Autoimmune Connective Tissue Disease Research Articles

Ocular Manifestation in Systemic Sclerosis—A Literature Review

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease that affects more than 2 million people worldwide. It manifests through vasculopathy, an abnormal immunological response, and fibrosis leading to dysfunction of the multiple organs. The disease is categorized into two subtypes: limited cutaneous SSc and diffuse cutaneous SSc. Scleroderma can affect vital organs with respiratory, cardiac, renal, ocular, and dermatological complications. The ocular manifestations of the disease can occur in the anterior and posterior segments of the eye. Changes in the anterior segment related to the disease include eyelid skin remodeling, dry eye syndrome, and conjunctival abnormalities. The disease’s impact on the posterior segment of the eye mostly causes pathologies in the retinal microcirculatory system and abnormalities in the optic nerve. This review provides detailed insights into ocular complications associated with scleroderma.

Intestinal pseudo-obstruction as systemic lupus erythematosus complication: is it time to reconsider the role of surgery?: A case report of a tailored multidisciplinary managed 44-year-old male patient

Rationale: Intestinal pseudo-obstruction (IPO) represents an unclarified dysmotility disorder characterized by clinic-radiological signs of intestinal obstruction not associated with organic conditions. IPO may occur as a rare complication of autoimmune connective tissue diseases, including Systemic Lupus Erythematosus (SLE). Surgery is recognized as having a marginal management position for IPO patients: this case investigates its role, in the context of a multidisciplinary approach, in the diagnosis and treatment of acute complications of IPO. Patient concerns: An SLE-affected 44-year-old man with a history of recurring nonspecific abdominal sub-obstructive episodes was admitted to our department for constipation, vomiting, and unintentional weight loss. Clinical examination revealed a family history of eosinophilic gastroenteritis (EG). Laboratory tests, including Systemic Sclerosis screening, presented no significant alterations. Abdominal X-ray highlighted multiple air-fluid levels; contrast-enhanced CT showed fluid surrounding dilated loops, and fluid-filled ileal loops, without evidence of organic intrinsic/ab-extrinsic obstruction, perforation, or extraluminal gas. Considering these findings, stenosing-pattern Crohn disease and strictures-complicated EG were mainly suspected. However, ileum-colonoscopy with the histological analysis resulted in inconclusive for Crohn disease and EG. Diagnosis: The histological examination, by showing an SLE fibro-inflammatory pattern, not sparing the enteric plexus, infiltrating the intestinal wall of the surgical samples collected during the right hemicolectomy intervention, allowed the diagnosis of IPO. Interventions and outcomes: The patient, indeed, was initially managed conservatively with nasogastric decompression, immunosuppressive therapy, and parenteral nutrition by a multidisciplinary team including gastroenterologists, rheumatologists, and nutritionists. Unfortunately, 2 weeks later, the worsening symptoms required a lifesaving right hemicolectomy followed by ileostomy. Lessons: IPO should be suspected in SLE patients presenting treated-unresponsive GI symptoms. Its early recognition finalized to start a tailored multidisciplinary approach appears prognostically crucial. Surgery could represent a paramount diagnostic moment and therapeutic life-saving approach.

Pattern of Autoimmune Connective Tissue Diseases Among Patients Attending Al-Thawra Teaching General Hospital, Sana'a-Yemen

Background: Connective tissue is also called connectivum. Many autoimmune diseases affect the connective tissue and blood vessels, are often referred to as connective tissue disorders. Autoimmune diseases currently are estimated to affect 2-5% of the population in the developed countries. Aim: The aim of this study was to determine the pattern of autoimmune inflammatory connective tissue diseases among patients attending Al-Thawra teaching general hospital, Sana'a-Yemen. Method: This study is observational prospective study conducted at Al-Thawra hospital, Sana'a-Yemen, department of internal medicine, duration of the study was 12 months. Sample size was 137. Results: The results showed that systemic lupus erythematosus, antiphospholipid syndrome and rheumatoid arthritis have the highest prevalence. The main clinical presentations are arthritis, leg swelling and dyspnea. The main drugs used are corticosteroids, low molecular weight heparin, and rituximab. The proportion of females to males is 3.55 to 1. The age range 20 – 30 years is the highest representing 47% of the total patients. Patients from Sana'a, Taiz, and Ibb being the most common. Illiterates represent 63%, housewives represent 72% of the total patients. Conclusion: We conclude that autoimmune connective tissue diseases affect 8% of the total patients admitted to the internal medicine department. SLE is the most common autoimmune connective tissue disease encountered and represents 43% of total cases. Arthritis and leg swelling are the most common clinical presentations encountered; both represents 48% of the total presentations. Corticosteroids are the most common prescribed drugs, 45%. The aetiology of autoimmune connective tissue diseases is still not fully known. Immuno-modulators are needed to regulate the immune system. Physiotherapy is recommended beside medical therapy.

