Three cases of systemic lupus erythematosus presenting with ischemic stroke as the initial symptom: Case reports and literature review.

BACKGROUND: Ischemic stroke constitutes a grave complication within the context of systemic lupus erythematosus (SLE), typically manifesting several years postdiagnosis of SLE. Incidents where ischemic stroke precedes and acts as an initial symptom of SLE are comparatively rare in its early stages, and such presentations are frequently misdiagnosed as ischemic cerebrovascular diseases, posing significant diagnostic challenges. CASE REPORTS: This article presents three cases of young females in whom ischemic stroke emerged as the initial manifestation of SLE. It incorporates a review of 17 case reports published over the past two decades, focusing on patients with SLE where ischemic stroke was a primary symptom. This discussion encompasses the clinical presentation, outcomes, and therapeutic approaches for these patients. CONCLUSION: In young patients, particularly females presenting with ischemic stroke and especially in cases accompanied by hematologic or multisystemic involvement, there should be heightened vigilance for SLE-induced ischemic stroke. Early diagnosis and treatment significantly enhance patients' quality of life and survival rates.

A systemic lupus erythematosus patient with persistent elevated conjugated bilirubin as the initial symptom: A case report.

RATIONALE: While some systemic lupus erythematosus (SLE) patients may experience varying degrees of liver function abnormalities, only a small portion of these cases have clinical significance, and the majority of patients typically exhibit low levels of serum bilirubin. However, in this article, we present a case of a middle-aged female patient with SLE who exhibited persistent skin jaundice as her initial symptom, offering a fresh perspective on diagnosing and treating patients who exhibit unexplained liver dysfunction and SLE combined with liver injury. PATIENT CONCERNS: A 45-year-old woman was initially admitted to the hospital due to yellowing of the skin and sclera, and her symptoms did not improve significantly during treatment. The results were abnormal after relevant immunological tests. DIAGNOSES: Persistent non-conjugated bilirubin elevation due to lupus hepatitis. INTERVENTIONS: The use of methylprednisolone sodium succinate (40 mg/Qd) and mycophenolate mofetil (0.75 g/d) suppressed immunity, polyolefin choline (20 mL/d) and glutathione (0.6 g/Qd) improved liver function, and nutritional support therapy. OUTCOMES: After 2 weeks of treatment, a significant decrease in the yellow skin and sclera of the patient was observed. LESSONS: Most clinicians overlook that liver function abnormalities are the main manifestation of SLE, resulting in many patients not receiving timely treatment. This study highlights the importance that SLE is also a cause of abnormal liver function.

Aortic sinus aneurysm invading ventricular septum and dissection caused by Behcet's disease: a case report and literature review.

Few case reports have mentioned the aortic sinus aneurysm invading ventricular septum and dissection caused by Behcet's disease. Here, we reported a 36-year-old male patient with an aortic sinus aneurysm invading the ventricular septum and dissection caused by Behcet's disease, who manifested as recurrent chest tightness and shortness of breath. Cardiac ultrasound showed the rupture of the right aortic sinus and the formation of ventricular septal dissection. Ascending aortic valve prosthesis replacement, mitral valvuloplasty with ring implantation and tricuspid valvuloplasty were performed. Postoperatively, he was treated with hormones, hydroxychloroquine sulfate, mycophenolate mofetil tablets, thalidomide and warfarin, and his symptoms were relieved. This is a rare case easily being misdiagnosed and missed, early diagnosis and in-time treatment are crucial to avoid surgical complications. The diagnostic and therapeutic approaches of this patient were reported and related literature was reviewed in this case report.

Acyloxyacyl hydrolase promotes pulmonary defense by preventing alveolar macrophage tolerance.

Although alveolar macrophages (AMs) play important roles in preventing and eliminating pulmonary infections, little is known about their regulation in healthy animals. Since exposure to LPS often renders cells hyporesponsive to subsequent LPS exposures ("tolerant"), we tested the hypothesis that LPS produced in the intestine reaches the lungs and stimulates AMs, rendering them tolerant. We found that resting AMs were more likely to be tolerant in mice lacking acyloxyacyl hydrolase (AOAH), the host lipase that degrades and inactivates LPS; isolated Aoah-/- AMs were less responsive to LPS stimulation and less phagocytic than were Aoah+/+ AMs. Upon innate stimulation in the airways, Aoah-/- mice had reduced epithelium- and macrophage-derived chemokine/cytokine production. Aoah-/- mice also developed greater and more prolonged loss of body weight and higher bacterial burdens after pulmonary challenge with Pseudomonas aeruginosa than did wildtype mice. We also found that bloodborne or intrarectally-administered LPS desensitized ("tolerized") AMs while antimicrobial drug treatment that reduced intestinal commensal Gram-negative bacterial abundance largely restored the innate responsiveness of Aoah-/- AMs. Confirming the role of LPS stimulation, the absence of TLR4 prevented Aoah-/- AM tolerance. We conclude that commensal LPSs may stimulate and desensitize (tolerize) alveolar macrophages in a TLR4-dependent manner and compromise pulmonary immunity. By inactivating LPS in the intestine, AOAH promotes antibacterial host defenses in the lung.

