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ID PMID Title PublicationDate abstract
32844819 Progressive Pseudo-rheumatoid Dysplasia: Two Cases in One Family. 2020 Jul Progressive pseudo-rheumatoid dysplasia is an autosomal recessive skeletal dysplasia. Spine radiographs show platyspondyly. The clinical presentations are similar to juvenile idiopathic arthritis, but not the laboratory findings. We report 2 cases of progressive pseudo-rheumatoid dysplasia in the same family. A 26 years old male was admitted in the department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh with the complain of inflammatory joint pain, joint swelling, range-of-motion limitation, and joint deformities in the hands, wrists, ankles, knees and hips for 20 years. He was treated as juvenile idiopathic arthritis with different anti-inflammatory medications having progressing by flares and remissions. Erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti ccp antibody and HLAB27 levels were normal. Synovial fluid of the knees showed mechanical properties. Plain radiographs of the hands and knees showed evidence of joint destruction. Radiograph of the pelvis notes bilateral hip dysplasia. Platyspondyly was found in spinal radiograph. The diagnosis of juvenile idiopathic arthritis was reconsidered. His 22 years old younger brother had similar manifestations without laboratory evidence of inflammation; radiographs disclosed dysplasia of the hips and metacarpophalangeal epiphyses. Manifestation of spinal stiffness, thoracic kyphosis, and motion-range limitation at the hips; radiographs showed normal sacroiliac joints and bilateral hip dysplasia. So, a diagnosis of progressive pseudo-rheumatoid dysplasia with polyarticular involvement was done.
32922141 Aliskiren, tadalafil, and cinnamaldehyde alleviate joint destruction biomarkers; MMP-3 and 2020 Sep Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, which is accompanied by progressive joint damage and disability. The intolerability of conventional antirheumatic drugs by some patients necessitates the search for effective antirheumatic agents having better tolerability. In the current work, we aimed to investigate the efficacy of cinnamaldehyde, tadalafil, and aliskiren as potential antirheumatic candidates and to explore their modulatory effects on joint destruction, inflammatory response, and intracellular signaling. Arthritis was induced in female Wistar rats by complete Freund's adjuvant (CFA) 0.4 ml s.c. on days 1, 4, and 7. Treated groups received their respective drugs, starting from day 13, daily for 3 weeks. Methotrexate and prednisolone were the standard antirheumatic drugs, while cinnamaldehyde, tadalafil, and aliskiren were the test agents. Treatment with cinnamaldehyde, tadalafil, or aliskiren reduced serum levels of rheumatoid factor, and pro-inflammatory cytokines; tumor necrosis factor-alpha and interleukin-6 (IL-6), along with elevated level of IL-10 which is an anti-inflammatory cytokine. Besides, cartilage and bone destruction biomarkers; matrix metalloproteinase-3 (MMP-3) and receptor activator of nuclear factor-kappa B ligand (RANKL); were significantly reduced after treatment with the test agents, which was further confirmed by histopathological investigation. The elevated protein expressions of phosphorylated-Janus kinase 2 (p-JAK2), phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), and inducible nitric oxide synthase (iNOS) in articular tissue were markedly attenuated after treatment with cinnamaldehyde, tadalafil, or aliskiren, while that of endothelial nitric oxide synthase (eNOS) was greatly enhanced. In addition, oxidative stress and inflammatory markers such as malondialdehyde, nitric oxide, and myeloperoxidase were reduced in joint tissue after treatment with the test agents, while glutathione content was elevated. Furthermore, the renin inhibitor aliskiren produced effects close to those of the normal and methotrexate, the gold standard antirheumatic drug, in most of the measured parameters. Collectively, these findings led to the assumption that the downregulation of IL-6/JAK2/STAT3 signaling by cinnamaldehyde, tadalafil, and aliskiren could alleviate joint destruction by MMP-3 and RANKL, reduce iNOS, and enhance eNOS expressions. Moreover, aliskiren could be a promising therapeutic agent for RA, because of its ability to normalize most of the measured parameters after CFA-induced arthritis.
