Pub Date : 2025-01-31DOI: 10.1016/j.autrev.2024.103722
Rémi Philip , Inès Elhani , Sophie Gallou , Hubert De Boysson , Nicolas Martin Silva , Sophie Georgin-Lavialle , Samuel Deshayes , Achille Aouba
Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathophysiology remains incompletely understood, involving genetic and epigenetic factors. However, an increasing small subset of patients present with monogenic lupus, providing insight into the pathogenesis of the disease. This systematic review focuses on SLE associated with A20 haploinsufficiency (HA20), a monogenic disorder associated with tumor necrosis factor alpha-induced protein 3 gene (TNFAIP3) variants. Besides the mainly auto-inflammatory phenotypic expression of HA20 mimicking Behçet's disease spectrum, some of its clinical and biological manifestations are part of the spectrum of autoimmune diseases, including glomerulonephritis as well as the frequent presence of antinuclear antibodies, sometimes with anti-DNA specificity. Among all the 191 HA20 patients reported in the literature, we identified 16 patients (8.4 %) with a compatible diagnosis of SLE. When estimable, the SLICC 2012 and EULAR/ACR 2019 classification criteria were positive for 92.9 % of them. A majority had multi-system involvement, mainly cutaneous (81.3 %), musculoskeletal (56.3 %), and/or renal (56.3 %) manifestations. They also seemed to exhibit differences compared to other SLE patients: higher prevalence of fever, chronic cutaneous lupus erythematosus, oral and genital ulcers, neuropsychiatric manifestations, autoimmune cytopenia, and elevated biologic inflammatory markers. This review highlights the necessity of considering TNFAIP3 variants in SLE patients with early-onset disease, familial history, and/or specific clinical manifestations suggestive of autoinflammatory diseases. Recognizing HA20-SLE patients may improve our understanding of SLE pathogenesis and lead to better therapeutic strategies for these patients.
{"title":"A20 haploinsufficiency diagnosis beyond systemic lupus erythematosus: A systematic review of the literature","authors":"Rémi Philip , Inès Elhani , Sophie Gallou , Hubert De Boysson , Nicolas Martin Silva , Sophie Georgin-Lavialle , Samuel Deshayes , Achille Aouba","doi":"10.1016/j.autrev.2024.103722","DOIUrl":"10.1016/j.autrev.2024.103722","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathophysiology remains incompletely understood, involving genetic and epigenetic factors. However, an increasing small subset of patients present with monogenic lupus, providing insight into the pathogenesis of the disease. This systematic review focuses on SLE associated with A20 haploinsufficiency (HA20), a monogenic disorder associated with tumor necrosis factor alpha-induced protein 3 gene (<em>TNFAIP3)</em> variants. Besides the mainly auto-inflammatory phenotypic expression of HA20 mimicking Behçet's disease spectrum, some of its clinical and biological manifestations are part of the spectrum of autoimmune diseases, including glomerulonephritis as well as the frequent presence of antinuclear antibodies, sometimes with anti-DNA specificity. Among all the 191 HA20 patients reported in the literature, we identified 16 patients (8.4 %) with a compatible diagnosis of SLE. When estimable, the SLICC 2012 and EULAR/ACR 2019 classification criteria were positive for 92.9 % of them. A majority had multi-system involvement, mainly cutaneous (81.3 %), musculoskeletal (56.3 %), and/or renal (56.3 %) manifestations. They also seemed to exhibit differences compared to other SLE patients: higher prevalence of fever, chronic cutaneous lupus erythematosus, oral and genital ulcers, neuropsychiatric manifestations, autoimmune cytopenia, and elevated biologic inflammatory markers. This review highlights the necessity of considering <em>TNFAIP3</em> variants in SLE patients with early-onset disease, familial history, and/or specific clinical manifestations suggestive of autoinflammatory diseases. Recognizing HA20-SLE patients may improve our understanding of SLE pathogenesis and lead to better therapeutic strategies for these patients.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 2","pages":"Article 103722"},"PeriodicalIF":9.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IgG4-related disease (IgG4-RD) is a chronic inflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells, leading to fibrosis and organ dysfunction. While primarily affecting the pancreas, bile ducts, and salivary glands, IgG4-RD can also involve the gastrointestinal tract, raising questions about its relationship with inflammatory bowel disease (IBD).
Recent studies suggest that patients with IBD may exhibit histological and serological features consistent with IgG4-RD, such as a dense lymphoplasmacytic infiltration, a storiform-type of fibrosis and a prominent IgG4 immune response. This overlap represents a diagnostic challenge, as differentiating between primary IBD and IgG4-RD involving the gut is crucial for appropriate treatment.
