{"title":"Exploring the role of gut microbiome in autoimmune diseases: A comprehensive review","authors":"","doi":"10.1016/j.autrev.2024.103654","DOIUrl":"10.1016/j.autrev.2024.103654","url":null,"abstract":"<div><div>As the industrialized society advances, there has been a gradual increase in the prevalence of autoimmune disorders. A probe into the fundamental causes has disclosed several factors in modern society that have an influence on the gut microbiome. These dramatic shifts in the gut microbiome are likely to be one of the reasons for the disarray in the immune system, and the relationship between the immune system and the gut microbiome emerging as a perennial hot topic of research. This review enumerates the findings from sequencing studies of gut microbiota on seven autoimmune diseases (ADs): Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Ankylosing Spondylitis (AS), Systemic Sclerosis (SSc), Sjögren's Syndrome (SjS), Juvenile Idiopathic Arthritis (JIA), and Behçet's Disease (BD). It aims to identify commonalities in changes in the gut microbiome within the autoimmune disease cohort and characteristics specific to each disease. The dysregulation of the gut microbiome involves a disruption of the internal balance and the balance between the external environment and the host. This dysregulation impacts the host's immune system, potentially playing a role in the development of ADs. Damage to the gut epithelial barrier allows potential pathogens to translocate to the mucosal layer, contacting epithelial cells, disrupting tight junctions, and being recognized by antigen-presenting cells, which triggers an immune response. Primed T-cells assist B-cells in producing antibodies against pathogens; if antigen mimicry occurs, an immune response is generated in extraintestinal organs during immune cell circulation, clinically manifesting as ADs. However, current research is limited; advancements in sequencing technology, large-scale cohort studies, and fecal microbiota transplantation (FMT) research are expected to propel this field to new peaks.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387552","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}
{"title":"Prevention of rheumatoid arthritis using a familial predictive medicine approach","authors":"","doi":"10.1016/j.autrev.2024.103653","DOIUrl":"10.1016/j.autrev.2024.103653","url":null,"abstract":"<div><div>Most of the chronic-degenerative diseases deserve a very early recognition of symptoms and signs for the earliest secondary prevention, which could be also very useful in many cases for the most precocious clinical approach. The periodic monitoring of a subject at risk of a specific disease, because of genomic predisposition by predictive medicine approach, may help to earlier detection of onset and/or the progression of the pathology itself, through intra-individual monitoring. This is particularly the case of rheumatoid arthritis (RA) for which an early diagnosis is undoubtedly the first step to ensure the most proper therapy for the patient. Thus, the earlier identification of individuals at high risk of RA could lead to ultra-preventive strategies to start for the best lifestyle performances and/or for any other effective therapeutic interventions to contrast the onset, and/or the evolution of the putative RA. This will also optimize both costs and medical resources, according to the health care policies of many countries.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380000","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}
{"title":"Impact of non-immunosuppressive medical therapy on disease progression and complications of Takayasu arteritis: A narrative review","authors":"","doi":"10.1016/j.autrev.2024.103656","DOIUrl":"10.1016/j.autrev.2024.103656","url":null,"abstract":"<div><div>Takayasu's arteritis is a rare large vessel vasculitis typically affecting young Asian women. It causes inflammation of the aorta and its major branches, leading to stenosis and aneurysmal dilations, and increasing cardiovascular morbidity due to accelerated atherosclerosis. Although glucocorticoids are effective for acute disease control and preliminary data on immunosuppressive drugs are promising, standardized treatment protocols are lacking. The use of prophylactic treatments with antihypertensives, antiplatelets, anticoagulants, and lipid-lowering drugs to prevent thrombotic and ischemic complications remains debated. This study reviews the evidence on the effectiveness of non-immunosuppressive medical therapy in Takayasu's arteritis. A search of the PubMed database identified eleven studies involving 204 patients. Antiplatelets: data on 68 patients were mixed, in fact low-dose aspirin did not prevent major cardiovascular events in 36 patients, but higher doses reduced ischemic complications in 24 patients. Anticoagulants: no data on new oral anticoagulants were available, and vitamin K antagonists in 9 patients did not alter cardiovascular complications. Antihypertensives: ACE-inhibitors controlled blood pressure in patients with renovascular hypertension but increased the risk of acute renal function decline, while β-blockers reduced the symptoms and the progression of myocardial hypertrophy in patients with heart failure and aortic regurgitation. Statins: data from two cohorts showed that while statins reduced the recurrence rate of arteritis in 30 patients, they did not affect recurrence rates or cardiovascular complications in 13 patients. Overall, current evidence, although not definitive, supports the use of non-immunosuppressive medical treatments to prevent long-term complications and damage in Takayasu's arteritis, considering the disease's pathophysiological mechanisms and increased cardiovascular risk. Further research is strongly encouraged.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387553","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}
