Esofagitis disecante supeEsofagitis disecante superficial: dos casos de una misma entidad poco frecuente / Esophagitis dissecans superficialis: two cases of the same rare entity

La esofagitis disecante superficial (EDS) es una entidad infrecuente que se caracteriza endoscópicamente por el desprendimiento de las capas superficiales del epitelio esofágico e, histológicamente, por el aspecto bitonal del epitelio escamoso esofágico secundario a la necrosis de los estratos más superficiales. La etiología es desconocida, aunque se ha asociado con la ingesta de determinados fármacos, enfermedades autoinmunes, estasis esofágica y procedimientos endoscópicos. Presentamos dos casos: uno de ellos acontece en una mujer tras un episodio de disfagia abrupta y el segundo en un varón con comorbilidades y clínica de dolor epigástrico. La EDS es una patología que hay que considerar en su adecuado contexto clínico y endoscópico, ya que su curso es autolimitado en comparación con otras entidades de evolución tórpida o que precisan un tratamiento específico. (AU)

Esophagitis dissecans superficialis (EDS) is a rare disease characterized by sloughing of the superficial esophageal mucosa and, histologically, by the bitonal appearance of the squamous epithelium secondary to necrosis of the most superficial layers. Etiology is uncertain, however, it has been associated with some medications, autoimmune diseases, esophageal stasis and endoscopic procedures. Here, two cases are presented, one of them which appeared in a woman after an episode of dysphagia and another one which occurred to a man with comorbidities and epigastric pain. This entity should be considered due to its self-limiting clinical course, compared to other entities with a more torpid evolution or that require more specific treatment. (AU)

A new vision of the efficacy of both CAR-NK and CAR-T cells in treating cancers and autoimmune diseases.

Chimeric Antigen Receptor (CAR) based therapies are becoming increasingly important in treating patients. CAR-T cells have been shown to be highly effective in the treatment of hematological malignancies. However, harmful therapeutic barriers have been identified, such as the potential for graft-versus-host disease (GVHD), neurotoxicity, and cytokine release syndrome (CRS). As a result, CAR NK-cell therapy is expected to be a new therapeutic option. NK cells act as cytotoxic lymphocytes, supporting the innate immune response against autoimmune diseases and cancer cells by precisely detecting and eliminating malignant cells. Genetic modification of these cells provides a dual approach to the treatment of AD and cancer. It can be used through both CAR-independent and CAR-dependent mechanisms. The use of CAR-based cell therapies has been successful in treating cancer patients, leading to further investigation of this innovative treatment for alternative diseases, including AD. The complementary roles of CAR T and CAR NK cells have stimulated exploration in this area. Our study examines the latest research on the therapeutic effectiveness of these cells in treating both cancer and ADs.

Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study.

OBJECTIVES: To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. METHODS: Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. RESULTS: We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. CONCLUSIONS: Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

[Anti-MOG associated disease]. / Maladie du spectre des anticorps anti-MOG.

Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease (MOGAD) is an autoimmune disease responsible for demyelination of the central nervous system that can occur in adults or children. Overlapping phenotypes between MOGAD, multiple sclerosis (MS) and neuromyelitis optica spectrum disease (NMOSD) have been described. The diagnostic criteria for MOGAD were proposed by a panel of international experts and published in 2023. Defining clinical, biological and imaging characteristics specific to this entity helps to improve diagnostic specificity. In this article, we present the clinical characteristics suggestive of MOGAD and discuss the importance of the antibody detection method and therapeutic management.

La maladie du spectre des anticorps anti-MOG (glycoprotéine de myéline oligodendrocytaire) (myelin oligodendrocyte glycoprotein antibody-associated disease, MOGAD) est une maladie autoimmune responsable d'une démyélinisation du système nerveux central pouvant survenir chez les adultes ou les enfants. Des phénotypes de chevauchement entre MOGAD, sclérose en plaques et maladie du spectre de la neuromyélite optique ont été décrits. Les critères diagnostiques de MOGAD ont été proposés par un panel d'experts internationaux et publiés en 2023. Ils permettent de définir des caractéristiques cliniques, biologiques et d'imagerie propres à cette entité, afin d'améliorer la spécificité diagnostique. Nous présentons dans cet article les caractéristiques cliniques en faveur de MOGAD, discutons de l'importance de la méthode de détection des anticorps et terminons par une mise au point sur la prise en charge thérapeutique.

Anti-synthase syndrome associated with SARS-Cov-2 infection.