Further research is essential to delineate the prevalence of tissue and serum IgG4 expression in patients with IBD. This approach could classify subtypes of IBD, enabling advancements in non-invasive diagnosis and monitoring as well as personalized therapies. The purpose of this review is to summarize the available evidence regarding intestinal involvement in IgG4-RD and the role of both serum and tissue IgG4 in inflammatory bowel diseases IBD.
{"title":"IgG4 in the gut: Gastrointestinal IgG4-related disease or a new subtype of inflammatory bowel disease","authors":"Sarah Bencardino , Cosimo Simone Matichecchia , Jacopo Fanizza , Laurent Peyrin-Biroulet , Emanuel Della-Torre , Silvio Danese , Ferdinando D’Amico","doi":"10.1016/j.autrev.2024.103720","DOIUrl":"10.1016/j.autrev.2024.103720","url":null,"abstract":"<div><div>IgG4-related disease (IgG4-RD) is a chronic inflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells, leading to fibrosis and organ dysfunction. While primarily affecting the pancreas, bile ducts, and salivary glands, IgG4-RD can also involve the gastrointestinal tract, raising questions about its relationship with inflammatory bowel disease (IBD).</div><div>Recent studies suggest that patients with IBD may exhibit histological and serological features consistent with IgG4-RD, such as a dense lymphoplasmacytic infiltration, a storiform-type of fibrosis and a prominent IgG4 immune response. This overlap represents a diagnostic challenge, as differentiating between primary IBD and IgG4-RD involving the gut is crucial for appropriate treatment.</div><div>Further research is essential to delineate the prevalence of tissue and serum IgG4 expression in patients with IBD. This approach could classify subtypes of IBD, enabling advancements in non-invasive diagnosis and monitoring as well as personalized therapies. The purpose of this review is to summarize the available evidence regarding intestinal involvement in IgG4-RD and the role of both serum and tissue IgG4 in inflammatory bowel diseases IBD.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 2","pages":"Article 103720"},"PeriodicalIF":9.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.autrev.2024.103721
Ze Yang , Yanzuo Wu , Shuo Huang , Jie Bao , Li Xu , Yongsheng Fan
Background
Systemic lupus erythematosus (SLE) frequently manifests with thrombocytopenia (TP), a hematologic complication that heightens the risk of severe outcomes and increases mortality. This meta-analysis aims to evaluate the potential risk factors associated with TP in SLE patients, providing insights into the demographic features, clinical features, and laboratory findings that contribute to this condition.
Methods
A comprehensive literature search was conducted across eight databases from inception to September 1, 2024. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was conducted using univariate and multivariate analyses with Revman 5.3, while heterogeneity was addressed through subgroup and sensitivity analyses. Publication bias was assessed using funnel plots and Egger tests via Stata 15.0.
Results
Seventeen high-quality studies meeting the inclusion criteria were incorporated into this meta-analysis. Independent risk factors for TP in SLE included age (Demographic Features), serositis, splenomegaly, blood system involvement, and renal involvement (Clinical Features), as well as cardiac involvement, anemia, leukocytopenia, low C3/C4, ACA, and CRP (Laboratory Findings). Arthritis and rash were protective factors. Subgroup analysis addressed heterogeneity caused by unit and sample size differences. Sensitivity analysis comparing the consistency between fixed-effects model (FEM) and random-effects model (REM) confirmed the reliability of the findings, and both funnel plots and Egger tests suggested no publication bias.
Conclusion
This meta-analysis identified several potential independent risk factors for TP in SLE. Early screening and timely intervention for patients with these risk factors are essential to reduce the likelihood of TP, prevent severe organ damage, and improve overall prognosis.
