Deficiency of inflammation-sensing protein neuropilin-2 in myeloid-derived macrophages exacerbates colitis via NF-κB activation.

Neuropilin-2 (NRP2) is a multifunctional protein engaged in the regulation of angiogenesis, lymphangiogenesis, axon guidance, and tumor metastasis, but its function in colitis remains unclear. Here, we found that NRP2 was an inflammation-sensing protein rapidly and dramatically induced in myeloid cells, especially in macrophages, under inflammatory contexts. NRP2 deficiency in myeloid cells exacerbated dextran sulfate sodium salt-induced experimental colitis by promoting polarization of M1 macrophages and colon injury. Mechanistically, NRP2 could be induced via NF-κB activation by TNF-α in macrophages, but exerted an inhibitory effect on NF-κB signaling, forming a negative feedback loop with NF-κB to sense and alleviate inflammation. Deletion of NRP2 in macrophages broke this negative feedback circuit, leading to NF-κB overactivation, inflammatory exacerbation, and more severe colitis. Collectively, these findings reveal inflammation restriction as a role for NRP2 in macrophages under inflammation contexts and suggest that NRP2 in macrophages may relieve inflammation in inflammatory bowel disease. © 2023 The Pathological Society of Great Britain and Ireland.

Comprehensive transcriptomic analysis and machine learning reveal unique gene expression profiles in patients with immune-mediated necrotizing myopathy.

BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy characterized by severe proximal weakness and muscle fiber necrosis, yet its pathogenesis remains unclear. So far, there are few bioinformatics studies on underlying pathogenic genes and infiltrating immune cell profiles of IMNM. Therefore, we aimed to characterize differentially expressed genes (DEGs) and infiltrating cells in IMNM muscle biopsy specimens, which may be useful for elucidating the pathogenesis of IMNM. METHODS: Three datasets (GSE39454, GSE48280 and GSE128470) of gene expression profiling related to IMNM were obtained from the Gene Expression Omnibus database. Data were normalized, and DEG analysis was performed using the limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed using clusterProfiler. The CIBERSORT algorithm was performed to identify infiltrating cells. Machine learning algorithm and gene set enrichment analysis (GSEA) were performed to find distinctive gene signatures and the underlying signaling pathways of IMNM. RESULTS: DEG analysis identified upregulated and downregulated in IMNM muscle compared to the gene expression levels of other groups. GO and KEGG analysis showed that the pathogenesis of IMNM was notable for the under-representation of pathways that were important in dermatomyositis and inclusion body myositis. Three immune cells (M2 macrophages, resting dendritic cells and resting natural killer cells) with differential infiltration and five key genes (NDUFAF7, POLR2J, CD99, ARF5 and SKAP2) in patients with IMNM were identified through the CIBERSORT and machine learning algorithm. The GSEA results revealed that the key genes were remarkably enriched in diverse immunological and muscle metabolism-related pathways. CONCLUSIONS: We comprehensively explored immunological landscape of IMNM, which is indicative for the research of IMNM pathogenesis.

The diagnostic value of sST2 for myocardial fibrosis in idiopathic inflammatory myopathies in subclinical stage of cardiac involvement.

OBJECTIVE: Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. METHODS: A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. RESULTS: IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s.d. 30.4)] vs 14.4 (5.5), P < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P = 0.000), ECV (r = 0.371, P = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P < 0.01), respectively. CONCLUSION: sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM.

