The additional role of anti-nucleosome antibodies in the prediction of renal damage in systemic lupus erythematosus based on CSTAR (XXV).

OBJECTIVES: The predominant determinant of an unfavorable prognosis among Systemic Lupus Erythematosus (SLE) patients resides in the irreversible organ damage. This prospective cohort study aimed to identify the additional value of anti-nucleosome antibodies on organ damage accumulation in SLE patients. METHODS: Based on the Chinese SLE Treatment and Research group (CSTAR) registry, demographic characteristics, autoantibodies profiles, and clinical manifestations were collected at baseline. Follow-up data were collected by reviewing clinical records. RESULTS: Of 2481 SLE patients with full follow-up data, 663 (26.7%) were anti-nucleosome antibodies positive and 1668 (68.0%) were anti-dsDNA antibodies positive. 764 (30.8%) patients developed new organ damage during a mean follow-up of 4.31 ± 2.60 years. At baseline, patients with positive anti-nucleosome antibodies have a higher rate of lupus nephritis (50.7% vs 36.2%, p < .001). According to the multivariable Cox regression analysis, both anti-nucleosome (HR = 1.30, 95% CI, 1.09-1.54, p < .001) and anti-dsDNA antibodies (HR=1.68, 95% CI, 1.38-2.05, p < .001) were associated with organ damage accumulation. Anti-nucleosome (HR = 2.51, 95% CI, 1.81-3.46, p < .001) and anti-dsDNA antibodies (HR = 1.69, 95% CI, 1.39-2.06, p < .001) were independent predictors for renal damage. Furthermore, the combination of the two antibodies can provide more accurate information about renal damage in overall SLE patients (HR = 3.19, 95% CI, 2.49-4.10, p < .001) and patients with lupus nephritis at baseline (HR = 2.86, 95% CI, 2.29-3.57, p < .001). CONCLUSION: Besides anti-dsDNA antibodies, anti-nucleosome antibodies can also provide information about organ damage accrual during follow-up. The ability of co-positivity of anti-nucleosome and anti-dsDNA antibodies in predicting renal damage may lead to additional benefits in the follow-up of these patients.

Exploring the impact of acute viral exposure on clinical characteristics and antibody profiles in antiphospholipid syndrome: a study in CAPSTONE.

The relationship between antiphospholipid syndrome (APS) and acute viral infection, such as SARS-CoV-2, is unclear. This study aims to assess symptoms, antiphospholipid antibody (aPL) fluctuations, and complication risks in APS patients infected with SARS-CoV-2. APS patients from Peking Union Medical College Hospital during the COVID-19 outbreak (October-December 2022) were included. Age- and gender-matched APS patients without infection served as controls. Data on demographics, symptoms, treatments, and serum aPL levels were analyzed. Of 234 APS patients, 107 (45.7%) were infected with SARS-CoV-2. Typical symptoms included high fever (81.3%), cough/expectoration (70.1%), and pharyngalgia (52.3%). Age- and gender-based matching selected 97 patients in either infected or uninfected group. After infection, anti-ß-2-glycoprotein I-IgG (aß2GP1-IgG) increased from 4.14 to 4.18 AU/ml, aß2GP1-IgM decreased from 9.85 to 7.38 AU/ml, and anticardiolipin-IgA (aCL-IgA) significantly increased with a median remaining at 2.50 APLU/ml. Lupus anticoagulants and other aPLs remained stable. Arterial thrombosis incidence increased from 18 (18.6%) to 21 (21.6%), while venous thrombosis incidence did not change. Additionally, 7 (6.5%) patients presented either new-onset or worsening thrombocytopenia, characterized by a significant decline in platelet count (no less than 10 × 109/L) within two weeks of SARS-CoV-2 infection, all of which recovered within 2 weeks. Acute SARS-CoV-2 infection may induce or worsen thrombocytopenia but does not substantially increase thrombotic events in APS. The process of SARS-CoV-2 infection was related to mild titer fluctuation of aß2GP1-IgG, aß2GP1-IgM and aCL-IgA in APS patients, necessitating careful monitoring and management.