ВЛИЯНИЕ РЕВМАТОИДНОГО АРТРИТА НА ТЕЧЕНИЕ ЗАБОЛЕВАНИЙ ПАРОДОНТА

The most common chronic systemic autoimmune disease of connective tissue is rheumatoid arthritis, the incidence of which is up to 50% (in Russia). The etiology of rheumatoid arthritis is still not known for certain. Scientists pay special attention to searching and studying the factors influencing the occurrence of this disease. Researchers are interested in periodontitis as a likely factor in the development of rheumatoid arthritis. The literature presents limited data on the study of the characteristics of the course of dental diseases in patients with rheumatoid arthritis, which indicates the need for further study of this issue and clarification of the relationships between the intensity of caries, the condition of periodontal tissues and the temporomandibular joint in this category of patients. The study of these issues is of scientific and practical interest, as it allows us to improve the methods of diagnosis and monitoring of patients with rheumatoid arthritis by a dentist. The purpose of this study is to determine the effect of rheumatoid arthritis on the course of periodontal diseases. Materials and methods. The methodology of the scientific research is based on the analysis of domestic and foreign literature in the eLIBRARY databases; basic and additional methods of examining the patient were carried out. During the clinical examination, we assessed the general condition of the patient with rheumatoid arthritis, his dental and periodontal status. Results and discussion. A clinical examination of a patient with somatic pathology was carried out. Microorganisms of periodontal pockets were determined, the data obtained were compared with a patient who does not have a systemic disease. Conclusions. Patients with rheumatoid arthritis generally have a thin gingival biotype. Immunological parameters of oral fluid (IgA) in rheumatoid arthritis decrease, which indicates a lack of local and general immunity and leads to damage to periodontal tissue. In the future, this scientific research will help us develop optimal methods for diagnosing and treating patients with autoimmune disease.

De novo autoimmune connective tissue disease and mortality in patients treated with anti-PD-1 and anti-PD-L1 therapy: a population-level cohort study.

Using a population-level cohort analysis, our study demonstrates that though rare, de novo autoimmune cutaneous connective tissue disorders (AiCTD) in the setting of immune checkpoint inhibitors (ICI) are not associated with a greater risk of mortality and are overall approaching a statistically significant decrease in mortality when compared to ICI-treated patients without cutaneous immune-related adverse events. These findings are significant and highly relevant to dermatologists and oncologists caring for ICI recipients as it adds to the limited information on development of cutaneous AiCTD following ICI administration, for which enhanced understanding is critical to improving the care for this challenging patient population.

E001 Pre-screen chest X-ray before starting methotrexate in autoimmune disease

Abstract Background/Aims This audit seeks to assess adherence to BSR guidelines and NICE recommendations concerning chest X-ray screening before initiating methotrexate. We also aim to evaluate the time elapsed from X-ray to radiologist reporting and the frequency of methotrexate initiations for various diagnoses. Methods We identified 127 cases from the rheumatology department (2017-2021) involving patients aged 18 or older with diagnoses of rheumatoid arthritis, psoriatic arthritis, lupus, or autoimmune connective tissue disease. We checked patient records for evidence of pre-treatment chest X-rays Results Rheumatoid arthritis was the most common diagnosis for methotrexate initiation. Out of the 127 patients, 102 underwent chest X-rays (80%), while 23 did not. For 2 patients, the status of chest X-ray performance remained unknown. The breakdown of percentages by hospital was as follows: QEQM (87%), WHH (70%), KCH (77%). The distribution of report times across the three hospitals was as follows: 1-7 days (52%), 8-14 days (4%), 15-31 days (12%), 32-62 days (11%), 63-100 days (15%), 101+ days (6%). Conclusion Urgent reporting of chest X-rays is imperative. Proposed solutions include flagging X-rays as urgent by incorporating a 'Patient starting Methotrexate?’ query. If selected 'yes’ this would flag the report as urgent on the Soliton system. This allows for prompt reporting of these X-rays with timely starting of the DMARDs treatment in various autoimmune conditions. This was done as beforehand, X-rays were not reported in a prompt manner even if they were stated as urgent in the requests. A smaller post-audit analysis involving 15 patients achieved 100% compliance of reporting within one week by implementing these changes. Disclosure M.A. Khan: None. A. Khan: None. A. Vijayan: None. A. Hajilou: None. M. Win: None.