Macrophage-derived mir-100-5p orchestrates synovial proliferation and inflammation in rheumatoid arthritis through mTOR signaling.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation, causing substantial disability and reducing life quality. While macrophages are widely appreciated as a master regulator in the inflammatory response of RA, the precise mechanisms underlying the regulation of proliferation and inflammation in RA-derived fibroblast-like synoviocytes (RA-FLS) remain elusive. Here, we provide extensive evidence to demonstrate that macrophage contributes to RA microenvironment remodeling by extracellular vesicles (sEVs) and downstream miR-100-5p/ mammalian target of rapamycin (mTOR) axis. RESULTS: We showed that bone marrow derived macrophage (BMDM) derived-sEVs (BMDM-sEVs) from collagen-induced arthritis (CIA) mice (cBMDM-sEVs) exhibited a notable increase in abundance compared with BMDM-sEVs from normal mice (nBMDM-sEVs). cBMDM-sEVs induced significant RA-FLS proliferation and potent inflammatory responses. Mechanistically, decreased levels of miR-100-5p were detected in cBMDM-sEVs compared with nBMDM-sEVs. miR-100-5p overexpression ameliorated RA-FLS proliferation and inflammation by targeting the mTOR pathway. Partial attenuation of the inflammatory effects induced by cBMDM-sEVs on RA-FLS was achieved through the introduction of an overexpression of miR-100-5p. CONCLUSIONS: Our work reveals the critical role of macrophages in exacerbating RA by facilitating the transfer of miR-100-5p-deficient sEVs to RA-FLS, and sheds light on novel disease mechanisms and provides potential therapeutic targets for RA interventions.

The diagnostic value of urinary N-terminal fragment of titin for skeletal muscle damage in idiopathic inflammatory myopathy.

OBJECTIVES: N-terminal fragment of titin (N-titin) is a marker of sarcomere damage in striated muscles; however, its value in patients with IIM (idiopathic inflammatory myopathy) is unclear. This study aimed to investigate the diagnostic value of N-titin for skeletal muscle damage in patients with IIM. METHODS: Urine samples from 62 patients with IIM, 59 patients with other CTD diseases, and 29 healthy controls were collected to detect N-titin by ELISA assays. Clinical features and laboratory data were all included in logistic regression analysis to obtain the independent predictive factor for skeletal muscle damage. RESULTS: Urinary N-titin level of the IIM group [168.3 (19.0, 1279.0) pmol/mg cr] was significantly higher than that in CTD controls [2.80 (1.53, 3.60)] and healthy controls [1.83 (1.09, 2.95)] (P < 0.001). IIM patients with skeletal muscle injury had a significantly higher level of urinary N-titin [1001.0, (181.8, 1977.0)] than those without [9.3, (5.8, 23.9)] (P < 0.001). The N-titin level was strongly correlated with CK (r = 0.907, P < 0.001) and muscle disease activity assessment scores by Spearman correlation analysis. After adjusting for the anti-MDA5 antibody and cardiac troponin T, N-titin was shown to independently predict skeletal muscle damage in patients with IIM (odds ratio = 1.035, 95% CI: 1.002, 1.069, P = 0.039). The cut-off value of urinary N-titin to diagnose skeletal muscle damage was 89.9 pmol/mg Cr, with a sensitivity of 87.8% and a specificity of 100% (AUC = 0.971, 95% CI: 0.938, 1.000, P < 0.001). CONCLUSION: Urinary N-titin is a non-invasive and independent predictive factor for determining skeletal muscle damage in patients with IIM.

Targeting glycolytic pathway in fibroblast-like synoviocytes for rheumatoid arthritis therapy: challenges and opportunities.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by hyperplastic synovium, pannus formation, immune cell infiltration, and potential articular cartilage damage. Notably, fibroblast-like synoviocytes (FLS), especially rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), exhibit specific overexpression of glycolytic enzymes, resulting in heightened glycolysis. This elevated glycolysis serves to generate ATP and plays a pivotal role in immune regulation, angiogenesis, and adaptation to hypoxia. Key glycolytic enzymes, such as hexokinase 2 (HK2), phosphofructose-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), and pyruvate kinase M2 (PKM2), significantly contribute to the pathogenic behavior of RAFLS. This increased glycolysis activity is regulated by various signaling pathways. MATERIALS AND METHODS: A comprehensive literature search was conducted to retrieve relevant studies published from January 1, 2010, to the present, focusing on RAFLS glycolysis, RA pathogenesis, glycolytic regulation pathways, and small-molecule drugs targeting glycolysis. CONCLUSION: This review provides a thorough exploration of the pathological and physiological characteristics of three crucial glycolytic enzymes in RA. It delves into their putative regulatory mechanisms, shedding light on their significance in RAFLS. Furthermore, the review offers an up-to-date overview of emerging small-molecule candidate drugs designed to target these glycolytic enzymes and the upstream signaling pathways that regulate them. By enhancing our understanding of the pathogenic mechanisms of RA and highlighting the pivotal role of glycolytic enzymes, this study contributes to the development of innovative anti-rheumatic therapies.