{"title":"Risk factors associated with thrombocytopenia in systemic lupus erythematosus: A systematic review and meta-analysis","authors":"Ze Yang , Yanzuo Wu , Shuo Huang , Jie Bao , Li Xu , Yongsheng Fan","doi":"10.1016/j.autrev.2024.103721","DOIUrl":"10.1016/j.autrev.2024.103721","url":null,"abstract":"<div><h3>Background</h3><div>Systemic lupus erythematosus (SLE) frequently manifests with thrombocytopenia (TP), a hematologic complication that heightens the risk of severe outcomes and increases mortality. This meta-analysis aims to evaluate the potential risk factors associated with TP in SLE patients, providing insights into the demographic features, clinical features, and laboratory findings that contribute to this condition.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted across eight databases from inception to September 1, 2024. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was conducted using univariate and multivariate analyses with Revman 5.3, while heterogeneity was addressed through subgroup and sensitivity analyses. Publication bias was assessed using funnel plots and Egger tests via Stata 15.0.</div></div><div><h3>Results</h3><div>Seventeen high-quality studies meeting the inclusion criteria were incorporated into this meta-analysis. Independent risk factors for TP in SLE included age (Demographic Features), serositis, splenomegaly, blood system involvement, and renal involvement (Clinical Features), as well as cardiac involvement, anemia, leukocytopenia, low C3/C4, ACA, and CRP (Laboratory Findings). Arthritis and rash were protective factors. Subgroup analysis addressed heterogeneity caused by unit and sample size differences. Sensitivity analysis comparing the consistency between fixed-effects model (FEM) and random-effects model (REM) confirmed the reliability of the findings, and both funnel plots and Egger tests suggested no publication bias.</div></div><div><h3>Conclusion</h3><div>This meta-analysis identified several potential independent risk factors for TP in SLE. Early screening and timely intervention for patients with these risk factors are essential to reduce the likelihood of TP, prevent severe organ damage, and improve overall prognosis.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 2","pages":"Article 103721"},"PeriodicalIF":9.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.autrev.2024.103717
Yaru Qiao , Changer He , Yuxuan Xia , Dickson Kofi Wiredu Ocansey , Fei Mao
Intestinal mucus, a viscoelastic medium with mucin2 (MUC2) as its main component, covers the surface of intestinal epithelial cells and protects the intestine from invasion, forming the first barrier of the intestinal tract. Unlike the small intestine, where the mucus layer is a single layer, the colonic mucus layer can be divided into a sterile inner layer and an outer layer with bacterial colonization. Many of the substances in the mucus layer have beneficial effects on the intestinal epithelium, but the mucus layer is often affected by a variety of factors, mainly microbiological, dietary, and immunological. Inflammatory bowel disease (IBD) is a disease of increasing morbidity worldwide, with a complex etiology and a high relapse rate. In recent years, the mucus barrier in IBD has received increasing attention and is considered a key factor in the pathogenesis of IBD. Loss of goblet cells (GCs) and changes in the composition and properties of the mucus layer material are commonly found in the colon of IBD patients. Damage to the mucus layer may make it easier for microorganisms to access the intestinal epithelium and cause inflammation. There are currently a number of herbs and other therapies that can be used to treat IBD and repair the damaged mucus barrier. This review highlights the important role of the mucus layer in IBD and the therapies that target the mucus layer in IBD.
{"title":"Intestinal mucus barrier: A potential therapeutic target for IBD","authors":"Yaru Qiao , Changer He , Yuxuan Xia , Dickson Kofi Wiredu Ocansey , Fei Mao","doi":"10.1016/j.autrev.2024.103717","DOIUrl":"10.1016/j.autrev.2024.103717","url":null,"abstract":"<div><div>Intestinal mucus, a viscoelastic medium with mucin2 (MUC2) as its main component, covers the surface of intestinal epithelial cells and protects the intestine from invasion, forming the first barrier of the intestinal tract. Unlike the small intestine, where the mucus layer is a single layer, the colonic mucus layer can be divided into a sterile inner layer and an outer layer with bacterial colonization. Many of the substances in the mucus layer have beneficial effects on the intestinal epithelium, but the mucus layer is often affected by a variety of factors, mainly microbiological, dietary, and immunological. Inflammatory bowel disease (IBD) is a disease of increasing morbidity worldwide, with a complex etiology and a high relapse rate. In recent years, the mucus barrier in IBD has received increasing attention and is considered a key factor in the pathogenesis of IBD. Loss of goblet cells (GCs) and changes in the composition and properties of the mucus layer material are commonly found in the colon of IBD patients. Damage to the mucus layer may make it easier for microorganisms to access the intestinal epithelium and cause inflammation. There are currently a number of herbs and other therapies that can be used to treat IBD and repair the damaged mucus barrier. This review highlights the important role of the mucus layer in IBD and the therapies that target the mucus layer in IBD.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 2","pages":"Article 103717"},"PeriodicalIF":9.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the loss of insulin-producing cells in the pancreatic islets. Patients with T1D have autoreactive CD4+ and CD8+ T cells that show specific features, indicating previous exposure to self-antigens. Despite that memory T cells are vital components of the adaptive immune system, providing enduring protection against pathogens; individuals with T1D have a higher proportion of memory T cells compared to healthy individuals with naїve phenotypes. Targeting memory T cells in newly diagnosed T1D patients has shown promising results, providing evidence for the significant role of memory T cells in this disease. There are various types of memory T cells, each with unique characteristics and functions. Recent advancements in understanding the complexity and heterogeneity of T cell subpopulations have shown that T1D cannot be fully understood through simple categorization. This review aims to discuss various types of memory T cells in the immunopathogenesis of T1D, focusing on their phenotypes and frequencies, as well as epigenetic and metabolic alterations. Additionally, it will address novel immunotherapeutic approaches targeting memory T cell subsets in T1D.