Hemochromatosis as a secondary condition to systemic lupus erythematosus: A case report.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects multiple organs and systems, including joints, the cardiovascular system, lungs, skin, kidneys, the nervous system, and blood. The clinical presentations of SLE are diverse and vary widely. In this report, we present a case of a patient whose SLE was complicated by hemochromatosis to enhance clinicians' comprehension of this infrequent or rare complication of SLE. We aim to provide insights into the diagnosis and treatment processes of this condition.

Platycodin D relieves rheumatoid arthritis by promoting apoptosis of mitochondria to inhibit activation of hedgehog pathway.

Rheumatoid arthritis (RA) displays very similar characteristics to those of tumor cells, platycodin D (PD) is a triterpenoid saponin abundant in Platycodon grandiflorum (PG), plays an important role in the inhibition of tumor growth. Our previous experiments confirmed that PD inhibited MH7A cell proliferation and migration, but it's possible mechanism remain unclear. This study aimed to reveal the mechanism of PD on RA, based on network pharmacology analysis. Rat of CIA was treated with the different doses PD. The arthritis score and paw volume were evaluated, ankle imaging changes were observed via myosseous ultrasound, all rats were anaesthetized by intraperitoneal injection of 25% urethane (1 mL/100 g), and ankle histopathology was observed using hematoxylin and eosin (HE) staining. Cell (MH7A) Counting Kit 8 (CCK8) was used to measure cell activity, and JC-1 assay kit and flow cytometry were employed to examine the cell mitochondrial membrane potential and apoptosis. The expression levels of Sonic hedgehog (Shh) signaling pathway-related proteins were observed by Western blotting. Cell inflammation levels of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 being determined via enzyme-linked immunoassay ELISA and q-PCR. In total, the saponin PD significantly improves joint synovium inflammation and apoptosis in CIA rats. The activity of administered MH7A was significantly inhibited, the mitochondrial membrane potential decreased, the expression level of the Shh signaling pathway-related protein SuFu increased, the expression levels of SHh and Gli decreased, and cell serum levels of TNF-a and IL-6 decreased significantly. Therefore, PD exhibits therapeutic potential for synovial hyperplasia in RA.

Predictors of response of rituximab in rheumatoid arthritis by weighted gene co-expression network analysis.

PURPOSE: The purpose of this study was to identify a biomarker that can predict the efficacy of rituximab (RTX) in the treatment of rheumatoid arthritis (RA) patients. METHODS: Utilized weighted gene co-expression network analysis (WGCNA) and LASSO regression analysis of whole blood transcriptome data (GSE15316 and GSE37107) related to RTX treatment for RA from the GEO database, the critical modules, and key genes related to the efficacy of RTX treatment for RA were found. The biological functions were further explored through enrichment analysis. The area under the ROC curve (AUC) was validated using the GSE54629 dataset. RESULTS: WGCNA screened 71 genes for a dark turquoise module that were correlated with the efficacy of RTX treatment for RA (r = 0.42, P < 0.05). Through the calculation of gene significance (GS) and module membership (MM), 12 important genes were identified; in addition, 21 important genes were screened by the LASSO regression model; two key genes were obtained from the intersection between the important genes. Then, BANK1 (AUC = 0.704, P < 0.05) was identified as a potential biomarker to predict the efficacy of RTX treatment for RA by ROC curve evaluation of the treatment and validation groups. BANK1 gene expression was significantly decreased after RTX treatment, and a statistically significant difference was found (log FC = - 2.08, P < 0.05). Immune cell infiltration analysis revealed that the infiltration of CD4 + T cell memory subset was increased in the group with high BANK1 expression, and a statistically significant difference was found (P < 0.05). CONCLUSIONS: BANK1 can be used as a potential biomarker to predict the response of RTX treatment in RA patients. Key Points • Identifying the hub genes BANK1 as a potential biomarker to predict the response of RTX treatment in RA patients and confirming it in validation data. • Using the WGCNA approach and LASSO analyses to identify the BANK1 in a data set consisting of two GEO data merged and assessing the correlations between BANK1 and immune infiltration by CIBERSORT algorithm.