32270946 Quantitative Assessment of Salivary Gland Parenchymal Vascularization Using Power Doppler 2020 Jun 1 BACKGROUND: Primary Sjögren’s syndrome is a chronic inflammatory autoimmune disease. Minor salivary gland biopsy is the gold standard for the diagnosis of primary Sjögren’s syndrome. Superb microvascular imaging, power Doppler ultrasound, and color Doppler of the salivary glands represent non-invasive, non-irradiating modality for evaluating the vascularity of the salivary glands in the diagnosis and follow-up of primary Sjögren’s syndrome. AIMS: To evaluate the efficacy of superb microvascular imaging and vascularity index in salivary glands for the sonographic diagnosis of primary Sjögren’s syndrome. STUDY DESIGN: Prospective case-control study. METHODS: Twenty participants with primary Sjögren’s syndrome and 20 healthy subjects were included in the study. Both parotid glands and submandibular glands were evaluated by superb microvascular imaging, power Doppler ultrasound, and color Doppler. The diagnostic accuracy of superb microvascular imaging was compared using these techniques. RESULTS: In the patient group, the vascularity index values of superb microvascular imaging in parotid glands and submandibular glands were 3.5±1.66, 5.06±1.94, respectively. While the same values were 1.0±0.98 and 2.44±1.34 in the control group (p≤0.001). In the patient group, the vascularity index values of power Doppler ultrasound in parotid glands and submandibular glands were 1.3±1.20 and 2.59±1.82, respectively. While the same values were 0.3±0.32 and 0.85±0.68 in the control group (p≤0.001). The superb microvascular imaging vascularity index cut-off value for the diagnosis of primary Sjögren’s syndrome in parotid glands that maximizes the accuracy was 1.85 (area under the curve: 0.906; 95% confidence interval: 0.844, 0.968), and its sensitivity and specificity were 87.5% and 72.5%, respectively. While the superb microvascular imaging vascularity index cut-off value for the diagnosis of primary Sjögren’s syndrome in submandibular gland that maximizes the accuracy was 3.35 (area under the curve: 0.873; 95% confidence interval: 0.800, 0.946), its sensitivity and specificity were 82.5% and 70%, respectively. CONCLUSION: Superb microvascular imaging with high reproducibility of the vascularity index has a higher sensitivity and specificity than the power Doppler ultrasound in the diagnosis of primary Sjögren’s syndrome. It can be a noninvasive technique in the diagnosis of primary Sjögren’s syndrome when used with clinical, laboratory and other imaging methods.
31763772 Prevalence, correlates, and impact of sleep disturbance in Chinese patients with primary S 2020 Mar AIM: Sleep disturbances are common in primary Sjögren's syndrome (pSS) patients and may lead to disease aggravation and decreased health-related quality of life (HRQoL). There are currently no known reported studies related to the prevalence, correlates, and impact of sleep disturbance in pSS patients from China. Therefore, this study aims to assess the sleep quality in Chinese pSS patients and evaluate its relationship with the disease activity, quality of life and mood disorders. METHODS: A self-report survey was administered to 221 pSS patients and 198 healthy individuals using the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Disease activity and damage were evaluated with the European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI). Independent samples t tests, Chi-square analysis, logistic regression were used to analyze these data. RESULTS: Our results found that the prevalence of poor sleep (PSQI ≥ 6) was 57.5% and the mean global score of PSQI was 6.57 (SD 3.19) in patients, which were significantly higher than the controls (32.3% and 4.93 [SD 2.86], respectively). When trying to fall asleep, patients with pSS had some sleep disturbances, reduced sleep efficiency, increased number of awakenings than controls. There were significant correlations among dryness, ocular surface disease, HRQoL, pain, disease activity, anxiety/depression and sleep quality in pSS patients. Meanwhile, logistic regression models identified depression and Short Form-36 mental composite score as predictors of poor sleep quality. CONCLUSIONS: Sleep disturbances are commonly reported in pSS patients and sleep quality is lower in pSS patients than in healthy controls. The data suggested the need for holistic assessment and management of pSS patients.