P147 M2 macrophage associated fibrosis in early stage systemic sclerosis: an update on plasma biomarkers

Abstract Background/Aims Systemic sclerosis is an autoimmune connective tissue disease characterised by vasculopathy and fibrosis. The CCN family of matricellular proteins have a regulatory role in inflammation and fibrosis. CD206, an M2 macrophage surface marker, is cleaved by metalloproteases to release soluble form of CD206; this acts as an active disease marker in systemic sclerosis. We investigated the profile of CCN2 and CCN3 in the presence of soluble CD206 (sCD206) in patients with early and late stage diffuse systemic sclerosis (dcSSc). Methods Patients with a diagnosis of dcSSc at the UCL Centre for Rheumatology and Connective Tissue Diseases were recruited. Informed consent was obtained from patients and healthy controls (HC). Blood samples were taken from which plasma was isolated and stored at -80 °C prior to assay. Expression of CCN2, CCN3, and sCD206 was measured in these plasma samples by ELISA. Study participants were categorised into healthy controls (n = 20), early stage dcSSc (n = 20) and late dcSSc (n = 20), with early stage defined as the blood sample taken within two years since diagnosis, and late stage defined as over five years since diagnosis. Results Plasma CCN2, CCN3 and sCD206 levels were significantly higher in early dcSSc patients, when compared to HC. CCN2 was raised in early dcSSc patients (early dcSSc mean 20,221pg/ml, SD 16,503, p < 0.05) with concentration in late disease matching that of HC (late dcSSc 12,893pg/ml, HC 11,289pg/ml). CCN3 was significantly higher in early and late disease when compared to HC (early mean 16,526pg/ml, late 12,838pg/ml, HC 4,201pg/ml, p < 0.05). sCD206 levels were higher in early dcSSc (mean 5356pg/ml, SD 3154, p < 0.05), with there being no significance between levels in late dcSSc (mean 4184pg/ml, SD 3900, p > 0.05) and HC (mean 3319pg/ml, SD 1925). CCN2 expression was higher compared to that of CCN3 in early disease, with CCN2:CCN3 ratio elevated in early dcSSc (mean 3.17, SD 8.26) compared to late dcSSc (mean 1.26, SD 0.99) and HC. Conclusion This investigation demonstrates that upregulation of CCN2 and CCN3 expression has a regulatory role in fibrosis in early stage dcSSc. These biomarkers of M2 macrophage associated fibrosis are to be correlated with their clinical phenotype and have potential for a role in targeted treatment of systemic sclerosis. Disclosure L.A. Leeves: None. Z. Kannan: None. Y. Ali: None. L. Pan: None. T. Malley: None. D. Abraham: None. A. Leask: None. B. Riser: None. B. Ahmed Abdi: None. R.J. Stratton: None.

Pathologic Features of Anti-Ku Myositis.

