated with ESR (both P < 0.001), CRP (both P < 0.0001), and serum ferritin (both P < 0.0001). Moreover, both mSMS and mPouchot score are significantly associated with liver dysfunction and high IL-18 (both P < 0.0001) and IL-6 (both P < 0.01) levels in AOSD patients. Furthermore, the area under curve (AUC) value of mSMS was significantly less than of mPouchot score (0.71 for mSMS, 0.81 for mPouchot score, P < 0.0001). Compared with mPouchot score, mSMS had higher sensitivity (75.64% vs 74.36%) and lower specificity (55.06% vs 76.40%). And mSMS had a worse performance in assessing high disease severity than mPouchot score in logistic analysis. CONCLUSION: Both scores are proven as effective to assess disease severity of AOSD. By contrast, mSMS perform worse in assessing high disease severity of AOSD patients than mPouchot score. Key Points • Both modified Systemic Manifestation Score (mSMS) and modified Pouchot score (mPouchot score) positively correlated with ESR, CRP, and serum ferritin of AOSD patients. • Both scores are significantly associated with impaired liver function and high serum cytokine levels. • mSMS had lower discriminative ability than mPouchot score to distinguish high disease severity of AOSD patients.

The use of high-sensitivity cardiac troponin I in assessing cardiac involvement and Disease prognosis in idiopathic inflammatory myopathy

Abstract Objectives Cardiac involvement is one of the most serious complications of idiopathic inflammatory myopathy (IIM) that indicates poor prognosis. However, there is a lack of effective biomarkers for the identification of cardiac involvement and the prediction of prognosis in IIM. Here, we aimed to explore the value of different cardiac biomarkers in IIM patients. Methods A total of 142 IIM patients in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2019 to October 2022 were included in this study. The clinical characteristics, laboratory tests, treatments and prognosis were recorded. The disease activity was assessed according to the core set measures. The correlations of the serum cardiac biomarkers levels with disease activity were analyzed by the Spearman correlation test. Risk factors for cardiac involvement were evaluated by multivariate logistic regression analysis. Results Higher high-sensitivity cardiac troponin I (hs-cTnI) levels were associated with cardiac involvement (n = 41) in IIM patients [adjusted OR 7.810 (95% CI: 1.962-31.097); p = 0.004], independent of other serum cardiac biomarkers. The abnormal hs-cTnI had the highest AUC for distinguishing of cardiac involvement in IIM patients (AUC = 0.848, 95% CI: 0.772,0.924; p < 0.001). Besides, we found that high serum levels of hs-cTnI were significantly correlated with disease activity. Moreover, patients with higher serum levels of hs-cTnI tended to suffer from poor prognosis. Conclusions Serum hs-cTnI testing may play a role in screening for cardiac involvement in IIM patients. Abnormal levels of serum hs-cTnI were associated with increased disease activity and poor prognosis. Key Points Among all the cardiac biomarkers, the serum levels of hs-cTnI were independently associated with cardiac involvement in IIM patients. The serum levels of hs-cTnI were significantly correlated with disease activity in IIM patients. The abnormal hs-cTnI levels were correlated with poor prognosis in IIM patients.

Ferritin triggers neutrophil extracellular trap-mediated cytokine storm through Msr1 contributing to adult-onset Still's disease pathogenesis.

Hyperferritinemic syndrome, an overwhelming inflammatory condition, is characterized by high ferritin levels, systemic inflammation and multi-organ dysfunction, but the pathogenic role of ferritin remains largely unknown. Here we show in an animal model that ferritin administration leads to systemic and hepatic inflammation characterized by excessive neutrophil leukocyte infiltration and neutrophil extracellular trap (NET) formation in the liver tissue. Ferritin-induced NET formation depends on the expression of peptidylarginine deiminase 4 and neutrophil elastase and on reactive oxygen species production. Mechanistically, ferritin exposure increases both overall and cell surface expression of Msr1 on neutrophil leukocytes, and also acts as ligand to Msr1 to trigger the NET formation pathway. Depletion of neutrophil leukocytes or ablation of Msr1 protect mice from tissue damage and the hyperinflammatory response, which further confirms the role of Msr1 as ferritin receptor. The relevance of the animal model is underscored by the observation that enhanced NET formation, increased Msr1 expression and signalling on neutrophil leukocytes are also characteristic to adult-onset Still's disease (AOSD), a typical hyperferritinemic syndrome. Collectively, our findings demonstrate an essential role of ferritin in NET-mediated cytokine storm, and suggest that targeting NETs or Msr1 may benefit AOSD patients.