Monitoring small airway dysfunction in connective tissue disease-related interstitial lung disease: a retrospective and prospective study.

BACKGROUND: Small airway dysfunction (SAD), a hallmark of early lung function abnormality, is a major component of several chronic respiratory disorders. The role of SAD in patients with connective tissue disease-related interstitial lung disease (CTD-ILD) has not been explored. METHODS: We conducted a two-parts (retrospective and prospective) study to collect pulmonary function tests from CTD-ILD patients. SAD was defined as at least two of the three measures (MMEF, FEF 50%, and FEF 75%) must be 65% of predicted values. Spearman correlation coefficient was used to evaluate association between SAD and other pulmonary function parameters. Mixed effects regression modeling analysis was used to assess response to treatment. RESULTS: CTD-ILD patients with SAD and without SAD were compared in this study. In the retrospective study, pulmonary function tests (PFTs) from 491 CTD-ILD patients were evaluated, SAD were identified in 233 (47.5%). CTD-ILD patients with SAD were less smokers (17.6% vs. 27.9%, p = 0.007) and more females (74.3% vs. 64.0%, p = 0.015) than those without SAD. CTD-ILD patients with SAD had lower vital capacity (% predicted FVC, 70.4 ± 18.3 vs. 80.0 ± 20.9, p < 0.001) and lower diffusion capacity (% predicted DLCO, 58.8 ± 19.7 vs. 63.8 ± 22.1, p = 0.011) than those without SAD. Among 87 CTD-ILD patients prospectively enrolled, significant improvement in % predicted FVC was observed at 12-months follow-up (6.37 ± 1.53, p < 0.001 in patients with SAD; 5.13 ± 1.53, p = 0.002 in patients without SAD), but not in diffusion capacity and SAD parameters. CONCLUSION: In our cohort, about half of CTD-ILD patients have SAD, which is less frequent in smokers and more common in female patients. CTD-ILD patients with SAD have worse pulmonary function compared to those without SAD. Improvement of FVC but no improvement of SAD was observed in CTD-ILD patients after treatment.

Calciphylaxis and its co-occurrence with connective tissue diseases.

Calciphylaxis, also known as calcific uremic arteriopathy, is a rare calcification syndrome that presents as ischemic skin necrosis and severe pain. It has a high mortality rate and is characterised by calcification of the small and medium arteries and micro-thrombosis. Calciphylaxis mainly occurs in patients with end-stage renal disease. In recent years, there have been an increasing number of cases of calciphylaxis associated with connective tissue diseases. Given the absence of clear diagnostic criteria for calciphylaxis thus far, an early diagnosis is crucial for designing an effective multidisciplinary treatment plan. In this article, we review the research progress on calciphylaxis and describe its characteristics in the context of connective tissue diseases.

[YKL-40 Promotes the Expression of Inflammatory Factors in Type â ¡ Alveolar Epithelial Cell Model of A549 Cell Line].