Characteristics of myositis with anti-Ku antibodies are poorly understood. The purpose of this study was to elucidate the pathologic features of myositis associated with anti-Ku antibodies, compared with immune-mediated necrotizing myopathy (IMNM) with anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, in muscle biopsy-oriented registration cohorts in Japan and Germany. We performed a retrospective pathology review of patients with anti-Ku myositis samples diagnosed in the Japanese and German cohorts. We evaluated histologic features and performed HLA phenotyping. Fifty biopsied muscle samples in the Japanese cohort and 10 in the German cohort were obtained. After exclusion of myositis-specific autoantibodies or other autoimmune connective tissue diseases, 26 samples (43%) of anti-Ku antibody-positive myositis were analyzed. All the samples shared some common features with IMNM, whereas they showed expression of MHC class II and clusters of perivascular inflammatory cells more frequently than the anti-SRP/HMGCR IMNM samples (71% vs 7%/16%; p < 0.005/<0.005; 64% vs 0%/0%; p < 0.005/<0.005). Anti-Ku myositis biopsies could be divided into 2 subgroups based on the extent of necrosis and regeneration. The group with more abundant necrosis and regeneration showed a higher frequency of MHC class II expression and perivascular inflammatory cell clusters. HLA phenotyping in the 44 available patients showed possible associations of HLA-DRB1*03:01, HLA-DRB1*11:01, and HLA-DQB1*03:01 (p = 0.0045, 0.019, and 0.027; odds ratio [OR] 50.2, 4.6, and 2.8; 95% CI 2.6-2942.1, 1.1-14.5, and 1.0-7.0) in the group with less conspicuous necrosis and regeneration. On the contrary, in the group of more abundant necrosis and regeneration, the allele frequencies of HLA-A*24:02, HLA-B*52:01, HLA-C*12:02, and HLA-DRB1*15:02 were lower than those of healthy controls (p = 0.0036, 0.027, 0.016, and 0.026; OR = 0.27, 0, 0, and 0; 95% CI 0.1-0.7, 0-0.8, 0-0.8, and 0-0.8). However, these HLA associations did not remain significant after statistical correction for multiple testing. While anti-Ku myositis shows necrotizing myopathy features, they can be distinguished from anti-SRP/HMGCR IMNM by their MHC class II expression and clusters of perivascular inflammatory cells. The HLA analyses suggest that anti-Ku myositis may have different subsets associated with myopathologic subgroups.

Antinuclear antibody (ANA) positivity pattern by line immunoassay in a hospital from eastern India: Update from a laboratory perspective

ABSTRACT Context: The existence of more than one antibody in systemic autoimmune rheumatic diseases (SARDs) or connective tissue disease (CTD) along with features of more than one autoimmune disease (AD) in an individual is suggestive of overlap syndrome (OS). Line immunoassay (LIA) can target many autoantibodies in a single approach, thus making the identification of OS feasible. Aims and Objectives: This study aimed to identify the pattern of distribution of antinuclear antibodies by LIA prevalent in a hospital population in eastern India and identify common forms of SARD in this belt based on laboratory findings. Material and Methods: A total of 1660 samples received for ANA profile testing by LIA were analysed. Statistical Analysis: Factor analysis was performed with factor loading scores used in the k-means algorithm to identify clustering of various autoantibodies. Results: U1-snRNP positivity was the highest at 16.69%, and the least frequent autoantibody noted was anti-Jo-1 at 0.71% positivity. Based on the outcome of factor analysis, three clusters were determined. Cluster 1 showed a predominance of anti-PM/Scl antibodies, cluster 2 showed a predominance of anti-dsDNA, anti-histone, anti-SmD1, anti-nucleosomes, anti-PCNA, anti-Po, anti-SSA/Ro52, anti-SSA-Ro60, anti-SSB/La, anti-Scl-70, anti-Mi-2, anti-Ku and anti-AMA-M2, and cluster 3 showed a predominance of anti-U1-snRNP. Conclusions: Mixed connective tissue disease (MCTD) and overlap syndrome (OS) are prevalent more than pure form of an AD in our study population. OS may be missed out by monospecific immunoassays and hence adds to diagnostic challenges. LIA may be more useful in identifying specific autoantibodies by a single approach rather than monospecific immunoassays in populations after a positive screen by indirect immunofluorescence (IIF).

Distinctive profile of monomeric and polymeric anti-SSA/Ro52 immunoglobulin A1 isoforms in saliva of patients with primary Sjögren’s syndrome and Sicca

ObjectivePrimary Sjögren’s syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is...