33321888 Identification of Metabolic Biomarkers in Relation to Methotrexate Response in Early Rheum 2020 Dec 10 This study aimed to identify baseline metabolic biomarkers for response to methotrexate (MTX) therapy in rheumatoid arthritis (RA) using an untargeted method. In total, 82 baseline plasma samples (41 insufficient responders and 41 sufficient responders to MTX) were selected from the Treatment in the Rotterdam Early Arthritis Cohort (tREACH, trial number: ISRCTN26791028) based on patients' EULAR response at 3 months. Metabolites were assessed using high-performance liquid chromatography-quadrupole time of flight mass spectrometry. Differences in metabolite concentrations between insufficient and sufficient responders were assessed using partial least square regression discriminant analysis (PLS-DA) and Welch's t-test. The predictive performance of the most significant findings was assessed in a receiver operating characteristic plot with area under the curve (AUC), sensitivity and specificity. Finally, overrepresentation analysis was performed to assess if the best discriminating metabolites were enriched in specific metabolic events. Baseline concentrations of homocystine, taurine, adenosine triphosphate, guanosine diphosphate and uric acid were significantly lower in plasma of insufficient responders versus sufficient responders, while glycolytic intermediates 1,3-/2,3-diphosphoglyceric acid, glycerol-3-phosphate and phosphoenolpyruvate were significantly higher in insufficient responders. Homocystine, glycerol-3-phosphate and 1,3-/2,3-diphosphoglyceric acid were independent predictors and together showed a high AUC of 0.81 (95% CI: 0.72-0.91) for the prediction of insufficient response, with corresponding sensitivity of 0.78 and specificity of 0.76. The Warburg effect, glycolysis and amino acid metabolism were identified as underlying metabolic events playing a role in clinical response to MTX in early RA. New metabolites and potential underlying metabolic events correlating with MTX response in early RA were identified, which warrant validation in external cohorts.
32531990 Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Di 2020 Jun 10 Changes in the plasma metabolic profile were characterised in newly diagnosed rheumatoid arthritis (RA) patients upon commencement of conventional disease-modifying anti-rheumatic drug (cDMARD) therapy. Plasma samples collected in an early RA randomised strategy study (NCT00920478) that compared clinical (DAS) disease activity assessment with musculoskeletal ultrasound assessment (MSUS) to drive treatment decisions were subjected to untargeted metabolomic analysis. Metabolic profiles were collected at pre- and three months post-commencement of nonbiologic cDMARD. Metabolites that changed in association with changes in the DAS44 score were identified at the three-month timepoint. A total of nine metabolites exhibited a clear correlation with a reduction in DAS44 score following cDMARD commencement, particularly itaconate, its derived anhydride and a derivative of itaconate CoA. Increasing itaconate correlated with improved DAS44 score and decreasing levels of C-reactive protein (CRP). cDMARD treatment effects invoke consistent changes in plasma detectable metabolites, that in turn implicate clinical disease activity with macrophages. Such changes inform RA pathogenesis and reveal for the first time a link between itaconate production and resolution of inflammatory disease in humans. Quantitative metabolic biomarker-based tests of clinical change in state are feasible and should be developed around the itaconate pathway.