{"title":"The role of memory T cells in type 1 diabetes: Phenotypes, mechanisms, and therapeutic implications","authors":"Pooria Fazeli , Shiva Abolhasani , Negin Karamali , Mahsa Hajivalili , Gholamreza Daryabor , Mohammad Panji , Maryam Karimian , Maryam Hosseini","doi":"10.1016/j.autrev.2025.103759","DOIUrl":"10.1016/j.autrev.2025.103759","url":null,"abstract":"<div><div>Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the loss of insulin-producing cells in the pancreatic islets. Patients with T1D have autoreactive CD4<sup>+</sup> and CD8<sup>+</sup> T cells that show specific features, indicating previous exposure to self-antigens. Despite that memory T cells are vital components of the adaptive immune system, providing enduring protection against pathogens; individuals with T1D have a higher proportion of memory T cells compared to healthy individuals with naїve phenotypes. Targeting memory T cells in newly diagnosed T1D patients has shown promising results, providing evidence for the significant role of memory T cells in this disease. There are various types of memory T cells, each with unique characteristics and functions. Recent advancements in understanding the complexity and heterogeneity of T cell subpopulations have shown that T1D cannot be fully understood through simple categorization. This review aims to discuss various types of memory T cells in the immunopathogenesis of T1D, focusing on their phenotypes and frequencies, as well as epigenetic and metabolic alterations. Additionally, it will address novel immunotherapeutic approaches targeting memory T cell subsets in T1D.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 4","pages":"Article 103759"},"PeriodicalIF":9.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-25DOI: 10.1016/j.autrev.2025.103758
Daya Krishna Jha , Rinkalben Kakadiya , Ananya Sharma , Shankar Naidu , Dipankar De , Vishal Sharma
Tuberculosis (TB), caused by Mycobacterium tuberculosis , is the most significant infectious cause of mortality across the globe. While TB disease can prey on immunocompetent individuals, it is more likely to occur in immunocompromised individuals. Immune-mediated inflammatory diseases (IMIDs) are a group of diseases (rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, psoriasis, hidradenitis suppurativa, autoimmune blistering diseases, and others) where there may be a need for systemic immunosuppression to control the disease manifestations, treat symptoms and improve long term outcomes. Immunosuppression may predispose them to active TB either from recent infection or reactivation of Latent TB (LTB). The major determinants of reactivation include the type of therapy (highest risk with TNF inhibitors and JAK inhibitors) and the underlying TB endemicity. The strategy to avoid TB reactivation includes the detection of LTB using tests that detect immunoreactivity to TB antigens (interferon-gamma release assays or tuberculin skin test) and treating LTB before or with initiation of IMID therapies. Available diagnostic tests have deficiencies in diagnostic sensitivity to detect LTB and even worse capability in predicting reactivation of TB. In addition to immunological tests, more stringent testing strategy utilizing one or many LTB equivalents may point towards subclinical TB. LTB equivalents include clinical (past history of TB, recent exposure to TB) and radiological criteria (use of chest roentgenogram, computed tomography, or, sometimes positron emission tomography – computed tomography). The present review summarizes the risk factors for TB reactivation in patients initiated on advanced therapies, geographically appropriate strategies for LTB testing, and treatment of LTB.
{"title":"Assessment and management for latent tuberculosis before advanced therapies for immune-mediated inflammatory diseases: A comprehensive review","authors":"Daya Krishna Jha , Rinkalben Kakadiya , Ananya Sharma , Shankar Naidu , Dipankar De , Vishal Sharma","doi":"10.1016/j.autrev.2025.103758","DOIUrl":"10.1016/j.autrev.2025.103758","url":null,"abstract":"<div><div>Tuberculosis (TB), caused by <em>Mycobacterium tuberculosis ,</em> is the most significant infectious cause of mortality across the globe. While TB disease can prey on immunocompetent individuals, it is more likely to occur in immunocompromised individuals. Immune-mediated inflammatory diseases (IMIDs) are a group of diseases (rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, psoriasis, hidradenitis suppurativa, autoimmune blistering diseases, and others) where there may be a need for systemic immunosuppression to control the disease manifestations, treat symptoms and improve long term outcomes. Immunosuppression may predispose them to active TB either from recent infection or reactivation of Latent TB (LTB). The major determinants of reactivation include the type of therapy (highest risk with TNF inhibitors and JAK inhibitors) and the underlying TB endemicity. The strategy to avoid TB reactivation includes the detection of LTB using tests that detect immunoreactivity to TB antigens (interferon-gamma release assays or tuberculin skin test) and treating LTB before or with initiation of IMID therapies. Available diagnostic tests have deficiencies in diagnostic sensitivity to detect LTB and even worse capability in predicting reactivation of TB. In addition to immunological tests, more stringent testing strategy utilizing one or many LTB equivalents may point towards subclinical TB. LTB equivalents include clinical (past history of TB, recent exposure to TB) and radiological criteria (use of chest roentgenogram, computed tomography, or, sometimes positron emission tomography – computed tomography). The present review summarizes the risk factors for TB reactivation in patients initiated on advanced therapies, geographically appropriate strategies for LTB testing, and treatment of LTB.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 3","pages":"Article 103758"},"PeriodicalIF":9.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-23DOI: 10.1016/j.autrev.2025.103756
Amanda Carolina Miranda Costa, Diego de Paula Ferreira Nunes, Paulo Rogério Júlio, Rodrigo Marchi Silva, Bruna Martins De Aquino, Samuel De Andrade, Danilo Rodrigues Pereira, Tais Nitsch Mazzola, Jean Marcos De Souza, Alberto Rolim Muro Martinez, Marcondes Cavalcante França, Fabiano Reis, Zahi Touma, Timothy B Niewold, Simone Appenzeller
Introduction: Autoimmune diseases often present in a systemic manner, affecting various organs and tissues. Involvement of the central and peripheral nervous system is not uncommon in these conditions and is associated with high morbidity and mortality. Therefore, early recognition of the neuropsychiatric manifestations associated with rheumatologic diseases is essential for the introduction of appropriate therapies with the objective of providing a better quality of life for individuals.