Nintedanib downregulates the profibrotic M2 phenotype in cultured monocyte-derived macrophages obtained from systemic sclerosis patients affected by interstitial lung disease

BackgroundSystemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of skin and several internal organs, including lungs. Macrophages are the main cells involved in the immune-inflammatory damage of skin and lungs, and alternatively activated (M2) macrophages seem to have a profibrotic role through the release of profibrotic cytokines (IL10) and growth factors (TGFβ1). Nintedanib is a tyrosine kinase inhibitor targeting several fibrotic mediators and it is approved for the treatment of SSc-related interstitial lung disease (ILD). The study aimed to evaluate the effect of nintedanib in downregulating the profibrotic M2 phenotype in cultured monocyte-derived macrophages (MDMs) obtained from SSc-ILD patients.MethodsFourteen SSc patients, fulfilling the 2013 ACR/EULAR criteria for SSc, 10 SSc patients affected by ILD (SSc-ILD pts), 4 SSc patients non affected by ILD (SSc pts no-ILD), and 5 voluntary healthy subjects (HSs), were recruited at the Division of Clinical Rheumatology-University of Genova, after obtaining Ethical Committee approval and patients’ informed consent. Monocytes were isolated from peripheral blood, differentiated into MDMs, and then maintained in growth medium without any treatment (untreated cells), or treated with nintedanib (0.1 and 1µM) for 3, 16, and 24 h. Gene expression of macrophage scavenger receptors (CD204, CD163), mannose receptor-1 (CD206), Mer tyrosine kinase (MerTK), identifying M2 macrophages, together with TGFβ1 and IL10, were evaluated by quantitative real-time polymerase chain reaction. Protein synthesis was investigated by Western blotting and the level of active TGFβ1 was evaluated by ELISA. Statistical analysis was carried out using non-parametric Wilcoxon test.ResultsCultured untreated SSc-ILD MDMs showed a significant increased protein synthesis of CD206 (p < 0.05), CD204, and MerTK (p < 0.01), together with a significant upregulation of the gene expression of MerTK and TGFβ1 (p < 0.05; p < 0.01) compared to HS-MDMs. Moreover, the protein synthesis of CD206 and MerTK and the gene expression of TGFβ1 were significantly higher in cultured untreated MDMs from SSc-ILD pts compared to MDMs without ILD (p < 0.05; p < 0.01). In cultured SSc-ILD MDMs, nintedanib 0.1 and 1µM significantly downregulated the gene expression and protein synthesis of CD204, CD206, CD163 (p < 0.05), and MerTK (p < 0.01) compared to untreated cells after 24 h of treatment. Limited to MerTK and IL10, both nintedanib concentrations significantly downregulated their gene expression already after 16 h of treatment (p < 0.05). In cultured SSc-ILD MDMs, nintedanib 0.1 and 1µM significantly reduced the release of active TGFβ1 after 24 h of treatment (p < 0.05 vs. untreated cells).ConclusionsIn cultured MDMs from SSc-ILD pts, nintedanib seems to downregulate the profibrotic M2 phenotype through the significant reduction of gene expression and protein synthesis of M2 cell surface markers, together with the significant reduction of TGFβ1 release, and notably MerTK, a tyrosine kinase receptor involved in lung fibrosis.

Emerging therapeutic targets in systemic sclerosis.

Systemic sclerosis is an autoimmune connective tissue disease which is characterised by vascular perturbations, inflammation, and fibrosis. Although huge progress recently into the underlying molecular pathways that are perturbed in the disease, currently no therapy exists that targets the fibrosis element of the disease and consequently there is a huge unmet medical need. Emerging studies reveal new dimensions of complexity, and multiple aberrant pathways have been uncovered that have shed light on disturbed signalling in the disease, primarily in inflammatory pathways that can be targeted with repurposed drugs. Pre-clinical animal models using these inhibitors have yielded proof of concept for targeting these signalling systems and progressing to clinical trials. This review will examine the recent evidence of new perturbed pathways in SSc and how these can be targeted with new or repurposed drugs to target a currently intractable disease.