33252349 Machine Learning Electronic Health Record Identification of Patients with Rheumatoid Arthr 2020 Nov 30 BACKGROUND: Financial codes are often used to extract diagnoses from electronic health records. This approach is prone to false positives. Alternatively, queries are constructed, but these are highly center and language specific. A tantalizing alternative is the automatic identification of patients by employing machine learning on format-free text entries. OBJECTIVE: The aim of this study was to develop an easily implementable workflow that builds a machine learning algorithm capable of accurately identifying patients with rheumatoid arthritis from format-free text fields in electronic health records. METHODS: Two electronic health record data sets were employed: Leiden (n=3000) and Erlangen (n=4771). Using a portion of the Leiden data (n=2000), we compared 6 different machine learning methods and a naïve word-matching algorithm using 10-fold cross-validation. Performances were compared using the area under the receiver operating characteristic curve (AUROC) and the area under the precision recall curve (AUPRC), and F1 score was used as the primary criterion for selecting the best method to build a classifying algorithm. We selected the optimal threshold of positive predictive value for case identification based on the output of the best method in the training data. This validation workflow was subsequently applied to a portion of the Erlangen data (n=4293). For testing, the best performing methods were applied to remaining data (Leiden n=1000; Erlangen n=478) for an unbiased evaluation. RESULTS: For the Leiden data set, the word-matching algorithm demonstrated mixed performance (AUROC 0.90; AUPRC 0.33; F1 score 0.55), and 4 methods significantly outperformed word-matching, with support vector machines performing best (AUROC 0.98; AUPRC 0.88; F1 score 0.83). Applying this support vector machine classifier to the test data resulted in a similarly high performance (F1 score 0.81; positive predictive value [PPV] 0.94), and with this method, we could identify 2873 patients with rheumatoid arthritis in less than 7 seconds out of the complete collection of 23,300 patients in the Leiden electronic health record system. For the Erlangen data set, gradient boosting performed best (AUROC 0.94; AUPRC 0.85; F1 score 0.82) in the training set, and applied to the test data, resulted once again in good results (F1 score 0.67; PPV 0.97). CONCLUSIONS: We demonstrate that machine learning methods can extract the records of patients with rheumatoid arthritis from electronic health record data with high precision, allowing research on very large populations for limited costs. Our approach is language and center independent and could be applied to any type of diagnosis. We have developed our pipeline into a universally applicable and easy-to-implement workflow to equip centers with their own high-performing algorithm. This allows the creation of observational studies of unprecedented size covering different countries for low cost from already available data in electronic health record systems.
33488608 Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjö 2020 Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized primarily by immune-mediated destruction of exocrine tissues, such as those of the salivary and lacrimal glands, resulting in the loss of saliva and tear production, respectively. This disease predominantly affects middle-aged women, often in an insidious manner with the accumulation of subtle changes in glandular function occurring over many years. Patients commonly suffer from pSS symptoms for years before receiving a diagnosis. Currently, there is no effective cure for pSS and treatment options and targeted therapy approaches are limited due to a lack of our overall understanding of the disease etiology and its underlying pathology. To better elucidate the underlying molecular nature of this disease, we have performed RNA-sequencing to generate a comprehensive global gene expression profile of minor salivary glands from an ethnically diverse cohort of patients with pSS. Gene expression analysis has identified a number of pathways and networks that are relevant in pSS pathogenesis. Moreover, our detailed integrative analysis has revealed a primary Sjögren's syndrome molecular signature that may represent important players acting as potential drivers of this disease. Finally, we have established that the global transcriptomic changes in pSS are likely to be attributed not only to various immune cell types within the salivary gland but also epithelial cells which are likely playing a contributing role. Overall, our comprehensive studies provide a database-enriched framework and resource for the identification and examination of key pathways, mediators, and new biomarkers important in the pathogenesis of this disease with the long-term goals of facilitating earlier diagnosis of pSS and to mitigate or abrogate the progression of this debilitating disease.
31868853 The Association of Serum Vitamin D Level With the Severity of Dry Eye Parameters in Primar 2020 Jun PURPOSE: To analyze the relationship between serum 25(OH)D3 level and dry eye parameters in primary Sjögren syndrome (SS). METHODS: This study included 74 eyes of 74 patients diagnosed with primary SS. Dry eye parameters included tear breakup time, Schirmer I value, corneal staining score, conjunctival staining score, and Ocular Surface Disease Index. The serum concentration of 25(OH)D3 was evaluated. RESULTS: The mean serum 25(OH)D3 level was 20.4 ± 8.0 ng/mL. There were strong negative correlations between serum 25(OH)D3 level and corneal staining score (P < 0.001, r = -0.446) and conjunctival staining score (P < 0.001, r = -0.455). The Schirmer I value and tear breakup time showed significant positive correlations with serum 25(OH)D3 level (P = 0.038, r = 0.261 and P = 0.003, r = 0.352, respectively). The Ocular Surface Disease Index did not show any significant correlation with serum 25(OH)D3 level. CONCLUSIONS: This study demonstrates that serum 25(OH)D3 level might be associated with dry eye severity in primary SS.