Objective: To provide a literature review of the neuropsychiatric manifestations related to Systemic Lupus Erythematosus (SLE) and primary Sjögren's Disease (pSD), through the description of signs, symptoms, and immunological variables associated with these conditions.
Methods: A literature review was conducted by searching for national and international articles available in the SciELO and PubMed databases related to the description of neurological and psychiatric manifestations in patients with the rheumatologic diseases of interest in this study.
Results: The main NP manifestations presented in SLE and pSD are discussed, focusing on clinical presentation and etiology. Treatment option are, however, mainly based on expert opinion, since a few randomized controlled trials have been done.
Conclusions: There is a high prevalence of neuropsychiatric manifestations associated with SLE and pSD. The variety of physiopathology pathways may explain the variety of symptoms, however pathological findings are rare. Multicenter studies on attribution protocols and treatment are necessary to address the current gaps.
{"title":"Neuropsychiatric manifestations in systemic lupus erythematosus and Sjogren's disease.","authors":"Amanda Carolina Miranda Costa, Diego de Paula Ferreira Nunes, Paulo Rogério Júlio, Rodrigo Marchi Silva, Bruna Martins De Aquino, Samuel De Andrade, Danilo Rodrigues Pereira, Tais Nitsch Mazzola, Jean Marcos De Souza, Alberto Rolim Muro Martinez, Marcondes Cavalcante França, Fabiano Reis, Zahi Touma, Timothy B Niewold, Simone Appenzeller","doi":"10.1016/j.autrev.2025.103756","DOIUrl":"https://doi.org/10.1016/j.autrev.2025.103756","url":null,"abstract":"<p><strong>Introduction: </strong>Autoimmune diseases often present in a systemic manner, affecting various organs and tissues. Involvement of the central and peripheral nervous system is not uncommon in these conditions and is associated with high morbidity and mortality. Therefore, early recognition of the neuropsychiatric manifestations associated with rheumatologic diseases is essential for the introduction of appropriate therapies with the objective of providing a better quality of life for individuals.</p><p><strong>Objective: </strong>To provide a literature review of the neuropsychiatric manifestations related to Systemic Lupus Erythematosus (SLE) and primary Sjögren's Disease (pSD), through the description of signs, symptoms, and immunological variables associated with these conditions.</p><p><strong>Methods: </strong>A literature review was conducted by searching for national and international articles available in the SciELO and PubMed databases related to the description of neurological and psychiatric manifestations in patients with the rheumatologic diseases of interest in this study.</p><p><strong>Results: </strong>The main NP manifestations presented in SLE and pSD are discussed, focusing on clinical presentation and etiology. Treatment option are, however, mainly based on expert opinion, since a few randomized controlled trials have been done.</p><p><strong>Conclusions: </strong>There is a high prevalence of neuropsychiatric manifestations associated with SLE and pSD. The variety of physiopathology pathways may explain the variety of symptoms, however pathological findings are rare. Multicenter studies on attribution protocols and treatment are necessary to address the current gaps.</p>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":" ","pages":"103756"},"PeriodicalIF":9.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><h3>Background</h3><div>Dilated cardiomyopathy (DCM) is a prevalent myocardial disorder characterized by impaired cardiac function affecting either the left ventricle or both ventricles. Accumulating evidence suggests that autoimmunity represents a key mechanism implicated in its pathogenesis, as several abundant autoantibodies have been identified in patients with the condition. However, the prevalence of these antibodies (Abs) in patients with DCM compared to that in both healthy controls (HCs) and those with ischemic cardiomyopathy (ICM), as well as their potential association with DCM, remains unclear. This study aimed to elucidate the prevalence of certain autoantibodies in patients with DCM compared to that in HCs and patients with ICM, as well as to evaluate their correlation with clinical characteristics and outcomes.</div></div><div><h3>Methods</h3><div>A comprehensive literature search of the PubMed, Web of Science, EMBASE, the Cochrane Library, and Scopus was conducted up to March 26, 2024, and any article that fulfilled our inclusion criteria was reviewed. A meta-analysis was then conducted, using both random- and fixed-effects models.