BACKGROUND: Anti-synthetase syndrome (AS) is a rare autoimmune idiopathic inflammatory myopathy (IIM) with diverse manifestations, including arthritis, interstitial lung disease (ILD), Raynaud's phenomenon, unexplained persistent fever, and mechanic's hands. CASE PRESENTATION: We present the case of a 72-year-old woman, previously healthy, who was admitted to our hospital for treatment of cough and rapid breathing. The patient had elevated white blood cells and C-reactive protein, and tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). She was initially diagnosed with community-acquired pneumonia and received tamoxifen for anti-infection treatment, but her dystonia worsened. She eventually required non-invasive ventilator support, tested positive for SARS-Cov-2 again, and started antiviral therapy, corticosteroids to reduce alveolar effusion, anticoagulation, and other treatments. However, her condition continued to deteriorate, with the lowest oxygenation index reaching only 80mmHg. Ultimately, she underwent tracheal intubation and mechanical ventilation. Chest CT revealed rapid progressive interstitial changes in her lungs, and her hands showed noticeable fraternization changes. At this point, we suspected that the novel coronavirus infection might be associated with autoimmune diseases. The patient's autoimmune antibody spectrum showed positive results for anti-recombinant RO-52 antibody and myositis-specific antibody anti-alanyl tRNA synthetase (anti-PL-12). The patient was treated with dexamethasone sodium phosphate for anti-inflammatory and anti-fibrotic effects. After successful extubation, the patient was discharged with only oral prednisone tablets at a dose of 30 mg. CONCLUSIONS: This case presents an early diagnosis and successful treatment of anti-synthetase syndrome combined with SARS-Cov-2 infection, emphasizing the importance of comprehensive physical examination. Additionally, it highlights the rapid progression of interstitial lung disease under SARS-Cov-2 infection, which is often difficult to distinguish on imaging. In cases where treatment for SARS-Cov-2 infection is ineffective, early screening for autoimmune diseases is recommended. As there is currently no standardized method for treating AS-ILD, the successful treatment of this case provides a reference for clinical research on anti-synthetase syndrome in the later stage.

Macrophage polarization: an important role in inflammatory diseases.

Macrophages are crucial cells in the human body's innate immunity and are engaged in a variety of non-inflammatory reactions. Macrophages can develop into two kinds when stimulated by distinct internal environments: pro-inflammatory M1-like macrophages and anti-inflammatory M2-type macrophages. During inflammation, the two kinds of macrophages are activated alternatively, and maintaining a reasonably steady ratio is critical for maintaining homeostasis in vivo. M1 macrophages can induce inflammation, but M2 macrophages suppress it. The imbalance between the two kinds of macrophages will have a significant impact on the illness process. As a result, there are an increasing number of research being conducted on relieving or curing illnesses by altering the amount of macrophages. This review summarizes the role of macrophage polarization in various inflammatory diseases, including autoimmune diseases (RA, EAE, MS, AIH, IBD, CD), allergic diseases (allergic rhinitis, allergic dermatitis, allergic asthma), atherosclerosis, obesity and type 2 diabetes, metabolic homeostasis, and the compounds or drugs that have been discovered or applied to the treatment of these diseases by targeting macrophage polarization.

Autoimmune diseases and their genetic link to bronchiectasis: insights from a genetic correlation and Mendelian randomization study.

Background: Previous studies have demonstrated that autoimmune diseases are closely associated with bronchiectasis (BE). However, the causal effects between autoimmune diseases and BE remain elusive. Methods: All summary-level data were obtained from large-scale Genome-Wide Association Studies (GWAS). The univariate Mendelian randomization (UVMR) was utilized to investigate the genetic causal correlation (rg) of 12 autoimmune diseases and bronchiectasis, The Multivariable Mendelian Randomization (MVMR) method was used to explore the effects of the confounding factors. Further investigation was conducted to identify potential intermediate factors using mediation analysis. Finally, the linkage disequilibrium score regression (LDSC) method was used to identify genetic correlations among complex traits. A series of sensitivity analyses was performed to validate the robustness of the results. Results: The LDSC analysis revealed significant genetic correlations between BE and Crohn's disease (CD) (rg = 0.220, P = 0.037), rheumatoid arthritis (RA) (rg = 0.210, P = 0.021), and ulcerative colitis (UC) (rg = 0.247, P = 0.023). However, no genetic correlation was found with other autoimmune diseases (P > 0.05). The results of the primary IVW analysis suggested that for every SD increase in RA, there was a 10.3% increase in the incidence of BE (odds ratio [OR] = 1.103, 95% confidence interval [CI] 1.055-1.154, P = 1.75×10-5, FDR = 5.25×10-5). Furthermore, for every standard deviation (SD) increase in celiac disease (CeD), the incidence of BE reduced by 5.1% (OR = 0.949, 95% CI 0.902-0.999, P = 0.044, FDR = 0.044). We also observed suggestive evidence corresponding to a 3% increase in BE incidence with T1DM (OR = 1.033, 95% CI 1.001-1.066, P = 0.042, FDR = 0.063). Furthermore, MVMR analysis showed that RA was an independent risk factor for BE, whereas mediator MR analysis did not identify any mediating factors. The sensitivity analyses corroborated the robustness of these findings. Conclusion: LDSC analysis revealed significant genetic correlations between several autoimmune diseases and BE, and further MVMR analysis showed that RA is an independent risk factor for BE.