31263993 Prescribing motivations and patients' characteristics related to the use of biologic drugs 2020 Jan A growing body of evidence suggests the usability of biologic disease-modifying anti-rheumatic drugs (bDMARDs) in treating adult-onset Still's disease (AOSD). In a multicentre "real-life" cohort, the physicians' prescribing motivations and patients' predictive characteristics of being treated with bDMARDs were assessed. Patients with AOSD, who were included in GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort and treated with bDMARDs, were retrospectively assessed. Relevant data were collected by a review of clinical charts. Forty-four patients treated with bDMARDs were analysed, with slight male preponderance (52.3%) and a mean age of 39.3 ± 15.2 years. All patients were treated with corticosteroids (CCSs) (38.6% with low dosage) and 93.2% were treated with synthetic DMARDs (sDMARDs). Regarding the effectiveness of the first-line bDMARD, 65.6% of patients experienced a complete remission, defined as complete disappearance of both systemic and joint symptoms and normalisation of laboratory evidence of disease. The physicians' prescribing motivations for bDMARDs were inadequate response to CCSs and/or sDMARDs, CCS-sparing effect and occurrence of macrophage activation syndrome (MAS). Analysing patients' characteristics, chronic disease course (OR 3.09; 95%CI 1.22-7.80, p = 0.017), defined as disease with persistent symptoms, was predictive of being treated with bDMARDs, whereas age (OR 0.97, 95%CI 0.93-0.99, p = 0.048) was negatively associated, suggesting younger age as a further predictive factor. Patients with AOSD were treated with bDMARDs for inadequate response to CCSs and/or sDMARDs, CCS-sparing effect and MAS occurrence. Younger age and chronic disease course were patients' predictive characteristics of being treated with bDMARDs.
32395427 Disseminated Neisseria gonorrhea of the wrist. 2020 Disseminated gonococcal infection (DGI) is seen in about 0.5-3% of patients with Neisseria gonorrhoeae. Patients with DGI present with mucosal involvement, septic arthritis and sometimes bacteremia. We present a case of a 62-year-old female with a history of HIV and rheumatoid arthritis admitted with DGI and septic arthritis of the wrist without mucosal involvement or systemic symptoms. The patient underwent incision and drainage with arthrotomy of the right wrist by hand surgery and received a 2-week course of intravenous ceftriaxone. After surgery and initiation of antibiotic treatment, there was marked improvement of her symptoms and she remains asymptomatic at follow-up.
33603736 Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4(+) T Lymphocytes and a L 2020 OBJECTIVE: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, and its pathogenetic mechanism is far from being understood. In this study, we aimed to explore the cellular and molecular mechanisms that lead to pathogenesis of this disease. METHODS: We applied single-cell RNA sequencing (scRNA-seq) to 57,288 peripheral blood mononuclear cells (PBMCs) from five patients with pSS and five healthy controls. The immune cell subsets and susceptibility genes involved in the pathogenesis of pSS were analyzed. Flow cytometry was preformed to verify the result of scRNA-seq. RESULTS: We identified two subpopulations significantly expand in pSS patients. The one highly expressing cytotoxicity genes is named as CD4(+) CTLs cytotoxic T lymphocyte, and another highly expressing T cell receptor (TCR) variable gene is named as CD4(+) TRAV13-2+ T cell. Flow cytometry results showed the percentages of CD4(+) CTLs, which were profiled with CD4(+) and GZMB(+) staining; the total T cells of 10 patients with pSS were significantly higher than those of 10 healthy controls (P= 0.008). The expression level of IL-1β in macrophages, TCL1A in B cells, as well as interferon (IFN) response genes in most cell subsets was upregulated in the patients with pSS. Susceptibility genes including HLA-DRB5, CTLA4, and AQP3 were highly expressed in patients with pSS. CONCLUSIONS: Our data revealed disease-specific immune cell subsets and provided some potential new targets of pSS. Specific expansion of CD4(+) CTLs may be involved in the pathogenesis of pSS, which might give valuable insights for therapeutic interventions of pSS.