</div></div><div><h3>Results</h3><div>A total of 38 studies met the inclusion criteria and were pulled for this analysis. Significantly higher prevalence rates of autoantibodies targeting the anti-β1 adrenergic receptor (β1-AR; odds ratio [OR] = 4.96, <em>p</em> = 0.000), M2 muscarinic receptor (M2-R; OR = 4.07, p = 0.000), adenine nucleotide translocator (ANT; OR = 21.18, <em>p</em> = 0.001) and myosin (OR = 12.26, <em>p</em> = 0.000) were observed in patients with DCM compared to HCs. Moreover, patients with DCM exhibited a significantly higher frequency of positive ANT Abs (OR = 34.52, <em>p</em> = 0.005) compared to those with ICM. Regarding clinical characteristics and outcomes, seropositivity for β1-AR Abs was found to be significantly correlated with New York Heart Association (NYHA) classification (standardized mean difference [SMD] = 0.78, <em>p</em> = 0.006), left ventricular ejection fraction (LVEF) (SMD = −1.38, <em>p</em> = 0.001), and heart rate (HR) (SMD = 1.505, <em>p</em> = 0.022). Seropositivity for anti‑calcium channel Abs was significantly associated with sudden cardiac death (SCD; OR = 3.17, <em>p</em> = 0.000) and all-cause mortality (OR = 2.06, <em>p</em> = 0.008), while anti-troponin I (TnI) Abs were associated with atrial fibrillation (OR = 0.21, <em>p</em> = 0.042). In terms of Ab prevalence rates, significant heterogeneity in the frequency of anti-β1-AR Abs between studies investigating DCM and ICM may be partially explained by the detection methods used and the mean ages of the patients. Meta-regression analysis suggested that the patients' ages may partially explain the observed heterogeneity between studies regarding β1-AR Ab seropositivity and HR. However, the heterogeneity observed in the studies comparing the prevalences of Abs in patients with DCM vs HCs and ICM, as
{"title":"Frequency of autoantibodies and their associated clinical characteristics and outcomes in patients with dilated cardiomyopathy: A systematic review and meta-analysis","authors":"Jingdi Zhang , Honglin Xu, Zhan Li, Futai Feng, Siyu Wang, Yongzhe Li","doi":"10.1016/j.autrev.2025.103755","DOIUrl":"10.1016/j.autrev.2025.103755","url":null,"abstract":"<div><h3>Background</h3><div>Dilated cardiomyopathy (DCM) is a prevalent myocardial disorder characterized by impaired cardiac function affecting either the left ventricle or both ventricles. Accumulating evidence suggests that autoimmunity represents a key mechanism implicated in its pathogenesis, as several abundant autoantibodies have been identified in patients with the condition. However, the prevalence of these antibodies (Abs) in patients with DCM compared to that in both healthy controls (HCs) and those with ischemic cardiomyopathy (ICM), as well as their potential association with DCM, remains unclear. This study aimed to elucidate the prevalence of certain autoantibodies in patients with DCM compared to that in HCs and patients with ICM, as well as to evaluate their correlation with clinical characteristics and outcomes.</div></div><div><h3>Methods</h3><div>A comprehensive literature search of the PubMed, Web of Science, EMBASE, the Cochrane Library, and Scopus was conducted up to March 26, 2024, and any article that fulfilled our inclusion criteria was reviewed. A meta-analysis was then conducted, using both random- and fixed-effects models.</div></div><div><h3>Results</h3><div>A total of 38 studies met the inclusion criteria and were pulled for this analysis. Significantly higher prevalence rates of autoantibodies targeting the anti-β1 adrenergic receptor (β1-AR; odds ratio [OR] = 4.96, <em>p</em> = 0.000), M2 muscarinic receptor (M2-R; OR = 4.07, p = 0.000), adenine nucleotide translocator (ANT; OR = 21.18, <em>p</em> = 0.001) and myosin (OR = 12.26, <em>p</em> = 0.000) were observed in patients with DCM compared to HCs. Moreover, patients with DCM exhibited a significantly higher frequency of positive ANT Abs (OR = 34.52, <em>p</em> = 0.005) compared to those with ICM. Regarding clinical characteristics and outcomes, seropositivity for β1-AR Abs was found to be significantly correlated with New York Heart Association (NYHA) classification (standardized mean difference [SMD] = 0.78, <em>p</em> = 0.006), left ventricular ejection fraction (LVEF) (SMD = −1.38, <em>p</em> = 0.001), and heart rate (HR) (SMD = 1.505, <em>p</em> = 0.022). Seropositivity for anti‑calcium channel Abs was significantly associated with sudden cardiac death (SCD; OR = 3.17, <em>p</em> = 0.000) and all-cause mortality (OR = 2.06, <em>p</em> = 0.008), while