Objective: YKL-40, also known as chitinase-3-like-1 (CHI3L1), is a human cartilage glycoprotein-39, with its N-terminus consisting of tyrosine (Y), lysine (K), and leucine (L), hence the name YKL-40. In this study, we explored whether YKL-40 could promote the expression of inflammatory factors in type Ⅱ alveolar epithelial cells. Methods: A549 cells were cultured in vitro with interleukin (IL)-1ß (20 ng/mL), IL-6 (20 ng/mL), tumor necrosis factor-alpha (TNF-α) (20 ng/mL), and interferon-gamma (IFN-γ) (20 ng/mL). The expression of YKL-40 transcription was determined by RT-qPCR. A549 cells were cultured with IL-1ß at 5, 10, and 20 ng/mL and the expression of YKL-40 protein was determined by Western blot. A549 cells were cultured with recombinant YKL-40 protein at 0, 100, 500, and 1 000 ng/mL and the expression levels of IL-6 and IL-8 were measured by RT-qPCR. Three pairs of small interfering RNAs targeting YKL-40 (si- YKL-40-1/2/3) and the negative control (NC) were designed and used to transfect A549 cells, respectively, and the expression of YKL-40 was determined by RT-qPCR and Western blot. si- YKL-40-3 was screened out for subsequent experiments. In A549 cells, si- YKL-40-3 and si-NC were transfected and, then, IL-1ß (20 ng/mL) was added in for culturing. The expression of YKL-40, IL-6, and IL-8 was determined by RT-qPCR and the expression of multiple factors in the supernatant was measured with the QAH-INF-1 kit. Results: RT-qPCR results showed that IL-1ß could up-regulate YKL-40 protein transcription level compared with that of the control group and the difference was statistically significant ( P<0.01), but IL-6, TNF-α, and IFN-γ could not up-regulate YKL-40 protein transcription level. Western blot results showed that IL-1ß (20 ng/mL) could significantly promote the expression of YKL-40 and, compared with that of the control group, the differences showed by groups treated with different concentrations of IL-1ß were all statistical significant ( P<0.01). After adding human recombinant YKL-40 protein to A549 cells, the results showed that the expression of inflammatory factors IL-6 and IL-8 was significantly increased and the difference was statistically significant compared with that of the control group ( P<0.05). After the expression of YKL-40 was decreased by si- YKL-40-3 transfection, the expression of IL-6 ( P<0.05), IL-8 ( P<0.05), and other inflammatory factors was inhibited compared with that of the control group. Conclusion: YKL-40 can promote the expression and secretion of IL-6, IL-8, and other acute inflammatory factors in A549 cell line, a type Ⅱ alveolar epithelial cell model, thus aggravating the inflammatory response. Targeted inhibition of YKL-40 expression may effectively inhibit inflammatory response.

Association of anti-TNF-α treatment with gut microbiota of patients with ankylosing spondylitis.

OBJECTIVE: Gut dysbiosis contributes to multiple autoimmune diseases, including ankylosing spondylitis, which is commonly treated with tumor necrosis factor (TNF)-α inhibitors (TNFis). Because host TNF-α levels are considered to interact with gut microbiota, we aimed to systematically investigate the microbiota profile of ankylosing spondylitis patients with anti-TNF-α-based treatment and identify potential key bacteria. METHODS: Fecal samples were collected from 11 healthy controls and 24 ankylosing spondylitis patients before/after anti-TNF-α treatment, the microbiota profiles of which were evaluated by 16S ribosomal DNA amplicon sequencing and subsequent bioinformatic analysis. RESULTS: Significantly different microbial compositions were observed in samples from ankylosing spondylitis patients compared with healthy controls, characterized by a lower abundance of short-chain fatty acid (SCFA)-producing bacteria. All patients exhibited a positive response after anti-TNF-α treatment, accompanied by a trend of restoration in the microbiota compositions and functional profile of ankylosing spondylitis patients to healthy controls. In particular, the abundance of SCFA-producing bacteria (e.g. Megamonsa and Lachnoclostridium ) was not only significantly lower in ankylosing spondylitis patients than in healthy controls and restored after anti-TNF-α treatment but also negatively correlated with disease severity (e.g. cor = -0.52, P = 8 × 10 -5 for Megamonsa ). In contrast, Bacilli and Haemophilus may contribute to ankylosing spondylitis onset and severity. CONCLUSIONS: Microbiota dysbiosis in ankylosing spondylitis patients can be restored after anti-TNF-α treatment, possibly by impacting SCFA-producing bacteria.

Quantitative evaluation of disease severity in connective tissue disease-associated interstitial lung disease by dual-energy computed tomography.