A Glimpse into Humoral Response and Related Therapeutic Approaches of Takayasu's Arteritis.

Takayasu's arteritis (TAK) manifests as an insidiously progressive and debilitating form of granulomatous inflammation including the aorta and its major branches. The precise etiology of TAK remains elusive, with current understanding suggesting an autoimmune origin primarily driven by T cells. Notably, a growing body of evidence bears testimony to the widespread effects of B cells on disease pathogenesis and progression. Distinct alterations in peripheral B cell subsets have been described in individuals with TAK. Advancements in technology have facilitated the identification of novel autoantibodies in TAK. Moreover, emerging data suggest that dysregulated signaling cascades downstream of B cell receptor families, including interactions with innate pattern recognition receptors such as toll-like receptors, as well as co-stimulatory molecules like CD40, CD80 and CD86, may result in the selection and proliferation of autoreactive B cell clones in TAK. Additionally, ectopic lymphoid neogenesis within the aortic wall of TAK patients exhibits functional characteristics. In recent decades, therapeutic interventions targeting B cells, notably utilizing the anti-CD20 monoclonal antibody rituximab, have demonstrated efficacy in TAK. Despite the importance of the humoral immune response, a systematic understanding of how autoreactive B cells contribute to the pathogenic process is still lacking. This review provides a comprehensive overview of the biological significance of B cell-mediated autoimmunity in TAK pathogenesis, as well as insights into therapeutic strategies targeting the humoral response. Furthermore, it examines the roles of T-helper and T follicular helper cells in humoral immunity and their potential contributions to disease mechanisms. We believe that further identification of the pathogenic role of autoimmune B cells and the underlying regulation system will lead to deeper personalized management of TAK patients. We believe that further elucidation of the pathogenic role of autoimmune B cells and the underlying regulatory mechanisms holds promise for the development of personalized approaches to managing TAK patients.

Efficacy and Safety of Upadacitinib or Elsubrutinib Alone or in Combination for Systemic Lupus Erythematosus: A Phase 2 Randomized Controlled Trial.

OBJECTIVE: The 48-week, phase 2 SLEek study (NCT03978520) evaluated the efficacy and safety of upadacitinib (Janus kinase inhibitor) and elsubrutinib (Bruton's tyrosine kinase inhibitor) alone or in combination (ABBV-599) in adults with moderately to severely active systemic lupus erythematosus (SLE). METHODS: Patients were randomized 1:1:1:1:1 to once-daily (QD) ABBV-599 high dose (HD; elsubrutinib 60mg + upadacitinib 30mg), ABBV-599 low dose (LD; elsubrutinib 60mg + upadacitinib 15mg), elsubrutinib 60mg, upadacitinib 30mg, or placebo. The primary endpoint was the proportion of patients achieving both SLE Responder Index-4 (SRI-4) and glucocorticoid dose ≤10mg QD at week 24. Additional assessments through week 48 included British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) and Lupus Low Disease Activity State (LLDAS) responses, number of flares, time to first flare, and adverse events. RESULTS: The study enrolled 341 patients. The ABBV-599LD and elsubrutinib arms were discontinued after a planned interim analysis showed lack of efficacy (no safety concerns). More patients achieved the primary endpoint with upadacitinib (54.8%; P=0.028) and ABBV-599HD (48.5%; P=0.081) versus placebo (37.3%). SRI-4, BICLA, and LLDAS response rates were higher for both upadacitinib and ABBV-599HD versus placebo at weeks 24 and 48. Flares were reduced and time to first flare through week 48 was substantially delayed with both upadacitinib and ABBV-599HD versus placebo. No new safety signals were observed beyond those previously reported for upadacitinib or elsubrutinib. CONCLUSIONS: Upadacitinib 30mg alone or in combination with elsubrutinib (ABBV-599HD) demonstrated significant improvements in SLE disease activity, reduced flares and were well tolerated through 48 weeks.

Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu's arteritis.

OBJECTIVES: Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK. METHODS: VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments. RESULTS: Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients. CONCLUSIONS: VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.

S100a8/9 (S100 Calcium Binding Protein a8/9) Promotes Cardiac Hypertrophy Via Upregulation of FGF23 (Fibroblast Growth Factor 23) in Mice.

BACKGROUND: S100a8/9 (S100 calcium binding protein a8/9) belongs to the S100 family and has gained a lot of interest as a critical regulator of inflammatory response. Our previous study found that S100a8/9 homolog promoted aortic valve sclerosis in mice with chronic kidney disease. However, the role of S100a8/9 in pressure overload-induced cardiac hypertrophy remains unclear. The present study was to explore the role of S100a8/9 in cardiac hypertrophy. METHODS AND RESULTS: Cardiomyocyte-specific S100a9 loss or gain of function was achieved using an adeno-associated virus system, and the model of cardiac hypertrophy was established by aortic banding-induced pressure overload. The results indicate that S100a8/9 expression was increased in response to pressure overload. S100a9 deficiency alleviated pressure overload-induced hypertrophic response, whereas S100a9 overexpression accelerated cardiac hypertrophy. S100a9-overexpressed mice showed increased FGF23 (fibroblast growth factor 23) expression in the hearts after exposure to pressure overload, which activated calcineurin/NFAT (nuclear factor of activated T cells) signaling in cardiac myocytes and thus promoted hypertrophic response. A specific antibody that blocks FGFR4 (FGF receptor 4) largely abolished the prohypertrophic response of S100a9 in mice. CONCLUSIONS: In conclusion, S100a8/9 promoted the development of cardiac hypertrophy in mice. Targeting S100a8/9 may be a promising therapeutic approach to treat cardiac hypertrophy.

Comparison of clinical characteristics between patients with axial spondyloarthritis with and without acute anterior uveitis: a multicentre study of the Chinese Spondyloarthritis Registry.

OBJECTIVES: This study explores the clinical characteristics associated with the occurrence of acute anterior uveitis (AAU) in patients with axial spondyloarthritis (axSpA) within a large, multicentre database. METHODS: This observational, cross-sectional study of patients with axSpA used data from the Chinese Spondyloarthritis Registry between August 1, 2018, and March 31, 2020. The demographic and clinical features of patients with and without AAU were compared. Univariate and multivariate analyses were performed to determine the association between variables and uveitis. RESULTS: A total of 4304 patients were included in this study. The prevalence of AAU in patients with axSpA was 10.59%. Multivariate logistic regression analysis revealed a positive correlation between AAU and age at diagnosis (odds ratio [OR], 1.026; p<0.001), disease duration (OR, 2.117; p<0.001), current or past Achilles tendinitis (OR, 1.692; p<0.001), current or past dactylitis (OR, 1.687; p=0.002), current or past psoriasis (OR, 3.932; p<0.001), presence of human leukocyte antigen-B27 (HLA-B27) (OR, 2.787; p<0.001), and a good response to non-steroidal anti-inflammatory drugs (NSAIDs) (OR, 1.343; p=0.027). CONCLUSIONS: AAU was the most common extra-articular manifestation in the Chinese Spondyloarthritis Registry. In Chinese patients with axSpA, older age at diagnosis, longer disease duration, presence of HLA-B27, current or past Achilles tendinitis, current or past dactylitis, current or past psoriasis, and a good response to NSAIDs were positively associated with AAU.

Changes in serum immunoglobulin G glycosylation patterns for antiphospholipid syndrome patients with lectin microarray.