NLRP inflammasomes in health and disease.

NLRP inflammasomes are a group of cytosolic multiprotein oligomer pattern recognition receptors (PRRs) involved in the recognition of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) produced by infected cells. They regulate innate immunity by triggering a protective inflammatory response. However, despite their protective role, aberrant NLPR inflammasome activation and gain-of-function mutations in NLRP sensor proteins are involved in occurrence and enhancement of non-communicating autoimmune, auto-inflammatory, and neurodegenerative diseases. In the last few years, significant advances have been achieved in the understanding of the NLRP inflammasome physiological functions and their molecular mechanisms of activation, as well as therapeutics that target NLRP inflammasome activity in inflammatory diseases. Here, we provide the latest research progress on NLRP inflammasomes, including NLRP1, CARD8, NLRP3, NLRP6, NLRP7, NLRP2, NLRP9, NLRP10, and NLRP12 regarding their structural and assembling features, signaling transduction and molecular activation mechanisms. Importantly, we highlight the mechanisms associated with NLRP inflammasome dysregulation involved in numerous human auto-inflammatory, autoimmune, and neurodegenerative diseases. Overall, we summarize the latest discoveries in NLRP biology, their forming inflammasomes, and their role in health and diseases, and provide therapeutic strategies and perspectives for future studies about NLRP inflammasomes.

Serum vitamins and homocysteine levels in autoimmune liver disease: A systematic review and meta-analysis.

OBJECTIVE: Vitamins and homocysteine (Hcy) are involved in liver metabolism and related to the pathogenesis of autoimmune liver disease (AILD), but consensus is lacking. This study aims to systematically summarize relevant evidence to clarify the association of serum vitamins and Hcy levels with AILD. METHODS: The English and Chinese literature was searched until August 29, 2023. Studies were included if they were observational studies of investigating serum vitamins and Hcy levels in patients with AILD and their healthy comparisons. Quality assessment was performed by using the Newcastle-Ottawa Scale, and a meta-analysis was conducted using ReviewManager 5.3. The protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42023455367. RESULTS: A total of 25 case-control studies comprising 3487 patients (1673 patients and 1814 healthy controls) were included for analysis. There were 548 autoimmune hepatitis (AIH) cases, 1106 primary biliary cholangitis (PBC) cases, and 19 primary sclerosing cholangitis (PSC) cases. We found that serum A and E were decreased in both AIH and PBC/PSC; but vitamin C was reduced only in patients with PBC, not AIH. In addition, decreased content of 25(OH)D3 was found in both AIH and PBC. However, levels of 25(OH)D did not differ between the patients and controls, and were independent of disease types and the country. Only one study that met the inclusion criteria reported vitamin B6, B9, B12, and Hcy changes, and found that vitamin B6 and B9 were significantly decreased in patients with PBC, while serum vitamin B12 and Hcy levels were significantly elevated in them. One eligible study each confirmed a reduction in plasma vitamin K1 and 1,25(OH)2D3 in patients with PBC. CONCLUSION: Most vitamins are deficient in AILD, so appropriate vitamin supplementation should be necessary. Further studies with larger sample sizes are needed to validate these findings.

Immune Homeostasis: A Novel Example of Teamwork.

All living organisms must maintain homeostasis to survive, reproduce, and pass their traits on to the next generation. If homeostasis is not maintained, it can result in various diseases and ultimately lead to death. Physiologists have coined the term "homeostasis" to describe this process. With the emergence of immunology as a separate branch of medicine, the concept of immune homeostasis has been introduced. Maintaining immune homeostasis is crucial to support overall homeostasis through different immunological and non-immunological routes. Any changes in the immune system can lead to chronic inflammatory or autoimmune diseases, immunodeficiency diseases, frequent infections, and cancers. Ongoing scientific advances are exploring new avenues in immunology and immune homeostasis maintenance. This chapter introduces the concept of immune homeostasis and its maintenance through different mechanisms.