Case Report: Vesicorectal Fistula Caused by Intestinal Tuberculosis Complicated with Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) are prone to various infections due to autoimmune defects and long-term use of immunosuppressive agents. Mycobacterium tuberculosis (TBC) infection is a common infection in patients with SLE, especially in developing countries such as China. SLE and TBC may overlap and confuse a clinical picture, bringing great difficulties for the diagnosis and treatment. This article reports a case of vesicorectal fistula caused by intestinal TBC complicated with SLE, where the manifestation was recurrent diarrhea, initially treated as lupus-associated intestinal vasculitis without notable response. This case suggests that we should pay attention to close monitoring of tuberculosis-related indicators during the follow-up period of SLE patients, especially in endemic areas, and early diagnosis and treatment of TBC can reduce tuberculosis-related complications and significantly improve the quality of life of patients.

SLAMF8 promotes the proliferation and migration of synovial fibroblasts by regulating the ERK/MMPs signalling pathway.

Rheumatoid arthritis is troublesome to treat effectively and often requires concomitant long-term treatment. Meanwhile, synovial fibroblasts could induce inflammation response and lead to joint erosion, finally causing progressive joint destruction, disability, and increased mortality. This study focussed on the role of SLAM family member 8 (SLAMF8) in mediating cell function from rheumatoid arthritis synovial fibroblasts stimulated with TNF-α. Cell Counting Kit-8 (CCK-8) and colony-forming unit assay were used to evaluate cell proliferation. SLAMF8 expression was analysed by reverse transcription-quantitative PCR (RT-qPCR) and western blot. Annexin V-FITC/PI double staining was used to measure the apoptosis rate. The cell migration and invasion in TNF-α-stimulated MH7A (human rheumatoid arthritis synovial cell line) and HFLS-RA cells (human fibroblast-like synoviocytes: rheumatoid arthritis) were tested via wound healing assay and transwell migration assay. In the present study, after TNF-α treatments, the SLAMF8 mRNA and protein expression in both MH7A and HFLS-RA cell lines have a time-dependent increase. The attenuation of SLAMF8 ameliorated TNF-α-induced proliferation, invasion and migration in MH7A and HFLS-RA cells. Simultaneously, when SLAMF8 was silenced, the expression of p-ERK, MMP-1, and MMP-13 was suppressed significantly. In summary, these results indicated that the knockdown of the SLAMF8 significantly attenuated TNF-α-induced proinflammatory responses in MH7A and HFLS-RA cells. Therefore, SLAMF8 exhibits therapeutic potential for the management of inflammation in rheumatoid arthritis.

Linkage of calprotectin with inflammation, activity and treatment response of rheumatoid arthritis: a meta-analysis.

Aim: This meta-analysis aimed to investigate the clinical value of calprotectin in rheumatoid arthritis (RA) patients. Methods: The data regarding blood calprotectin levels in RA patients were retrieved from PubMed, Embase, Web of Science and Cochrane databases. Results: Thirty-one eligible articles were included. Calprotectin was increased in RA patients compared with healthy controls (mean difference [MD] = 1.48, 95% CI: 1.16-1.79). Calprotectin was positively associated with C-reactive protein (correlation coefficient [CC] = 0.58, 95% CI: 0.53-0.63) and disease activity score (CC = 0.48, 95% CI: 0.38-0.58) in RA patients. Interestingly, calprotectin showed an increased trend in RA responders compared with nonresponders, but without statistical significance (MD = 0.38, 95% CI: -0.09-0.85). Conclusion: Blood calprotectin relates to disease risk, inflammation and activity in RA patients.

This meta-analysis included published data about blood calprotectin levels in rheumatoid arthritis (RA) patients. After integrated analyses, it was observed that blood calprotectin levels were higher in RA patients compared with healthy subjects; calprotectin was positively related to systemic inflammation and disease activity in RA patients. However, blood calprotectin levels failed to predict treatment outcomes in RA patients.

Identification and Validation of ATF3 Serving as a Potential Biomarker and Correlating With Pharmacotherapy Response and Immune Infiltration Characteristics in Rheumatoid Arthritis.