anti-troponin I (TnI) Abs were associated with atrial fibrillation (OR = 0.21, <em>p</em> = 0.042). In terms of Ab prevalence rates, significant heterogeneity in the frequency of anti-β1-AR Abs between studies investigating DCM and ICM may be partially explained by the detection methods used and the mean ages of the patients. Meta-regression analysis suggested that the patients' ages may partially explain the observed heterogeneity between studies regarding β1-AR Ab seropositivity and HR. However, the heterogeneity observed in the studies comparing the prevalences of Abs in patients with DCM vs HCs and ICM, as","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 4","pages":"Article 103755"},"PeriodicalIF":9.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1016/j.autrev.2025.103757
Md Rakibul Alam , Amos Olalekan Akinyemi , Jianlin Wang , Mithu Howlader , Mohammad Esfini Farahani , Maria Nur , Min Zhang , Lixiang Gu , Zhiguo Li
CD4+ and CD8+ T cells play critical roles in both innate and adaptive immune responses, managing and modulating cellular immunity during immune diseases and cancer. Their well-established functions have led to significant clinical benefits. CD4+CD8+ double-positive (DP) T cells, a subset of the T cell population, have been identified in the blood and peripheral lymphoid tissues across various species. They have gained interest due to their involvement in immune disorders, inflammation, and cancer. Although mature DP T cells are present in healthy individuals and contribute to disease contexts, their molecular characteristics and pathophysiological roles remain debated. Notably, the number of DP T cells in the blood is higher in older adults compared to younger individuals, and these cells can stimulate inflammation and viral infections through increased secretion of interleukin (IL)-10, interferon gamma (IFN-γ), and transforming growth factor beta (TGF-β). In cancer, DP T cells have been observed to infiltrate cutaneous T cell lymphomas and are found in greater numbers in nodular lymphocyte predominant Hodgkin lymphoma, melanoma, hepatocellular carcinoma, and breast cancer. The higher prevalence of DP T cells in advanced cancers, coupled with their strong lytic activity and distinct cytokine profile, suggests that these cells may play a crucial role in modulating immune responses to cancer. This insight offers a potential new approach for enhancing the identification and selection of antigen-reactive T cells in immune-based treatments. This review provides a comprehensive overview of the origin, distribution, transcriptional regulation during developmental stages, and functions of DP T cells. A deeper understanding of the diversity and roles of DP T cells may pave the way for their development as a promising tool for immunotherapy in the management of immune disorders and metastatic cancers.
CD4+ 和 CD8+ T 细胞在先天性免疫反应和适应性免疫反应中发挥关键作用，在免疫疾病和癌症期间管理和调节细胞免疫。CD4+和CD8+双阳性（CD4+CD8+ double-positive，CD4+CD8+双阳性）T细胞的功能已得到公认，并为临床带来了显著的益处。CD4+CD8+ 双阳性（DP）T 细胞是 T 细胞群的一个亚群，已在不同物种的血液和外周淋巴组织中发现。由于它们参与免疫失调、炎症和癌症，因此备受关注。虽然成熟的 DP T 细胞存在于健康人体内，并对疾病有一定的影响，但它们的分子特征和病理生理作用仍存在争议。值得注意的是，与年轻人相比，老年人血液中的 DP T 细胞数量更高，这些细胞可通过增加分泌白细胞介素（IL）-10、γ 干扰素（IFN-γ）和转化生长因子 beta（TGF-β）来刺激炎症和病毒感染。在癌症中，已观察到 DP T 细胞浸润皮肤 T 细胞淋巴瘤，并在结节性淋巴细胞占优势的霍奇金淋巴瘤、黑色素瘤、肝细胞癌和乳腺癌中发现较多 DP T 细胞。DP T 细胞在晚期癌症中发病率较高，加上它们具有很强的溶解活性和独特的细胞因子特征，表明这些细胞可能在调节癌症免疫反应方面发挥着至关重要的作用。这一观点为在基于免疫的治疗中加强识别和选择抗原反应性 T 细胞提供了一种潜在的新方法。本综述全面概述了 DP T 细胞的起源、分布、发育阶段的转录调控和功能。对 DP T 细胞的多样性和作用的深入了解可能会为它们发展成为治疗免疫紊乱和转移性癌症的一种有前途的免疫疗法工具铺平道路。
{"title":"CD4+CD8+ double-positive T cells in immune disorders and cancer: Prospects and hurdles in immunotherapy","authors":"Md Rakibul Alam , Amos Olalekan Akinyemi , Jianlin Wang , Mithu Howlader , Mohammad Esfini Farahani , Maria Nur , Min Zhang , Lixiang Gu , Zhiguo Li","doi":"10.1016/j.autrev.2025.103757","DOIUrl":"10.1016/j.autrev.2025.103757","url":null,"abstract":"<div><div>CD4<sup>+</sup> and CD8<sup>+</sup> T cells play critical roles in both innate and adaptive immune responses, managing and modulating cellular immunity during immune diseases and cancer. Their well-established functions have led to significant clinical benefits. CD4<sup>+</sup>CD8<sup>+</sup> double-positive (DP) T cells, a subset of the T cell population, have been identified in the blood and peripheral lymphoid tissues across various species. They have gained interest due to their involvement in immune disorders, inflammation, and cancer. Although mature DP T cells are present in healthy individuals and contribute to disease contexts, their molecular characteristics and pathophysiological roles remain debated. Notably, the number