Isolation and Single-Cell Transcriptomic Analysis of Murine Regulatory B Cells.

Regulatory B (Breg) cells have been demonstrated to play an important role in the inhibition of a wide range of immunological responses, and they are absent or malfunction in autoimmune diseases like lupus. Breg cells can control immunological responses and keep the immune system in a balanced state by releasing immunosuppressive cytokines such as transforming growth factor-beta (TGF-ß) and interleukin-10 (IL-10), which in turn promote regulatory T (Treg) cells and reduce effector T cell responses. Breg cells have also been linked to the modulation of cancer immunity. Due to their immunosuppressive role, in the context of cancer, Breg cells aid in tumor immune evasion and promote tumor progression. Nonetheless, it has been established that Breg cells are involved in both cancer immunity and autoimmunity, and their characterizations beyond surface markers, for example, on the transcriptomic level, are essential for our understanding of Breg biology in health and disease. In this chapter, using lupus-prone MRL/lpr mice, we describe a Breg cell isolation protocol for the purpose of single-cell RNA sequencing analysis.

Identifying antinuclear antibody positive individuals at risk for developing systemic autoimmune disease: development and validation of a real-time risk model.

Objective: Positive antinuclear antibodies (ANAs) cause diagnostic dilemmas for clinicians. Currently, no tools exist to help clinicians interpret the significance of a positive ANA in individuals without diagnosed autoimmune diseases. We developed and validated a risk model to predict risk of developing autoimmune disease in positive ANA individuals. Methods: Using a de-identified electronic health record (EHR), we randomly chart reviewed 2,000 positive ANA individuals to determine if a systemic autoimmune disease was diagnosed by a rheumatologist. A priori, we considered demographics, billing codes for autoimmune disease-related symptoms, and laboratory values as variables for the risk model. We performed logistic regression and machine learning models using training and validation samples. Results: We assembled training (n = 1030) and validation (n = 449) sets. Positive ANA individuals who were younger, female, had a higher titer ANA, higher platelet count, disease-specific autoantibodies, and more billing codes related to symptoms of autoimmune diseases were all more likely to develop autoimmune diseases. The most important variables included having a disease-specific autoantibody, number of billing codes for autoimmune disease-related symptoms, and platelet count. In the logistic regression model, AUC was 0.83 (95% CI 0.79-0.86) in the training set and 0.75 (95% CI 0.68-0.81) in the validation set. Conclusion: We developed and validated a risk model that predicts risk for developing systemic autoimmune diseases and can be deployed easily within the EHR. The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals.

Understanding patient perspectives on vaccine decision making in adults with autoimmune bullous diseases: a qualitative study.

Patients with autoimmune bullous diseases are at an increased risk of infection, both from the underlying skin disease and from immunosuppressive treatments. Limited information is available on vaccine beliefs and behaviors in dermatology patients and adults with autoimmune bullous diseases in particular. To understand vaccine decision making, identify perceived risks and benefits of vaccinations, and discuss individual experiences in patients with autoimmune bullous diseases in the United States. A qualitative study was performed utilizing semi-structured interviews, and analysis was conducted on NVivo. Patterns were identified in the coded data, and representative quotations were recorded for each major theme. Interviews were conducted between February 15, 2022 and September 15, 2022. Twenty patients with a diagnosis of bullous pemphigoid, mucous membrane pemphigoid, pemphigus vulgaris, or pemphigus foliaceous were interviewed. Of the 20 participants, 14 (70%) were female, with a mean (SD, range) age of 64.8 (13.2, 34-83) years. Key themes that emerged from qualitative analysis of the interviews included patient concerns regarding their increased susceptibility to infection, potential exacerbation of skin disease following vaccination, and the effect of immunosuppressive medications on humoral response to vaccines. Lack of appointment availability, difficulty accessing vaccines, and cost were commonly identified barriers to vaccination. These findings provide valuable knowledge for dermatologists in regard to providing counseling specific to patient concerns and to improve communication surrounding vaccination in the dermatology setting.

Programmed cell death in autoimmune diseases: ferroptosis.

