Predictive modeling of co-infection in lupus nephritis using multiple machine learning algorithms.

This study aimed to analyze peripheral blood lymphocyte subsets in lupus nephritis (LN) patients and use machine learning (ML) methods to establish an effective algorithm for predicting co-infection in LN. This study included 111 non-infected LN patients, 72 infected LN patients, and 206 healthy controls (HCs). Patient information, infection characteristics, medication, and laboratory indexes were recorded. Eight ML methods were compared to establish a model through a training group and verify the results in a test group. We trained the ML models, including Logistic Regression, Decision Tree, K-Nearest Neighbors, Support Vector Machine, Multi-Layer Perceptron, Random Forest, Ada boost, Extreme Gradient Boosting (XGB), and further evaluated potential predictors of infection. Infected LN patients had significantly decreased levels of T, B, helper T, suppressor T, and natural killer cells compared to non-infected LN patients and HCs. The number of regulatory T cells (Tregs) in LN patients was significantly lower than in HCs, with infected patients having the lowest Tregs count. Among the ML algorithms, XGB demonstrated the highest accuracy and precision for predicting LN infections. The innate and adaptive immune systems are disrupted in LN patients, and monitoring lymphocyte subsets can help prevent and treat infections. The XGB algorithm was recommended for predicting co-infection in LN.

Efferocytosis: Current status and future prospects in the treatment of autoimmune diseases.

Billions of apoptotic cells are swiftly removed from the human body daily. This clearance process is regulated by efferocytosis, an active anti-inflammatory process during which phagocytes engulf and remove apoptotic cells. However, impaired clearance of apoptotic cells is associated with the development of various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. In this review, we conducted a comprehensive search of relevant studies published from January 1, 2000, to the present, focusing on efferocytosis, autoimmune disease pathogenesis, regulatory mechanisms governing efferocytosis, and potential treatments targeting this process. Our review highlights the key molecules involved in different stages of efferocytosis-namely, the "find me," "eat me," and "engulf and digest" phases-while elucidating their relevance to autoimmune disease pathology. Furthermore, we explore the therapeutic potential of modulating efferocytosis to restore immune homeostasis and mitigate autoimmune responses. By providing theoretical underpinnings for the targeting of efferocytosis in the treatment of autoimmune diseases, this review contributes to the advancement of therapeutic strategies in this field.

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.

Repurposed drug agomelatine is therapeutic against collagen-induced arthritis via iNOS targeting.

BACKGROUND: The most promising biologics tumor necrosis factor α (TNFα) inhibitors are effective in treating rheumatoid arthritis (RA) in only 50-70 % of the cases; thus, new drugs targeting TNFα-mediated inflammation are required. METHODS: Firstly, the drugs that could inhibit FLS proliferation and TNFα induced inflammatory cytokine production were screened. Secondly, treatment effects of the identified drugs were screened in collagen-induced arthritis (CIA) mouse model. Thirdly, the inhibitory effect of the identified drug, agomelatine (AOM), on TNFα induced inflammatory cytokine production and NF-κB activity were confirmed. Fourthly, bioinformatics was applied to predict the binding target of AOM and the binding was confirmed, and the already known inhibitor of target was used to test the treatment effect for CIA mouse model. Finally, the effect of AOM on signaling pathway was tested and on TNFα induced inflammatory cytokine production was observed after inhibiting the target. RESULTS: AOM effectively inhibited TNFα-induced NF-κB activation, NF-κB p65 translocation, and inflammatory cytokines production in vitro and was therapeutic against CIA. The mechanistic study indicated inducible nitric oxide synthase (iNOS) as the binding target of AOM. 1400 W, a known inhibitor of iNOS, could effectively treat CIA by decreasing iNOS activity and the levels of inflammatory cytokines. The inhibitory effect of AOM on TNFα-induced inflammation was further elucidated by 1400 W, or NF-κB p65 inhibitor JSH-23, indicating that AOM is therapeutic against CIA via iNOS/ERK/p65 signaling pathway after binding with iNOS. CONCLUSIONS: AOM is therapeutic against CIA via inhibition of the iNOS/ERK/p65 signaling pathway after binding with iNOS.

Safety and efficacy of phage application in bacterial decolonisation: a systematic review.