33080444 Clinical significance of minor salivary gland biopsy in patients with idiopathic interstit 2020 Nov BACKGROUND: Significant overlap may occur between idiopathic interstitial pneumonia (IIP) and connective tissue diseases (CTDs) that do not meet the established classification criteria for any known CTDs (i.e., occult CTD). Performing minor salivary gland biopsy (MSGB) to detect occult primary Sjogren's syndrome (pSS) in IIP patients is not well studied. METHODS: Consecutive IIP patients underwent MSGB to determine the prevalence of positive MSGB findings. Furthermore, we characterised the clinical, physiological and serological profiles of the MSGB-positive patients. Cox regression models were used to identify independent predictors of survival. RESULTS: The data of 155 patients with IIP were available for analysis. Sixty patients (38.7%) had positive MSGB findings. Of them, the mean age was 63.3 years, 51.6% were women, usual interstitial pneumonia (UIP) was the predominant pattern (63.3%), and seronegative antibodies (61.6%) were likely. Patients with positive MSGB findings had significantly greater survival than those with negative MSGB findings (p = 0.041). After stratifying the MSGB cohort based on the presence of a UIP pattern, no significant difference in survival was noted between those with positive MSGB-UIP pattern and those with a negative MSGB-UIP pattern (p = 0.231). Multivariate analysis on all UIP patients showed that higher forced vital capacity (p = 0.010) and smoking status (p = 0.035) were independently associated with survival. CONCLUSIONS: A substantial number of IIP patients had underlying occult CTD, highlighting the importance of performing MSGB to identify the salivary component of pSS when evaluating patients with interstitial lung disease of undetermined aetiology.
33013884 Case Report: Adult Still's Disease in an Alemtuzumab-Treated Multiple Sclerosis Patient. 2020 BACKGROUND: Autoimmune adverse events are the most relevant risks of alemtuzumab therapy. We present a patient with relapsing-remitting multiple sclerosis, who developed adult-onset Still's disease (AOSD) following alemtuzumab treatment. CASE PRESENTATION: The patient suffered from sore throat, swallowing difficulties, high spiking quotidian fever, generalized skin rash, arthritis, and myalgia 2 months after the second course of alemtuzumab. Laboratory tests revealed elevated acute-phase reactants, anemia, neutrophilic leukocytosis, and thrombocytosis. Serum calprotectin, interleukin-2, and interleukin-6 levels were strongly increased. Autoimmune, rheumatic, neoplastic, infectious, and granulomatous disorders were excluded. The NLRP1 and NLRP3 gene test, which was performed under the presumption of a cryopyrin-associated autoinflammatory syndrome, was negative. Based on the Yamaguchi and Fautrel criteria, and supported by the histological findings from a skin biopsy of the rash, the diagnosis of AOSD was established. Therapy with the anti-IL-1 agent (anakinra) led to a significant improvement of symptoms and blood parameters. However, anakinra had to be converted to rituximab due to generalized drug eruption. Following therapy with rituximab, the patient has fully recovered. CONCLUSION: The current case highlights AOSD as another rare and potentially life-threatening secondary autoinflammatory/autoimmune event following alemtuzumab treatment.
32588976 Prevalence and risk factors of interstitial lung disease in patients with primary Sjögren 2020 Aug OBJECTIVE: To systematically review the prevalence and risk factors for interstitial lung disease (ILD) in patients with primary Sjögren's syndrome (pSS). METHODS: We searched PubMed, Embase, and Cochrane Library from inception to December 2019. Two investigators reviewed records according to predefined criteria. We calculated the pooled prevalence, weighted mean differences (WMDs), odds ratio (OR) and 95% confidence intervals (CIs) using a random effects model, and performed subgroup analysis, sensitivity analysis, and Egger's test. RESULTS: In 23 studies with 6157 pSS patients, the pooled prevalence of ILD in pSS patients was 13% (95% CI: 9-19). The pSS-ILD prevalence was higher in Asia (20%) than that in Europe (10%). Male gender (OR = 1.92, 95% CI: 1.26-2.95), elder age (WMD = 9.25 years, 95% CI: 2.78-15.72) and higher C-reactive protein (CRP) (WMD = 3.92 mg/L, 95% CI: 0.27-1.61) was associated with ILD in pSS patients. CONCLUSION: Interstitial lung disease was prevalent in pSS patients. Elder age, male gender and higher CRP were risk factors for pSS-ILD. Our data highlighted the importance of screening for ILD in high-risk pSS patients.