Antiphospholipid syndrome is a rare autoimmune disease characterized by persistent antiphospholipid antibodies. Immunoglobulin G plays a vital role in disease progression, with its structure and function affected by glycosylation. We aimed to investigate the changes in the serum immunoglobulin G glycosylation pattern in antiphospholipid syndrome patients. We applied lectin microarray on samples from 178 antiphospholipid syndrome patients, 135 disease controls (including Takayasu arteritis, rheumatoid arthritis and cardiovascular disease) and 100 healthy controls. Lectin blots were performed for validation of significant differences. Here, we show an increased immunoglobulin G-binding level of soybean agglutinin (p = 0.047, preferring N-acetylgalactosamine) in antiphospholipid syndrome patients compared with healthy and disease controls. Additionally, the immunoglobulin G from antiphospholipid syndrome patients diagnosed with pregnancy events had lower levels of fucosylation (p = 0.001, recognized by Lotus tetragonolobus) and sialylation (p = 0.030, recognized by Sambucus nigra I) than those with simple thrombotic events. These results suggest the unique serum immunoglobulin G glycosylation profile of antiphospholipid syndrome patients, which may inform future studies to design biomarkers for more accurate diagnosis of antiphospholipid syndrome and even for the prediction of clinical symptoms in patients.

The prognosis and management of reclassified systemic lupus erythematosus associated pulmonary arterial hypertension according to 2022 ESC/ERS guidelines.

BACKGROUND AND AIMS: The 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guideline has recently revised the hemodynamic definition of pulmonary arterial hypertension. However, there is currently limited research on the prognosis and treatment of system lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH) patients that have been reclassified by the new hemodynamic definition. This study aims to analyze the prognosis of newly reclassified SLE-PAH patients and provide recommendations for the management strategy. METHODS: This retrospective study analyzed records of 236 SLE-PAH patients who visited Peking Union Medical College Hospital (PUMCH) from 2011 to 2023, among whom 22 patients were reclassified into mild SLE-PAH (mean pulmonary arterial pressure (mPAP) of 21-24 mmHg, pulmonary vascular resistance (PVR) of 2-3 WU, and PAWP ≤ 15 mmHg) according to the guidelines and 14 were defined as unclassified SLE-PAH patients (mPAP 21-24 mmHg and PVR ≤ 2 WU). The prognosis was compared among mild SLE-PAH, unclassified SLE-PH, and conventional SLE-PAH patients (mPAP ≥ 25 mmHg and PVR > 3WU). Besides, the effectiveness of pulmonary arterial hypertension (PAH)-specific therapy was evaluated in mild SLE-PAH patients. RESULTS: Those mild SLE-PAH patients had significantly longer progression-free time than the conventional SLE-PAH patients. Among the mild SLE-PAH patients, 4 did not receive PAH-specific therapy and had a similar prognosis as patients not receiving specific therapy. CONCLUSIONS: This study supports the revised hemodynamic definition of SLE-PAH in the 2022 ESC/ERS guideline. Those mild and unclassified SLE-PH patients had a better prognosis, demonstrating the possibility and significance of early diagnosis and intervention for SLE-PAH. This study also proposed a hypothesis that IIT against SLE might be sufficient for those reclassified SLE-PAH patients.

Identification of the circRNA-miRNA-mRNA network for treating methamphetamine-induced relapse and behavioral sensitization with cannabidiol.

AIMS: This study aims to investigate the pharmacological effects and the underlying mechanism of cannabidiol (CBD) on methamphetamine (METH)-induced relapse and behavioral sensitization in male mice. METHODS: The conditioned place preference (CPP) test with a biased paradigm and open-field test were used to assess the effects of CBD on METH-induced relapse and behavioral sensitization in male mice. RNA sequencing and bioinformatics analysis was employed to identify differential expressed (DE) circRNAs, miRNAs, and mRNAs in the nucleus accumbens (NAc) of mice, and the interaction among them was predicted using competing endogenous RNAs (ceRNAs) network analysis. RESULTS: Chronic administration of CBD (40 mg/kg) during the METH withdrawal phase alleviated METH (2 mg/kg)-induced CPP reinstatement and behavioral sensitization in mice, as well as mood and cognitive impairments following behavioral sensitization. Furthermore, 42 DEcircRNAs, 11 DEmiRNAs, and 40 DEmRNAs were identified in the NAc of mice. The circMeis2-miR-183-5p-Kcnj5 network in the NAc of mice is involved in the effects of CBD on METH-induced CPP reinstatement and behavioral sensitization. CONCLUSIONS: This study constructed the ceRNAs network for the first time, revealing the potential mechanism of CBD in treating METH-induced CPP reinstatement and behavioral sensitization, thus advancing the application of CBD in METH use disorders.