BACKGROUND: High-resolution computed tomography (HRCT) is recommended diagnosing and monitoring connective tissue disease-associated interstitial lung disease (CTD-ILD). Quantitative computed tomography has the potential to precisely assess the radiological severity of CTD-ILD, but has still been under study. OBJECTIVE: To investigate whether dual-energy computed tomography (DECT), a novel quantitative technique, can be used for quantitative severity assessment in CTD-ILD. METHODS: This cross sectional study recruited adult CTD-ILD patients who underwent DECT scans from the ICE study between October 2019 and November 2021. DECT parameters, including effective atomic number (Zeff), lung (lobe) volume, and monochromatic CT number (MCTN) of each lung lobe, were evaluated. CTD-ILD was classified into extensive CTD-ILD and limited CTD-ILD by staging algorithm using combined forced vital capacity (FVC)%predicted and total extent of ILD (TEI) on CT. Dyspnea, cough, and life quality were scored by Borg dyspnea score, Leicester cough questionnaire (LCQ), and short-form 36 health survey questionnaire (SF-36), respectively. RESULTS: There was a total of 147 patients with DECT scans enrolled. Higher Zeff value (3.104 vs 2.256, p < 0.001), higher MCTN (- 722.87 HU vs - 802.20 HU, p < 0.001), and lower lung volume (2309.51cm3 vs 3475.21cm3, p < 0.001) were found in extensive CTD-ILD compared with limited CTD-ILD. DECT parameters had significant moderate correlations with FVC%predicted (|r|= 0.542-0.667, p < 0.01), DLCO%predicted (|r|= 0.371-0.427, p < 0.01), and TEI (|r|= 0.485-0.742, p < 0.01). Receiver operating characteristic (ROC) analysis indicated MCTN averaged over the whole lung had the best performance for extensive CTD-ILD discrimination (AUC = 0.901, cut-off: - 762.30 HU, p < 0.001), with a sensitivity of 82.1% and a specificity of 85.4%. The Zeff value was the independent risk factor for dyspnea (OR = 3.644, 95% CI: 1.846-7.192, p < 0.001) and cough (OR = 3.101, 95% CI: 1.528-6.294, p = 0.002), and lung volume significantly contributed to the mental component summary (MCS) in SF-36 (standardized ß = 0.198, p < 0.05). CONCLUSIONS: DECT can be applied to evaluate the severity of CTD-ILD.

Neutrophil-to-lymphocyte ratio is a predictive marker for anti-MDA5 positive dermatomyositis.

BACKGROUND: NLR is a systemic inflammatory marker that have been associated with overall survival in patients with some rapidly progressive disease. There are few data about the diagnostic and predictive value of NLR in autoimmune diseases, and it has not been described in anti-MDA5 positive DM. We try to correlate neutrophil-to-lymphocyte ratio (NLR) with fatality from dermatomyositis in anti-MDA5 positive patients. METHOD: A retrospective study in which 195 patients were enrolled was conducted. Clinical and laboratory information was collated and ratios of neutrophil to lymphocyte counts (NLR) calculated. The primary end point was all-cause death. RESULT: Of the 195 patients studied, all had interstitial lung disease, including 140 survivors and 55 non-survivors. An optimal NLR cut-off value of 4.86 for mortality prediction was identified. The NLR of non-survivors was significantly higher than that of survivors (p < 0.001). Plasma levels of lactate dehydrogenase (LDH) and C-reactive protein were significantly increased when NLR was greater than 4.86. Results of multivariate analysis established that NLR > 4.86 was an independent predictor of mortality (HR: 2.52; 95%CI: 1.33-4.78; p = 0.005). Abstinence from smoking (HR: 2.66; 95%CI: 1.33-4.78; p = 0.003), emergence of rapidly progressive interstitial lung disease (RPILD; HR: 4.38; 95%CI: 2.37-8.08; p < 0.001), low plasma LDH (HR: 3.82; 95%CI: 2.06-7.11; p < 0.001) and presentation with dyspnea (HR: 2.17; 95%CI: 1.22-3.86; p = 0.009) were all protective factors predictive of survival. CONCLUSION: NLR is a cost-effective and widely accessible biomarker with utility for risk stratification in patients with anti-MDA5 + dermatomyositis.