Relationship between ultrasound imaging of dorsalis pedis artery and foot health symptoms in people with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is an autoimmune connective tissue disease which affects joint function and multiple body systems. Poor foot health for people with RA has a negative impact on mobility, functional capacity, and quality of life. Additional to joint pain, people with RA may develop vascular disease e.g., vasculitis, which can have increasingly detrimental effects on foot health, quality of life and longevity. If identified early, adverse effects may be prevented. However, the link between foot health symptoms and ultrasound identified precursory changes for vasculitis is yet to be established. ObjectivesThis study aimed to examine the association between foot health symptoms and the integrity of the dorsalis pedis artery (DPA). MethodsWe recruited 47 participants with RA and 47 characteristic-matched controls. All participants completed an online survey which included demographic questions and Foot Health Status Questionnaire (FHSQ). Ultrasound imaging measured participants’ proximal DPA in terms of degree of wall inflammation, lumen diameter, artery diameter, lumen-to-artery diameter ratio and peak systolic velocity. ResultsSignificant differences (p < 0.001) were noted between groups for degree of wall inflammation, artery diameter and lumen to artery diameter ratio, while lumen diameter and peak systolic velocity demonstrated no statistical difference. Degree of wall inflammation demonstrated stronger association with FHSQ score (r = −0.454, p < 0.001) than artery diameter (r = −0.361, p < 0.001) and lumen-to-artery diameter ratio (r = 0.404, p < 0.001), while FHSQ score did not relate to lumen diameter (p = 0.798) nor peak systolic velocity (p = 0.258). ConclusionWe identified specific vascular ultrasound parameters were associated with foot symptoms among people with RA. This non-invasive imaging technique may be a viable method to monitor foot health and disease management.

Nutritional interventions as modulators of the disease activity for idiopathic inflammatory myopathies: a scoping review.

Idiopathic inflammatory myopathies (IIMs) are chronic, autoimmune connective tissue diseases associated with significant morbidity and disability. Nutrients can activate the immune system and contribute to chronic low-grade inflammation (LGI). Chronic muscle inflammation leads to imbalanced pro-inflammatory and anti-inflammatory cytokines, causing inadequate nutrition, weight loss and muscle weakness during a negative cycle. Owing to its potential to modulate LGI in various diseases, the Mediterranean diet (Med Diet) has been extensively studied. This scoping review explores the nutritional implications and recommendations of the Med Diet as a treatment for immune-mediated diseases, focusing on the gaps in IIM nutritional interventions. A comprehensive literature search of the MEDLINE and EBSCO databases between September 2018 and December 2022 was performed. We identified that the Med Diet and its specific components, such as omega-3 (nω3) fatty acids, vitamin D and antioxidants, play a role in the dietary treatment of connective tissue-related autoimmune diseases. Nutritional interventions have demonstrated potential for modulating disease activity and warrant further exploration of IIMs through experimental studies. This review introduces a dietary therapeutic approach using the Med Diet and related compounds to regulate chronic inflammatory processes in IIMs. However, further clinical studies are required to evaluate the efficacy of the Med Diet in patients with IIMs. Emphasising a clinical-nutritional approach, this study encourages future research on the anti-inflammatory effects of the Med Diet on IIMs. This review highlights potential insights for managing and treating these conditions using a holistic approach.

Therapeutic management of fibrosis in systemic sclerosis patients - an analysis from the Swiss EUSTAR cohort.

Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations. Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of <70%. A total of 590 patients with systemic sclerosis fulfilled the inclusion criteria. In this cohort, 421 (71.4%) had mRSS >0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation. Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported.

Rapid diagnosis of systemic lupus erythematosus by Raman spectroscopy combined with spiking neural network

Multiple organs are affected by the autoimmune inflammatory connective tissue disease known as systemic lupus erythematosus (SLE). If not diagnosed and treated in a timely manner, it can lead to nephritis and damage to the blood system in severe cases, resulting in the patient's death. Therefore, correct and timely diagnosis and treatment are essential for patients. In this study, a framework based on neural network algorithm and Raman spectroscopy technique was established to diagnose SLE patients. Firstly, we pre-processed the obtained Raman data by three methods: baseline correction, smoothing processing and normalization methods, before using it as input for the model, and then ANN, ResNet and SNN classification models were established. The respective classification accuracies for SLE patients were 89.61%, 85.71%, and 95.65% for the three models, with corresponding AUC values of 0.8772, 0.8100, and 0.9555. The results of the experimental indicate that SNN possesses a good classification effect, and the number of model parameters is only 525,826, which is 414,221 less than that of ResNet model. Since the network only uses 0 and 1 to transmit information, and only has basic operations such as summation, compared with the second-generation artificial neural network, which simplifies the product operation of floating point numbers into multiple addition operations, the network has low energy consumption and is suitable for embedding portable Raman spectrometer for clinical diagnosis. This research highlights the significant potential for quick and precise SLE patient discrimination offered by Raman spectroscopy in conjunction with spiking neural networks.