Microarray analysis of microrna expression in peripheral blood mononuclear cells of patients with polymyositis and dermatomyositis.

Background and Objectives: MicroRNAs (miRNAs) represent a new class of biomarkers in the context of connective tissue disorders. The miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with polymyositis (PM) and dermatomyositis (DM) have not been fully elucidated. The objective is to investigate miRNAs expression profile in PBMCs of patients with PM/DM. Methods: Microarray technology was used to identify differentially expressed miRNAs in PBMCs obtained from 6 untreated PM/DM patients and 3 healthy controls (HCs). TaqMan-based stem-loop real-time PCR detection was used for validation in a cohort of 34 PM/DM patients and 20 HCs. Results: Microarray analysis revealed 38 differentially expressed miRNAs (24 up-regulated and 14 down-regulated) in PM/DM patients compared to HCs. Four miRNAs (miR-320a, miR-335-3p, miR-34a-5p and miR-454-3p) were chosen for real-time PCR validation. The expression of miR-34a-5p was significantly upregulated in PM/DM group (P < 0.05). In subgroup analysis, miR-34a-5p was significantly upregulated in interstitial lung disease (ILD) group and DM group (P < 0.001). The level of SIRT1, a validated target of miR-34a, was significantly lower in PBMCs of PM/DM patients compared with HCs. Conclusions: MiR-34a-5p may potentially participate in the pathogenesis of PM/DM through SIRT1, and may serve as a potential new biomarker for PM/DM-ILD.

Higher Dietary Inflammatory Index and Increased Mortality Rate of Adults With Hyperuricemia: Findings From the National Health and Nutritional Examination Survey (2001-2018).

OBJECTIVE: This study aimed to assess the association between Dietary Inflammatory Index (DII) score and death among adults with hyperuricemia. METHODS: We collected data from the 2001 to 2018 cohorts of the National Health and Nutritional Examination Survey. Death information was obtained based on death certificate records from the National Death Index through December 31, 2019. The associations between DII score and all-cause, cardiovascular disease (CVD), and cancer death were investigated by using Cox proportional hazards regression models. RESULTS: We enrolled 7,786 participants with hyperuricemia in this study. The DII score ranged from -4.42 to 4.61. Higher DII score was significantly associated with higher levels of body mass index, glycohemoglobin, glucose, low-density lipoprotein-cholesterol, and C-reactive protein (all P < 0.05). During 67,851 person-years of follow-up, deaths of 1,456 participants were identified, including 532 CVD deaths and 246 cancer deaths. After adjusting for potential variables, significant higher risk of all-cause (hazard ratio [HR] 1.18, 95% confidence interval [95% CI] 1.03-1.36, P = 0.01) and CVD (HR 1.30, 95% CI 1.03-1.63, P = 0.02) death was observed for individuals with higher DII scores. Considering the DII score as a continuous variable, the risk of all-cause and CVD death increases 5% (HR 1.05, 95% CI 1.01-1.08) and 8% (HR 1.08, 95% CI 1.02-1.15) with each one-unit increment in DII score, respectively. Subgroup analysis indicated that the association between DII score and all-cause death among participants with hyperuricemia was more significant in males. CONCLUSION: DII score is found to be positively associated with all-cause and CVD death of adults with hyperuricemia. Controlling the intake of proinflammatory food might be a potential strategy to reduce the mortality rate.

Isthmin-1 alleviates cardiac ischemia/reperfusion injury through cGMP-PKG signaling pathway.