Background: Although disease-modifying antirheumatic drugs (DMARDs) have significantly improved the prognosis of patients with rheumatoid arthritis (RA), approximately 40% of RA patients have limited response. Therefore, it was essential to explore new biomarkers to improve the therapeutic effects on RA. This study aimed to develop a new biomarker and validate it by an in vitro study. Methods: The RNA-seq and the clinicopathologic data of RA patients were downloaded from Gene Expression Omnibus (GEO) databases. Differentially expressed genes were screened in the GPL96 and GPL570 databases. Then, weighted gene co-expression network analysis (WGCNA) was used to explore the most correlated gene modules to normal and RA synovium in the GPL96 and GPL570 databases. After that, the differentially expressed genes were intersected with the correlated gene modules to find the potential biomarkers. The CIBERSORT tool was applied to investigate the relationship between activated transcription factor 3 (ATF3) expression and the immune cell infiltration, and Gene Set Enrichment Analysis (GSEA) was used to investigate the related signaling pathways of differentially expressed genes in the high and low ATF3 groups. Furthermore, the relationships between ATF3 expression and clinical parameters were also explored in the GEO database. Finally, the role of ATF3 was verified by in vitro cell experiments. Results: We intersected the differentially expressed genes and the most correlated gene modules in the GPL570 and GPL96 databases and identified that ATF3 is a significant potential biomarker and correlates with some clinical-pharmacological variables. Immune infiltration analysis showed that activated mast cells had a significant infiltration in the high ATF3 group in the two databases. GSEA showed that metabolism-associated pathways belonged to the high ATF3 groups and that inflammation and immunoregulation pathways were enriched in the low ATF3 group. Finally, we validated that ATF3 could promote the proliferation, migration, and invasion of RA fibroblast-like synoviocyte (FLS) and MH7A. Flow cytometry showed that ATF3 expression could decrease the proportion of apoptotic cells and increase the proportion of S and G2/M phase cells. Conclusion: We successfully identified and validated that ATF3 could serve as a novel biomarker in RA, which correlated with pharmacotherapy response and immune cell infiltration.

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis.

BACKGROUND: Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development. METHODS: We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression. RESULTS: A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001). CONCLUSION: As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.

Vitamin D-Binding Protein Is a Potential Urinary Biomarker of Irbesartan Treatment Response in Patients with IgA Nephropathy.

AIMS: The purpose of this study was to identify predictive markers of irbesartan (an angiotensin receptor blocker) treatment response in immunoglobulin A nephropathy (IgAN) patients. METHODS: Urine samples were collected both before and after irbesartan treatment in IgAN patients and compared with urine from healthy volunteers. The total urinary protein produced in 24 h was measured to determine therapeutic response. The urinary proteome was evaluated by two-dimensional gel electrophoresis coupled with MALDI-TOF-MS/MS analysis. Western blotting was used to verify protein expression. A receiver operating characteristic curve was used to evaluate the sensitivity and specificity of candidate biomarkers. RESULTS: Four differentially expressed proteins were identified as vitamin D-binding proteins (VDPs). Western blot showed that urinary VDPs were significantly elevated in nonresponsive versus responsive IgAN patients. The sensitivity, specificity, and accuracy of urinary VDP as a predictive biomarker of irbesartan nonresponsiveness in IgAN were 65%, 85%, and 75%, respectively. CONCLUSION: Our results revealed that urinary VDP might be a useful biomarker for predicting irbesartan treatment response.

Inhibition of GSK-3ß Alleviates Collagen II-Induced Rheumatoid Arthritis in Rats.

BACKGROUND: Glycogen synthase kinase-3ß (GSK-3ß) inhibitor is a serine/threonine kinase with an inhibitory role in glycogen synthesis, which is essential in inflammatory and immunological diseases. The purpose of our study was to determine if TDZD-8 can alleviate collagen II-induced rheumatoid arthritis in rats. MATERIAL/METHODS: Twenty collagen II-induced rheumatoid arthritis rats were treated with selective GSK-3ß inhibitor. The effects of GSK-3ß inhibition on collagen II-induced rheumatoid arthritis in the rats were evaluated by paw edema, histological examination of arthritic synovium, radiographic examination of knee joint, and the level of inflammation mediators such as prostaglandin E2, 5-hydroxytryptamin, and histamine. The level of cytokines such as IL-6, IL-12, IL-10, and TNF-α, was examined by Elisa. RESULTS: GSK-3ß inhibitor significantly reduced the development of rheumatoid arthritis in rats. The levels of inflammation mediators such as prostaglandin E2, 5-hydroxytryptamin, and histamine were decreased in the TDZD-8 group. Serum levels of IL-6, IL-12, and TNF-α were significantly reduced in the TDZD-8 group compared with the RA group. CONCLUSIONS: Treatment with GSK-3ß inhibitor suppressed inflammatory response in RA rats. These findings suggest that the inhibition of GSK-3ß can be an effective treatment for RA.