32968477 Haemophilus haemolyticus: an atypical pathogen of septic arthritis of the knee joint. 2020 Sep Septic knee arthritis is a common disease, mostly due to bacterial infections. We describe a rare case of Haemophilus haemolyticus causing unilateral septic arthritis of a native knee. The affected patient presented with persistent severe knee pain after repeated intra-articular injections. Patient history included knee arthroscopy and a known rheumatoid arthritis treated by steroids. Since conservative treatment was ineffective and infection could not be excluded, diagnostic arthroscopy was performed. Synovial fluid and biopsies verified the uncommon microorganism and antibiotic therapy was initiated. Clinical findings and blood results showed rapid improvement. The patient was discharged in a good condition after 6 weeks. A review of the current literature describes only one joint infection with H. haemolyticus as underlying cause. In immunocompromised patients with septic knee arthritis also atypical pathogens must be considered. Nevertheless, the established treatment algorithm with arthroscopy and anti-infective therapy seems to be effective leading to satisfactory results.
32232043 Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthrit 2020 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that may be associated with gut microbiota via the aryl hydrocarbon receptor (AhR). Human umbilical mesenchymal stem cells (HUMSCs) have therapeutic potential against RA, but the underlying mechanism has not been fully elucidated. The purpose of this study was to explore the mechanism of action of HUMSCs in rats with collagen-induced arthritis (CIA). METHOD: HUMSCs (1 × 10(6)) were transplanted into each rat with CIA. The tissue localization of HUMSCs and the therapeutic effects in the ankles were assessed. The immune status and expression of immune-related genes and proteins in related lymphoid tissues were subsequently tested. Furthermore, the levels of immune-related factors in serum and the changes in gut microbiota in the ileum were detected, and the levels of indole and their derivatives in plasma and the levels of AhR in the ileum were evaluated. RESULTS: HUMSCs homed to the popliteal lymph node (PLN), mesenteric lymph node (MLN), ankle cartilage, and ileum mucosa in rats with CIA. The transplantation of HUMSCs reduced the pathology scores and the degree of bone damage in the ankles. The immune status of T regulatory cells (Tregs) and T helper (Th)17 cells and the gene expression levels of interleukin (IL)-10, transforming growth factor (TGF)-β1, and IL-17A were altered in the PLN, which is the lymph tissue closest to the nidus, and the MLN, which is one of the gut-associated lymphoid tissues (GALTs). The proportion and function of B cells, Tregs, and Th17 cells were regulated in other GALTs, namely, Peyer's patches and the lamina propria. The gene expression of TGF-β1 and IL-17A and protein expression of IL-10, TGF-β1, IL-17A, IL-22, and immunoglobulin A (IgA) were modulated in the ileum, and the serum levels of IL-10, TGF-β1, IL-17A, IL-1β, and tumor necrosis factor (TNF)-α were regulated in the rats with CIA. The relative abundances of the genera Bacteroides and Bacillus were increased in the HUMSCs-treated rat with CIA; in addition, the levels of indole, indoleacetic acid, and indole-3-lactic acid were consistently upregulated, and this upregulation was accompanied by increases in AhR gene and protein expression. CONCLUSION: Our study demonstrates that HUMSCs play a therapeutic role in rats with CIA by regulating the interactions between host immunity and gut microbiota via the AhR.