AIMS: Ischemia/reperfusion (I/R) injury is an important complication of reperfusion therapy for acute myocardial infarction, extremely compromising the cardiac benefits of revascularization, however, specific and efficient treatment for cardiac I/R injury is still lacking. Isthmin-1 (ISM1) is a novel adipokine, and plays indispensable roles in regulating glycolipid metabolism and cell survival. The present study aims to investigate the potential role and molecular mechanism of ISM1 in cardiac I/R injury using gain- and loss-of-function approaches. METHODS AND RESULTS: Cardiac-specific ISM1 overexpression and silence were achieved using an adeno-associated virus serotype 9 system, and then these mice were subjected to I/R surgery, followed by biochemical test, echocardiography and histopathologic examinations, etc. Meanwhile, neonatal rat cardiomyocytes (NRCMs) with ISM1 silence or overexpression also received simulated I/R (sI/R) injury to further verify its role in vitro. The potential downstream pathways and molecular targets of ISM1 were screened by RNA-sequencing. We also treated injured mice and NRCMs with recombinant ISM1 (rISM1) to explore whether supplementation with ISM1 was sufficient to protect against I/R injury. Furthermore, acute myocardial infarction patients with percutaneous coronary intervention (PCI) and paired healthy controls were included to reveal the clinical relevance of circulating ISM1. Cardiac-specific ISM1 silencing aggravated while ISM1 overexpression alleviated I/R-induced acute cardiac injury and cardiac remodeling and dysfunction. Mechanistically, ISM1 targeted αvß5 integrin to facilitate the nuclear accumulation of nuclear transcription factor Y subunit alpha, transcriptionally increased soluble guanylyl cyclase beta subunit expression, and eventually enhanced cGMP generation. Besides, we confirmed that treatment with rISM1 before or after reperfusion could confer cardioprotective effects in mice. Clinically, lower ISM1 levels post-PCI was associated with worse outcome in patients. CONCLUSION: ISM1 can protect against cardiac I/R injury through cGMP-PKG signaling pathway, and it is a promising therapeutic and predictive target of cardiac I/R injury.

Serum IL-6 level trajectory for predicting the effectiveness and safety of tocilizumab in the treatment of refractory Takayasu arteritis.

AIM: To explore the value of serial monitoring of serum interleukin-6 (IL-6) levels for predicting treatment response and occurrence of adverse events during tocilizumab (TCZ) treatment in refractory Takayasu arteritis (TAK). METHODS: TAK patients receiving TCZ treatment were prospectively recruited and followed up at 1 month, 3 months and then every 3-6 months. Serum IL-6 levels were measured at each visit. Overall response was the combination of complete and partial response, requiring resolution of signs and symptoms, hsCRP and ESR level decreased at least by half, no progression on imaging and dose of glucocorticoid <15 mg/d. RESULTS: Thirty-five patients with a median follow up duration of 17 [9-44] months were included. The change of IL-6 after TCZ treatment for 6 months compared to the baseline was significantly lower in patients achieved overall response at 6, 12, 18 and 24 months. The ratio of IL-6 at 6 months to baseline could predict overall response at 12 and 24 months after TCZ treatment. With a cutoff value of 1.6, the sensitivity and specificity were 83.3 % and 87.5 % for 12 months, while 100 % and 88.9 % for 24 months. Patients with the ratio less than 1.6 were also 9 times more likely to achieve sustained improvement without treatment intensification. No correlation between IL-6 dynamics and occurrence of adverse events was found. CONCLUSIONS: The change of IL-6 levels after TCZ treatment for 6 months compared to the baseline can predict the overall treatment response at 12 months, 24 months and sustained improvement.

Chinese guideline for the diagnosis and treatment of Takayasu's arteritis (2023).

Takayasu's arteritis (TAK) is a chronic granulomatous inflammatory disease that involves aorta and its primary branches. It is characterized by wall thickening, stenosis/obliteration or aneurysm formation of the involved arteries. In order to standardize the diagnosis and treatment of TAK in China, a clinical practice guideline with an evidence-based approach is developed under the leadership of National Clinical Medical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID). Eleven recommendations for 11 clinical questions that are important to the diagnosis and treatment of TAK are developed based on the latest evidence and expert opinions combined with real clinical practice in China.