Exosomal miR‐126‐3p: Potential protection against vascular damage by regulating the SLC7A5/mTOR Signalling pathway in human umbilical vein endothelial cells

AbstractSystemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Vascular damage is one of the important features of SSc, which affects the progression and prognosis of the disease. MiR‐126‐3p is an important microRNA (miRNA) that regulates vascular structure and function, which can be transported through exosomes. However, the role of miR‐126‐3p in vascular damage in SSc is still unclear. Therefore, we focused on the connection between miR‐126‐3p and vascular damage in SSc, as well as investigated the potential role of miR‐126‐3p in vascular damage in SSc. First, this study successfully extracted extracellular vesicles from clinical plasma samples and characterized the exosomes within them. Then, we predicted and screened the target pathway mammalian/mechanistic target of rapamycin (mTOR) and the target gene SLC7A5 of miR‐126‐3p through online databases. Next, we constructed SSc mice for in vivo studies. The results showed that the expression of miR‐126‐3p was decreased in the plasma exosomes, while the SLC7A5 expression, autophagy, and lipid peroxidation were increased in the aorta. Luciferase reporter gene assays demonstrated that miR‐126‐3p can bind to SLC7A5, resulting in a decrease in its expression. In vitro experiments have shown that exosomal miR‐126‐3p can be internalized by human umbilical vein endothelial cells (HUVECs). The miR‐126‐3p group exhibited enhanced cell viability and tube formation ability, along with increased expression of the vascular formation marker CD31. Additionally, miR‐126‐3p downregulated the protein expression of SLC7A5 and LC3 in HUVECs, while upregulating the protein expression of mTOR, P62, PPARγ, and CPT‐1. However, the effects of miR‐126‐3p on HUVECs were counteracted by mTOR inhibitors and enhanced by mTOR activators. The results indicated that exosomal miR‐126‐3p has the potential to protect against vascular injury in SSc by regulating the SLC7A5/mTOR signalling pathway in HUVECs.

Right ventricular-pulmonary arterial coupling ratio derived from 3-dimensional echocardiography predicts outcomes in systemic lupus erythematosus-associated pulmonary arterial hypertension patients.

Systemic lupus erythematosus (SLE) is a complex autoimmune connective tissue disease (CTD) that is an important cause of devastating pulmonary arterial hypertension (PAH), and persistent progression of PAH can lead to right heart failure, predicting a poor prognosis for SLE patients. Right ventricular-pulmonary arterial (RV-PA) coupling with echocardiography has been demonstrated to be a noninvasive alternative method for evaluating PAH patients' predictive outcomes. Whether the ratio of right ventricular stroke volume (RVSV) to right ventricular end-systolic volume (RVESV) measured by three-dimensional echocardiography (3DE) is a new index of RV-PA coupling has not been discussed as a new predictor for the clinical outcome of systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). From June 2019 to February 2023, 46 consecutive patients with SLE-PAH were enrolled prospectively, and their clinical data and echocardiographs were studied and analyzed. The control group consisted of 30 healthy subjects matched for age, sex, and body surface area (BSA). The main endpoints of this study were a composite of all-cause mortality and adverse clinical events. Baseline clinical characteristics and echocardiographic assessments were analyzed. During a median of 24months (IQR 18-31), 16 of 46 SLE-PAH patients (34.7%) experienced endpoint-related events. At baseline, patients who experienced mortality or adverse events had a worse WHO functional class (WHO FC) and lower anti-double-stranded DNA (dsDNA) antibody levels. The right ventricular (RV) systolic dysfunction in SLE-PAH subjects was significantly worse than that in the healthy control group, especially in SLE-PAH patients in the endpoint event group. Compared to controls, patients with SLE-PAH had a lower RVSV/RVESV ratio. In the group comparison, patients who had experienced an endpoint event had a sequentially worse ratio (1.86 (1.65-2.3) versus 1.30 (1.09-1.46) versus 0.64 (0.59-0.67), p < .001). There were statistically significant associations between the RVSV/RVESV ratio to routine RV systolic function and clinical parameters. The RVSV/RVESV ratio was negatively correlated with the WHO FC (r = -0.621, p < .001) and positively correlated with the anti-dsDNA level. The ROC curve showed that the optimal cutoff for RVSV/RVESV < 0.712 determined a higher risk of poor prognosis. Kaplan‒Meier survival curves showed that an RVSV/RVESV ratio >0.712 was associated with more favorable long-term outcomes. The 3DE-derived SV/ESV ratio as a noninvasive alternative surrogate of RV-PA coupling was an eximious indicator for identifying endpoint events in SLE-PAH patients and can provide a diagnostic basis for clinical intervention.