Clinical value of YKL-40 in patients with polymyositis/dermatomyositis: A cross-sectional study and a systematic review.

INTRODUCTION: We performed a cross-sectional study to investigate the clinical usefulness of YKL-40 in patients with dermatomyositis (DM) and conducted a systematic review to summarize the clinical value of YKL-40 in patients with polymyositis (PM)/DM. MATERIALS AND METHODS: A cross-sectional study and a systematic review were performed to study the clinical value of YKL-40 in patients with PM/DM. Serum YKL-40 level was detected using enzyme-linked immunosorbent assay, and its association with clinical and laboratory parameters was analyzed. In the systematic review, electronic databases of OVID Embase, OVID Medline, and web of science were searched to collect studies that reported clinical use of YKL-40 in patients with PM/DM. RESULTS: In the cross-sectional study, serum YKL-40 level was higher in patients with DM than in healthy controls (median [interquartile range]: 84.09 [52.72-176.4] ng/ml versus 27.37 [12.30-53.58] ng/ml, p < 0.0001). Serum levels of YKL-40 were associated with the course of DM (r = -0.469, p < 0.001), CRP (r = 0.303, p = 0.043), CK (r = 0.263, p = 0.037), and global disease activity (r = 0.628, p < 0.001). The area under the ROC curve was 0.835 (95% confidence interval 0.751-0.920). In the systematic review, a total of four studies were included with moderate to high quality. Serum level of YKL-40 has the possibility for diagnosing PM/DM, identifying PM/DM patients with interstitial lung disease (ILD) or rapid progress ILD, and predicting death. CONCLUSION: Serum YKL-40 level is a possible useful biomarker for PM/DM diagnosis and may be used to predict prognosis.

Phenotyping of myocardial involvement by cardiac magnetic resonance in idiopathic inflammatory myopathies.

OBJECTIVES: Cardiac dysfunction is commonly noted in patients with idiopathic inflammatory myopathies (IIMs). This study aimed to investigate the characteristics of cardiac dysfunction using cardiac magnetic resonance (CMR) in polymyositis (PM), dermatomyositis (DM) and necrotising myositis (NM). METHODS: Fifty-one patients with IIMs and 20 matched healthy controls (HCs) were assessed using CMR examination. The clinical data, cardiac serum markers and autoimmune antibodies were determined for all patients. Cardiac involvement was identified by myocardial native T1, extracellular volume (ECV), late gadolinium enhancement (LGE) and left ventricular ejection fraction (LVEF). RESULTS: Different subtypes of IIMs showed different patterns of LGE and varying degrees of myocardial damage. The PM subgroup showed higher native T1 (p = 0.010) and ECV (p = 0.000) than the HCs. The prevalence of LGE was comparable between the PM and DM subgroups (40.0% vs. 31.6%, p = 0.741); however, it was higher in the PM subgroup than in the NM subgroup (40% vs. 0.0%, p = 0.014). Patients with positive LGE in the PM subgroup showed a higher proportion of positive LGE (p = 0.018) and lower LVEF (p = 0.024) than those with positive LGE in the DM subgroup. In multivariate analysis, the presence of LGE could be predicted by increased NT-proBNP (p = 0.036, OR = 1.001) and anti-MDA-5 antibody positivity (p = 0.011, OR = 12.4). The risk factors associated with native T1 were NT-proBNP (p = 0.016, ß = 0.353) and body mass index (BMI) (p = 0.024, ß = - 0.331). CONCLUSIONS: Distinct cardiac involvements in different subtypes of IIMs were identified using CMR. Elevated NT-proBNP and a low BMI were the risk factors associated with LGE and elevated native T1. KEY POINTS: • The characteristics of cardiac involvement in different subtypes of IIMs could be identified with cardiac magnetic resonance. • The NT-proBNP levels could reflect focal and diffuse myocardial damage in patients with IIMs.

Multiparametric cardiovascular magnetic resonance characteristics and dynamic changes in myocardial and skeletal muscles in idiopathic inflammatory cardiomyopathy.