Ferroptosis is an iron dependent cell death driven by lipid peroxidation. Over the past decade, increasing evidence has confirmed that ferroptosis plays an irreplaceable role in the occurrence and development of many diseases, including various cancers, neurodegenerative diseases, cardiovascular diseases and autoimmune diseases. Autoimmune disease is an inflammatory disease characterized by the breakdown of immune tolerance. Nowadays, accumulating evidence indicates that ferroptosis is closely related to the pathogenesis of autoimmune diseases. Therefore, this review briefly introduced the mechanism of ferroptosis, and focused on the related research of ferroptosis in multiple autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), ankylosing spondylitis (AS). In addition, we also presented the idea of targeting ferroptosis as a potential therapeutic target for patients with autoimmune diseases, which may provide a direction for the development of new therapeutic strategies.

[Restorative capability of traditional Chinese medicine in autoimmune diseases of nervous system: a literature review]. / Vosstanovitel'nyi potentsial traditsionnoi kitaiskoi meditsiny pri autoimmunnykh zabolevaniyakh nervnoi sistemy: obzor literatury.

Autoimmune diseases of the nervous system are characterized by the formation of pronounced neurological deficiency and often lead to disability. Complementary medicine as an adjuvant or preventive therapy of various diseases, including autoimmune ones, is increasingly attracting the attention of doctors and researchers. Traditional Chinese medicine (TCM) has a complex of treatment methods, including acupuncture, phytotherapy, nutrition, physical exercises and other methods that are often used in common with the recognized approaches of the official medical science. The article describes the TCM methods application in autoimmune diseases of nervous system, presents the practical experience of using acupuncture, phytotherapy, diet, physical exercises. It was concluded that TCM is important and frequently underestimated health care resource, especially in prevention and treatment of autoimmune diseases of nervous system.

Novel and potential future therapeutic options in systemic autoimmune diseases.

Autoimmune inflammation is caused by the loss of tolerance to specific self-antigens and can result in organ-specific or systemic disorders. Systemic autoimmune diseases affect a significant portion of the population with an increasing rate of incidence, which means that is essential to have effective therapies to control these chronic disorders. Unfortunately, several patients with systemic autoimmune diseases do not respond at all or just partially respond to available conventional synthetic disease-modifying antirheumatic drugs and targeted therapies. However, during the past few years, some new medications have been approved and can be used in real-life clinical settings. Meanwhile, several new candidates appeared and can offer promising novel treatment options in the future. Here, we summarize the newly available medications and the most encouraging drug candidates in the treatment of systemic lupus erythematosus, rheumatoid arthritis, Sjögren's disease, systemic sclerosis, systemic vasculitis, and autoimmune myositis.

A bibliometric analysis of miRNAs in rheumatoid arthritis from 2001 to 2022: Research hotspots and trends.

BACKGROUND: MicroRNAs (miRNAs) are widely recognized in the pathogenesis of autoimmune disease. As a key regulatory factor, miRNAs have introduced new biomarkers for the early diagnosis of rheumatoid arthritis (RA) and provided a favorable research direction for the development of novel therapeutic targets. This study aimed to explore the hotspots of miRNA research related to RA published from different countries, organizations, and authors. METHODS: From 2001 to 2022, publications on miRNA related to RA were identified in the Web of Science database. The total and annual number of publishments, citations, impact factor, H-index, productive authors, and involved journals were collected for quantitative and qualitative comparisons. RESULTS: A total of 29 countries/regions in the world have participated in the research of miRNAs and RA over the past two decades, and China (760, 53.18%) and the United States (233, 16.31%) account for the majority of the total publications. China dominated in total citation (17881) and H-index (62). A total of 507 academic journals have published articles in related fields, and Frontiers in Immunology published the most (53, 3.71%). Chih-hsin Tang of the China Medical University has published the most papers (16, 1.2%). Stanczyk (2008) published the most cited article Altered expression of miRNAs in synovial fibroblasts and synovial tissue in rheumatoid arthritis in Arthritis and Rheumatism, with 660 citations. Inflammation is the high-frequency keyword outside of RA and miRNAs, and related researches have mainly focused on miR-146a and miR-155. CONCLUSIONS: In the past two decades, extensive and continuous research has been conducted to investigate the role of miRNAs in RA, and miRNAs are widely recognized in the pathogenesis of RA. Related research has mainly focused on miR-146a and miR-155 that have shown promising results as key factors in RA experimental models. Focusing on clinical applications and translational research may be the future research direction and hotspot based on molecular biology basic research and mechanism exploration.