Serum proteome analysis identifies a potential biomarker for axial psoriatic arthritis.

BACKGROUND: To identify potential serum biomarkers for differentiating between axial psoriatic arthritis (axPsA) and peripheral psoriatic arthritis (pPsA). METHODS: Serum samples were collected from patients with PsA to create a biomarker discovery cohort and a verification cohort. Patients with PsA were classified into axial or peripheral subtypes based on imaging criteria. Untargeted proteomics technology was used in the discovery phase to screen for biomarkers, and candidate biomarkers were evaluated using enzyme-linked immunosorbent assay (ELISA) in the verification phase. RESULTS: We identified 45 significantly differentially expressed proteins (DEPs) between axPsA (n = 20) and pPsA (n = 20) with liquid chromatography-mass spectrometry. Among these DEPs, serum pigment epithelium-derived factor (PEDF) was identified as a candidate biomarker using the Boruta algorithm and lasso regression. Results of ELISA further confirmed that the level of serum PEDF expression was significantly higher in axPsA (n = 37) than in pPsA (n = 51) at the verification cohort (37.9 ± 10.1 vs. 30.5 ± 8.9 µg/mL, p < 0.001). Receiver operating characteristics analysis showed that PEDF had an area under the curve (AUC) of 0.72. Serum PEDF was positively correlated with body mass index and C-reactive protein. Additionally, there was a tendency towards a positive correlation between PEDF and the Bath Ankylosing Spondylitis Disease Activity Index. CONCLUSIONS: This study provided a comprehensive characterization of the proteome in axPsA and pPsA and identified a candidate biomarker, PEDF, that may contribute to early diagnosis for axPsA.

Efficacy and safety of mesenchymal stem cell-derived microvesicles in mouse inflammatory arthritis.

OBJECTIVE: To determine the effective and safe intravenous doses of mesenchymal stem cells (MSCs)-derived microvesicles (MVs) and to elucidate the possible causes of death in mice receiving high-dose MVs. METHODS: MVs were isolated from human MSCs by gradient centrifugation. Mice with collagen-induced arthritis were treated with different doses of intravenous MVs or MSCs. Arthritis severity, white blood cell count, and serum C-reactive protein levels were measured. To assess the safety profile of MSCs and MVs, mice were treated with different doses of MSCs and MVs, and LD50 was calculated. Mouse lungs and heart were assessed by live fluorescence imaging, histopathological measurements, and immunohistochemistry to explore the possible causes of death. Serum concentrations of cTnT, cTnI, and CK-MB were determined by ELISA. With the H9C2 cardiomyocyte cell line,  cellular uptake of MVs was observed using confocal microscopy and cell toxicity was assessed by CCK-8 and flow cytometry. RESULTS: Intravenous treatment with MSCs and MVs alleviated inflammatory arthritis, while high doses of MSCs and MVs were lethal. Mice receiving a maximum dose of MSCs (0.1 mL of MSCs at 109/mL) died immediately, while mice receiving a maximum dose of MVs (0.1 mL of MVs at 1012/mL) exhibited tears, drooling, tachycardia, shortness of breath, unbalanced rollover, bouncing, circular crawling, mania, and death. Some mice died after exhibiting convulsions and other symptoms. All mice died shortly after injecting the maximum dose of MSCs. Histologically, mice receiving high doses of MSCs frequently developed pulmonary embolism, while those receiving high doses of MVs died of myocardial infarction. Consistently, the serum levels of cTnT, cTnI, and CK-MB were significantly increased in the MVs-treated group (P < 0.05). The LD50 of intravenous MVs was 1.60 × 1012/kg. Further, MVs could enter the cell. High doses of MVs induced cell apoptosis, though low concentrations of MVs induced cell proliferation. CONCLUSIONS: Appropriate dosages of MVs and MSCs are effective treatments for inflammatory arthritis while MVs and MSCs overdose is unsafe by causing cardiopulmonary complications.