Colonisation by bacterial pathogens typically precedes invasive infection and seeds transmission. Thus, effective decolonisation strategies are urgently needed. The literature reports attempts to use phages for decolonisation. To assess the in-vivo efficacy and safety of phages for bacterial decolonisation, we performed a systematic review by identifying relevant studies to assess the in-vivo efficacy and safety of phages for bacterial decolonisation. We searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and the Cochrane Library to identify relevant articles published between Jan 1, 1990, and May 12, 2023, without language restrictions. We included studies that assessed the efficacy of phage for bacterial decolonisation in humans or vertebrate animal models. This systematic review is registered with PROSPERO, CRD42023457637. We identified 6694 articles, of which 56 (51 animal studies and five clinical reports) met the predetermined selection criteria and were included in the final analysis. The gastrointestinal tract (n=49, 88%) was the most studied bacterial colonisation site, and other sites were central venous catheters, lung, nose, skin, and urinary tract. Of the 56 included studies, the bacterial load at the colonisation site was reported to decrease significantly in 45 (80%) studies, but only five described eradication of the target bacteria. 15 studies reported the safety of phages for decolonisation. No obvious adverse events were reported in both the short-term and long-term observation period. Given the increasing life-threatening risks posed by bacteria that are difficult to treat, phages could be an alternative option for bacterial decolonisation, although further optimisation is required before their application to meet clinical needs.

Augmenting regulatory T cells: new therapeutic strategy for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune condition marked by inflammation of the joints, degradation of the articular cartilage, and bone resorption. Recent studies found the absolute and relative decreases in circulating regulatory T cells (Tregs) in RA patients. Tregs are a unique type of cells exhibiting immunosuppressive functions, known for expressing the Foxp3 gene. They are instrumental in maintaining immunological tolerance and preventing autoimmunity. Increasing the absolute number and/or enhancing the function of Tregs are effective strategies for treating RA. This article reviews the studies on the mechanisms and targeted therapies related to Tregs in RA, with a view to provide better ideas for the treatment of RA.

Hypouricemia as a novel predictor of mortality in anti-MDA5 positive dermatomyositis patients with ILD: A retrospective cohort study.

OBJECTIVE: Anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis (MDA5+ DM) is a unique subtype of idiopathic inflammatory myopathy (IIM) that is associated with rapidly progressive interstitial lung disease (RPILD) and high mortality. This retrospective study aimed to identify predictors of mortality and discover novel easily detectable indicators. METHODS: We retrospectively reviewed 183 MDA5+ DM-ILD patients who were from West China Hospital of Sichuan University myositis cohort, the largest single-center cohort of southwest China, from January 2016 to October 2021. Clinical characteristics were reviewed, and risk factors for mortality were determined by univariate and multivariable Cox regression analyses. RESULTS: Of the 183 MDA5+ DM-ILD patients, 59 were presented with RP-ILD, and 53 died during the follow-up period. Compared with the survived patients, deceased patients had higher rates of dyspnea, higher concentrations of CRP, and LDH, but lower rates of heliotrope sign, lower quantity of lymphocyte and lower levels of serum uric acid (SUA). Notably, patients with hypouricemia (SUA <154 µmol/L) had higher concentrations of CRP and LDH, higher neutrophil counts, lower lymphocyte counts and higher mortality rate when compared with the non-hypouricemia group. Multivariate Cox regression analyses confirmed that hypouricemia, smoking, RPILD, high HRCT score, elevated LDH, and lymphopenia were independent risk factors for mortality in MDA5+ DM-ILD patients. Moreover, patients with hypouricemia had significantly lower survival rates than non-hypouricemia patients. CONCLUSION: Our study identified hypouricemia as a non-redundant promising prognostic factor for the mortality of MDA5+ DM-ILD patients, which may hopefully provide insight into the prevention and pathogenesis study.

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.

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.

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.

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.

Systematic review and meta-analysis of the current literature on tocilizumab in patients with refractory Takayasu arteritis.

Objective: To present the pooled quantitative evidence of baseline characteristics and clinical outcomes of tocilizumab (TCZ) in patients with refractory Takayasu arteritis (TAK). Methods: A comprehensive systematic review and meta-analysis was performed on all available studies retrieved from the MEDLINE, Embase, and Cochrane databases, using TCZ in patients with refractory TAK. We applied the commands metan and metaprop_one in Stata Software to pool overall estimates of continuous data and binomial data, respectively. A random-effects model was recruited for analysis. Results: Nineteen studies with 466 patients were included in this meta-analysis. The mean age at implementation of TCZ was 34.32 years. Female sex and Numano Type V were the most prominent baseline characteristics. During the 12-month follow-up when receiving TCZ treatment, pooled CRP was 1.17 mg/L (95% confidence interval [CI] -0.18-2.52), pooled ESR was 3.54 mm/h (95% CI 0.51-6.58), and pooled glucocorticoid dose was 6.26 mg/d (95% CI 4.24-8.27). Approximately 76% (95% CI 58-87%) of patients achieved a decrease in glucocorticoid dosage. Meanwhile, patients with TAK had a remission rate of 79% (95% CI 69-86%), a relapse rate of 17% (95% CI 5-45%), an imaging progress rate of 16% (95% CI 9-27%), and a retention rate of 68% (95% CI 50-82%). Adverse events occurred in 16% (95% CI 5-39%) of patients, and infection was the most common adverse event, with a rate of 12% (95% CI 5-28%). Conclusion: TCZ treatment can provide favorable outcomes in terms of inflammatory markers, steroid-sparing effects, clinical response, drug retention and minimizing adverse effects for patients with refractory TAK.