Systemic Sclerosis in Males-Deciphering the Enigma of Erasmus Syndrome.

Systemic sclerosis is an autoimmune connective tissue disease characterized by fibrosis in skin and internal organs. Chronic exposure to silica may not only lead to silicosis of lungs but also systemic sclerosis. Systemic sclerosis is relatively commoner in females; however, occupational exposure to silica in males makes them vulnerable to silica--associated systemic sclerosis (Erasmus syndrome). To describe the clinico-epidemiological aspects of systemic sclerosis in males in a retrospective cohort study. The data were analysed retrospectively for demographic profile and clinical characteristics including examination findings, laboratory investigations, and treatments of all male patients diagnosed with systemic sclerosis with or without silica exposure, managed from January 2018 to December 2021. Eight out of twelve patients were having silica exposure in the form of stone cutting, cement exposure, and working with concrete. The average age was 55 ± 10.72 years with average smoking exposure of around 24.4 ± 12.8 pack years. Skin thickening was reported by all patients with an average modified Rodnan score of 18.33/51 in diffuse and 7/51 in limited cutaneous systemic sclerosis. Raynaud's phenomenon and sclerodactyly were universal findings, while 9 (75%) patients had digital pitted scars. Antinuclear antibodies were present in all patients and specific antibodies substantiated the clinical assessment in almost all patients. Interstitial lung disease was the most common systemic finding present in 11 (91%) patients and tuberculosis was diagnosed in 2 (25%) cases with silica exposure. Gastrointestinal and cardiac system involvement was seen in 5 (41.6%) and 4 (33.3%) patients, respectively. Systemic sclerosis in males against the gender predilection indicates the role of occupational exposure. Silicosis and systemic sclerosis synergistically add to lung damage, and at the same time, these patients are more prone to infections like tuberculosis.

Manifestations of systemic connective tissue diseases on the oral mucosa: a literature review

Annotation. Despite the modern high level of medical care, autoimmune connective tissue diseases cause a lot of questions among scientists and are a significant problem for society. At the same time, in the scientific works available today, little attention is paid to the manifestations of connective tissue diseases in the oral cavity and modern diagnostics of the main types of dental pathology in such patients, which would have great scientific and practical importance. Therefore, the purpose of the review article was to perform an analysis of the scientific literature regarding orofacial manifestations of autoimmune connective tissue diseases. When using the following databases: PubMed, Google Scholar, Scopus, Web of Science and various combinations of keywords and subject headings of MESH such as “oral manifestations”, “oral mucosal lesions”, “autoimmune diseases”, “rheumatic diseases”, “connective tissue diseases”, “systemic lupus erythematosus”, “rheumatoid arthritis”, “systemic sclerosis”, “Sjögren’s syndrome”, “dermatomyositis”, 40 articles were chosen, which corresponded to the purpose of the study. The search results indicate that there is a direct correlation between the duration of the main disease and the severity of oral symptoms. Pronounced hyposalivation and dryness of oral mucosa are the most similar common signs of autoimmune diseases, which contributes to functional disorders and diseases of oral cavity. Oral manifestations are quite often a side effect of the treatment of connective tissue diseases. The pathology of oral mucosa in autoimmune diseases remains not well-understood, so makes it difficult to clarify its pathogenesis in detail, that would allow for the development of justified measures of prevention and treatment.