BACKGROUND: Idiopathic inflammatory myopathy (IIM) manifest as systematic muscle involvement. Multiparametric cardiovascular magnetic resonance (CMR) could be a useful technique to detect systemic involvement and disease progression in IIM patients. This study aimed to describe the tissue characteristics and dynamic changes in myocardial and skeletal muscles after treatment in IIM patients. METHODS: Forty-four consecutively recruited IIM patients (49.0 ± 12.0 years; 22 males) underwent 3 T CMR at first diagnosis, and 28 patients underwent follow-up scan after receiving standard treatment for more than 1 year. Thirty age- and sex-matched healthy subjects served as controls. The CMR protocol included: cines, T2-weighted (T2w), late gadolinium enhancement (LGE), T1 and T2 mapping, and extracellular volume (ECV) evaluated for the myocardium, and T1 and T2 mapping and ECV evaluated for skeletal muscles. Correlations between laboratory biomarkers and myocardial and skeletal tissue characteristics were analyzed. Comparisons between baseline and follow-up scans were performed using paired t-tests. RESULTS: At baseline, IIM patients showed significantly decreased hematocrit, higher left ventricular (LV) mass index, right ventricular (RV) volume index, myocardial and skeletal native T1, T2 mapping, and ECV than healthy controls. Significant correlations were found among myocardial native T1, T2 mapping, and ECV values and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels, and significant correlations between skeletal T2 mapping and inflammatory biomarkers in IIM patients. During the follow-up, 28 patients underwent repeated CMR scan (median interval, 14.5 months, interquartile range: 13.2-15.5 months). Significant relief from clinical symptoms and decreased inflammatory biomarkers levels were observed. Significant reduction in myocardial native T1, T2, ECV, and skeletal native T1, T2, and ECV were observed during the follow-up assessment. CONCLUSIONS: Both myocardial and skeletal muscles in newly diagnosed IIM patients show distinct characteristics on multiparametric CMR. In addition, significant changes were observed in patients showing clinical remission after effective treatment, which suggests that quantitative T1, T2, and ECV techniques may have potential clinical value in IIM patients.

[Diagnosis and Treatment of 43 Patients with IgG4-related Disease].

OBJECTIVE: To summarize the clinicopathological characteristics, diagnosis and treatment of IgG4-related disease (IgG4-RD). METHODS: The clinical data of 43 cases with IgG4-RD diagnosed from January 2013 to December 2017 were retrospectively analyzed. The clinical data of the patients including clinical characteristics, accessory examinations, diagnosis, and treatment were collected. RESULTS: Among the 43 patients with IgG4-RD, the ratio of male to female was 3∶1, the mean age was (51.3±15.9) years. Eleven patients had gastrointestinal symptoms, including 5 cases of IgG4-related cholangitis with the feature of dilation of the biliary system and narrowing of the lumen in the abdominal enhanced CT scans, and 6 cases of IgG4-related autoimmune pancreatitis with the feature of pancreatic enlargement or soft tissue density shadow in the abdominal enhanced CT scans. There were 10 cases (23.3%) with periorbital involvement, with the feature of intraorbital soft tissue nodule in the CT scan. Besides, 9 cases (20.9%) had lymphadenopathy, 6 cases (14.0%) had fever. The results of autoimmune antibody tests showed that 14 of 42 patients had increased antinuclear antibody (ANA). Among 40 patients who underwent immunoglobulin tests, 25 cases had elevated IgG, 12 cases had increased IgA, and 29 cases had increased IgE. Coombs test were performed for 6 cases and 4 patients were positive. Serum immunoglobulin G4 subtypes showed that the IgG4 levels of 35 patients were higher than 1 350 mg/L. The immunohistochemistry showed that IgG4 (+) cells (3->500/HPF) were infiltrated, with the CD20 (+), CD3ε (+) or CD138 (+). Among the 43 patients, 5 patients underwent operations due to misdiagnosis. All patients were treated with steroid and immunosuppressive agents after diagnosis, and their clinical symptoms were improved. CONCLUSION: The clinical symptoms of IgG4-RD are various, involving multiple organs. Therefore, the standardized diagnosis and treatment of IgG4-RD should be strengthened.