Fexofenadine protects against lipopolysaccharide-induced acute lung injury by targeting cytosolic phospholipase A2.

OBJECTIVE: Acute lung injury (ALI) causes acute respiratory distress syndrome, with a high mortality rate of 40%, with currently available pharmacological treatments. Cytosolic phospholipase A2 (cPLA2) plays a critical role in the lipopolysaccharide (LPS)-induced pathology of ALI. This study assessed the therapeutic effects of fexofenadine (FFD), an on-market small-molecule drug that can target cPLA2 in LPS-induced ALI. METHODS: Primary macrophages obtained from the bone marrow of wild-type and cPLA2 knockout mice and the alveolar macrophage cell line, MHS were used to test the inhibitory effect of FFD on the cPLA2/ERK/p65 signaling pathway, NF-κB p65 translocation, and cytokine and chemokine production. An LPS-induced ALI mouse model was used to assess the treatment effects of FFD. Flow cytometry detected subsets of macrophages and neutrophils. cPLA2 activity and downstream hydrolysates were detected. Treatment with a cPLA2 inhibitor or NF-κB p65 inhibitor confirmed that FFD functioned through the cPLA2/ERK/p65 signaling pathway by targeting cPLA2. RESULTS: FFD reduced the infiltration of macrophages and neutrophils, decreased the protein secretion in bronchoalveolar lavage fluid, and reduced the production of TNFα, IL-1ß, IL-6, MCP-1, and IL-8 in the lung, bronchoalveolar lavage fluid, and sera of LPS-induced ALI mice. FFD inhibited cPLA2 activity, suppressed the cPLA2/ERK/p65 signaling pathway, inhibited translocation of p65, and decreased the production of cytokines, chemokines, and downstream hydrolysates of cPLA2, arachidonic acid, and leukotriene B4. CONCLUSION: FFD inhibits the cPLA2/ERK/p65 signaling pathway by targeting cPLA2. Therefore, FFD is promising as a therapeutic against cPLA2-involved diseases, particularly ALI.

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.

Screening value of lung ultrasound in connective tissue disease related interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD) that can lead to poor quality of life and prognosis. OBJECTIVES: To explore the screening value of lung ultrasound (LUS) for connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: Data of patients with CTD were collected, and each patient underwent LUS, high-resolution computed tomography (HRCT), and pulmonary function tests. Considering HRCT is the gold standard for diagnosing CTD-ILD, patients were divided into CTD-ILD and CTD-non-ILD groups. The LUS and HRCT results were assessed using semiquantitative and Warrick scores, respectively. Pulmonary function results were also collected. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of LUS diagnosis. Spearman correlation analysis was used to analyze the correlation between LUS, HRCT, and lung function indices. RESULTS: A total of 88 patients (65 with CTD-ILD and 23 with CTD-non-ILD) were included in this study. The sensitivity and specificity of LUS for the diagnosis of CTD-ILD were 86.60% and 82.60%, respectively, which was consistent with the HRCT results (P < 0.05). The LUS results (total number of B-lines, frequency of B-line, pleural thickness, and pleural-line irregularity) were positively correlated with the HRCT Warrick score (r = 0.77, 0.76, 0.65 and 0.71, P < 0.05). CONCLUSIONS: LUS may be a promising tool for screening patients with CTD-ILD.

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.

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.

Case Report: Brachydactyly Type A1 Induced by a Novel Variant of in-Frame Insertion in the IHH Gene.

Brachydactyly type A1 (BDA1) is an autosomal dominant inherited disease characterized by the shortness/absence of the middle phalanges, which can be induced by mutations in the Indian hedgehog gene (IHH). Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by joint destruction, synovitis, and the presence of autoantibodies. In this study, the proband was diagnosed with both BDA1 and RA. We performed whole-exome sequencing in a four-generation Chinese family to investigate their inherited causal mutation to BDA1. A novel in-frame insertion variant in IHH: NM_002,181.4: c.383_415dup/p.(R128_H138dup) was identified in the BDA1 pedigree. This insertion of 11 amino acids was located in the highly conserved amino-terminal signaling domain of IHH and co-segregated with the disease status. This adds one to the total number of different IHH mutations found to cause BDA1. Moreover, we found a potential causal germline variant in CRY1 for a molecular biomarker of RA (i.e., a high level of anti-cyclic citrullinated peptide). Collectively, we identified novel variants in IHH for inherited BDA1, which highlights the important role of this gene in phalange development.