33148700 Regulatory eosinophils induce the resolution of experimental arthritis and appear in remis 2020 Nov 4 OBJECTIVES: Eosinophils possess pro-inflammatory functions in asthma. However, our recent studies have suggested that innate lymphoid cells type 2 (ILC2s) and eosinophils have proresolving properties in rheumatoid arthritis (RA). Nothing is known yet about the mechanisms determining the double-edged role of eosinophils. Therefore, we investigated whether asthma, a paradigm eosinophilic disease, can elicit resolution of chronic arthritis. METHODS: Ovalbumin-triggered eosinophilic asthma was combined with K/BxN serum-induced arthritis, where lung and synovial eosinophil subsets were compared by single-cell RNA sequencing (scRNA-seq). To investigate the involvement of the ILC2-interleukin-5 (IL-5) axis, hydrodynamic injection (HDI) of IL-25 and IL-33 plasmids, IL-5 reporter mice and anti-IL-5 antibody treatment were used. In patients with RA, the presence of distinct eosinophil subsets was examined in peripheral blood and synovial tissue. Disease activity of patients with RA with concomitant asthma was monitored before and after mepolizumab (anti-IL-5 antibody) therapy. RESULTS: The induction of eosinophilic asthma caused resolution of murine arthritis and joint tissue protection. ScRNA-seq revealed a specific subset of regulatory eosinophils (rEos) in the joints, distinct from inflammatory eosinophils in the lungs. Mechanistically, synovial rEos expanded on systemic upregulation of IL-5 released by lung ILC2s. Eosinophil depletion abolished the beneficial effect of asthma on arthritis. rEos were consistently present in the synovium of patients with RA in remission, but not in active stage. Remarkably, in patients with RA with concomitant asthma, mepolizumab treatment induced relapse of arthritis. CONCLUSION: These findings point to a hitherto undiscovered proresolving signature in an eosinophil subset that stimulates arthritis resolution.
32066378 The impact of Clonorchis sinensis infection on immune response in mice with type II collag 2020 Feb 17 BACKGROUND: Clonorchis sinensis infection could trigger strong immune responses in mice and humans. However, whether the C.sinensis infection has an impact on arthritis is unknown. Here we investigated the effect of C.sinensis infection on type II collagen-induced arthritis in BALB/c mice. RESULTS: The mice were firstly infected with 45 C.sinensis metacercariae by oral gavage. Four weeks later, arthritis in mice was induced by type II collagen. Joint inflammation with severe redness and swelling in hind paws was observed in type II collagen-induced arthritis (CIA) mice. Besides, the physical activity was significantly reduced, but the respiratory exchange ratio was increased in CIA mice. Compared with CIA mice, C.sinensis infection could increase the severity of arthritis in CIA mice, based on the results of disease score and pathological changes. Compared to CIA mice, increased neutrophils and Ly6C(hi) monocytes, decreased B cells and CD4(+)T cells, were found in C.sinensis infected CIA mice. Besides these, C.sinensis infected mice also displayed significantly higher levels of serum IL-4 and IL-17 than those in CIA mice. CONCLUSIONS: Taken together, our data suggest that C.sinensis infection have a bad effect on arthritis, and could induce the abnormality of the immune response in mice with CIA.
33059968 Fingolimod reduces salivary infiltrates and increases salivary secretion in a murine Sjög 2020 Dec Sjögren's Syndrome (SjS) is a chronic, systemic autoimmune disease causing xerostomia, xerophthalmia, and systemic symptoms. The principal pathological finding in SjS is the accumulation of lymphocytes in exocrine glandular tissue and elsewhere, leading to secretory dysfunction and other abnormalities. A rational therapeutic approach might be to interfere with lymphocyte migration to the periphery from central lymphoid tissues. We thus examined in an animal model of SjS the effects of Fingolimod (FTY720, Gilenya™), which interferes with migration of lymphocytes to peripheral sites. Fingolimod induces sequestration of lymphocytes in lymphoid organs by altering lymphocyte expression of sphingosine-1-phosphate receptors. In the C57Bl/6. NOD.Aec1Aec2 (AEC) model of SjS, Fingolimod reduced circulating T and B cell numbers. Treatment of AEC mice with Fingolimod increased salivary output and decreased the size of salivary gland infiltrates. Oral Fingolimod thus merits further consideration in the management of SjS in humans.