of DP T cells in the blood is higher in older adults compared to younger individuals, and these cells can stimulate inflammation and viral infections through increased secretion of interleukin (IL)-10, interferon gamma (IFN-γ), and transforming growth factor beta (TGF-β). In cancer, DP T cells have been observed to infiltrate cutaneous T cell lymphomas and are found in greater numbers in nodular lymphocyte predominant Hodgkin lymphoma, melanoma, hepatocellular carcinoma, and breast cancer. The higher prevalence of DP T cells in advanced cancers, coupled with their strong lytic activity and distinct cytokine profile, suggests that these cells may play a crucial role in modulating immune responses to cancer. This insight offers a potential new approach for enhancing the identification and selection of antigen-reactive T cells in immune-based treatments. This review provides a comprehensive overview of the origin, distribution, transcriptional regulation during developmental stages, and functions of DP T cells. A deeper understanding of the diversity and roles of DP T cells may pave the way for their development as a promising tool for immunotherapy in the management of immune disorders and metastatic cancers.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 3","pages":"Article 103757"},"PeriodicalIF":9.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20DOI: 10.1016/j.autrev.2025.103754
Franz Felix Konen , Nora Möhn , Torsten Witte , Matthias Schefzyk , Miriam Wiestler , Svjetlana Lovric , Karsten Hufendiek , Konstantin Fritz Jendretzky , Stefan Gingele , Philipp Schwenkenbecher , Kurt-Wolfram Sühs , Manuel A. Friese , Luisa Klotz , Refik Pul , Marc Pawlitzki , David Hagin , Christoph Kleinschnitz , Sven G. Meuth , Thomas Skripuletz
A wide variety of immunomodulatory therapies are already available for the treatment of multiple sclerosis (MS). Through fundamental insights from basic research with a gain of knowledge in the pathological processes underlying MS, the exploration of additional medical compounds within clinical trials has been ignited. Emerging novel medications with innovative mechanisms of action are being introduced. Those mechanisms of action include a broad therapeutic spectrum of substances targeting various protein kinases, some of which could also be used for the treatment of other autoimmune-mediated diseases. The advancement of new compounds could therefore enable a more personalized approach in treating MS, taking into consideration patients' co-existing autoimmune-mediated diseases. In this review, we discuss potential compounds targeting protein kinases, currently under investigation in clinical trials for various autoimmune diseases that could become viable treatment options for MS and comorbid autoimmune conditions in the future.
{"title":"Disease-modifying strategies: Targeting protein kinases in multiple sclerosis and other autoimmune disorders","authors":"Franz Felix Konen , Nora Möhn , Torsten Witte , Matthias Schefzyk , Miriam Wiestler , Svjetlana Lovric , Karsten Hufendiek , Konstantin Fritz Jendretzky , Stefan Gingele , Philipp Schwenkenbecher , Kurt-Wolfram Sühs , Manuel A. Friese , Luisa Klotz , Refik Pul , Marc Pawlitzki , David Hagin , Christoph Kleinschnitz , Sven G. Meuth , Thomas Skripuletz","doi":"10.1016/j.autrev.2025.103754","DOIUrl":"10.1016/j.autrev.2025.103754","url":null,"abstract":"<div><div>A wide variety of immunomodulatory therapies are already available for the treatment of multiple sclerosis (MS). Through fundamental insights from basic research with a gain of knowledge in the pathological processes underlying MS, the exploration of additional medical compounds within clinical trials has been ignited. Emerging novel medications with innovative mechanisms of action are being introduced. Those mechanisms of action include a broad therapeutic spectrum of substances targeting various protein kinases, some of which could also be used for the treatment of other autoimmune-mediated diseases. The advancement of new compounds could therefore enable a more personalized approach in treating MS, taking into consideration patients' co-existing autoimmune-mediated diseases. In this review, we discuss potential compounds targeting protein kinases, currently under investigation in clinical trials for various autoimmune diseases that could become viable treatment options for MS and comorbid autoimmune conditions in the future.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 4","pages":"Article 103754"},"PeriodicalIF":9.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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