{"title":"Analysis of global prevalence, DALY and trends of inflammatory bowel disease and their correlations with sociodemographic index: Data from 1990 to 2019","authors":"","doi":"10.1016/j.autrev.2024.103655","DOIUrl":"10.1016/j.autrev.2024.103655","url":null,"abstract":"<div><h3>Background</h3><div>Inflammatory bowel disease (IBD) is a kind of chronic inflammatory disorders of the gastrointestinal tract with diverse prevalence rates and patterns globally. Accurate comprehension of the disease's epidemiological characteristics is imperative for disease control and prevention all over the world.</div></div><div><h3>Objective</h3><div>To provide the most updated estimates on the global burden of IBD using the 2019 Global Burden of Disease (GBD) study data, to systematically analyze the IBD epidemiological characteristics at the global, regional, and national levels including the prevalence, incidence, and disability-adjusted life years (DALY) rates, and to analyze the correlations of the socioeconomic development level with IBD epidemiological characteristics.</div></div><div><h3>Methods</h3><div>We conducted an overall analysis of the global, regional, and national burden of IBD from 1990 to 2019, data from the 2019 GBD study. The GBD's classification of the world into 21 regions and 204 countries and territories facilitated a thorough examination. Age-standardized estimated annual percentage changes (EAPCs) were computed to assess the temporal trends in IBD age-standardized rates (ASRs), with age standardization employed to mitigate potential confounding effects from age structure. The sociodemographic Index (SDI) was used to correlate the socioeconomic development level with the epidemiological characteristics of IBD.</div></div><div><h3>Results</h3><div>From 1990 to 2019, the global age-standardized prevalence, incidence, and DALY rates of IBD remained high. There was a slight downward trend in the global age-standardized incidence and DALY rates of IBD and men exhibited higher DALY rates than women. In 2019, high-income North America recorded the highest age-standardized prevalence, incidence, and DALY rates, while Oceania had the lowest age-standardized prevalence and incidence rates. South Asia had the lowest age-standardized DALY rates. The age-standardized mortality and DALY rates decreased as SDI values increased and remained higher than the expected levels over the past three decades. A negative correlation was observed between age-standardized DALY rates and SDI at the national level.</div></div><div><h3>Conclusions</h3><div>This analysis of the GBD 2019 database demonstrates that the overall global burden of IBD is still high. Meanwhile, an increasing disease burden is observed in the middle and low SDI locations.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375003","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}
{"title":"Intima media thickness of the carotid artery in primary antiphospholipid syndrome: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.autrev.2024.103657","DOIUrl":"10.1016/j.autrev.2024.103657","url":null,"abstract":"<div><h3>Background</h3><div>Primary antiphospholipid syndrome (PAPS) has been associated with an increase in clinical events associated with atherosclerotic vascular disease. Intima media thickness (IMT) of carotid arteries is a surrogate marker of atherosclerotic vascular disease.</div></div><div><h3>Objectives</h3><div>To conduct a systematic review and meta-analysis of studies evaluating IMT and their clinical correlates in PAPS.</div></div><div><h3>Methods</h3><div>Systematic search of EMBASE and PubMed databases from January 2000 to December 2023; we employed random effect meta-analyses for continuous outcomes and Peto's odds ratio for rare events.</div></div><div><h3>Results</h3><div>The meta-analysis included 21 studies (20 case control and 1 cohort) showing that PAPS patients (<em>n</em> = 1103) had thicker IM than controls (<em>n</em> = 832) (<em>p</em> < 0.0001) with wide heterogeneity (<em>I</em><sup><em>2</em></sup> = 86.9 %); PAPS patients (<em>n</em> = 782) also had a greater pooled prevalence of carotid plaques than controls (<em>n</em> = 537) (13.1 % vs 2.97 %, <em>p</em> < 0.0001). A sensitivity analysis by meta-regression indicated that mean age, gender, disease duration, lipid profile, blood pressures, smoking and statin use all explained the heterogeneity variance; a sensitivity analysis by subgroups confirmed smoking status and statin use as explanatory variables with the addition of ethnicity.</div></div><div><h3>Conclusion</h3><div>Atherosclerosis of the carotid artery represents a clinical feature of PAPS in relation to the traditional risk factors and to statin use. Minimising the atherogenic risk with statins could reduce the late arterial atherothrombotic risks of PAPS.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375004","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}
{"title":"Ear abnormalities in chronic fatigue syndrome (CFS), fibromyalgia (FM), Coronavirus-19 infectious disease (COVID) and long-COVID syndrome (PCS), sick-building syndrome (SBS), post-orthostatic tachycardia syndrome (PoTS), and autoimmune/inflammatory syndrome induced by adjuvants (ASIA): A systematic review","authors":"","doi":"10.1016/j.autrev.2024.103606","DOIUrl":"10.1016/j.autrev.2024.103606","url":null,"abstract":"<div><div>Chronic fatigue syndrome (CFS), fibromyalgia (FM), silicone breast implants (SBI), Coronavirus-19 infectious disease (COVID), COVID-19 vaccination (post-COVIDvac-syndrome), Long-COVID syndrome (PCS), sick-building syndrome (SBS), post-orthostatic tachycardia syndrome (PoTS), and autoimmune/ inflammatory syndrome induced by adjuvants (ASIA) are a cluster of poorly understood medical conditions that have in common a group of ill-defined symptoms and dysautonomic features. Most of the clinical findings of this group of diseases are unspecific, such as fatigue, diffuse pain, cognitive impairment, paresthesia, tachycardia, anxiety, and depression. Hearing disturbances and vertigo have also been described in this context, the underlying pathophysiologic process for these conditions might rely on autonomic autoimmune dysbalance.</div><div>The authors procced a literature review regarding to hearing and labyrinthic disturbances in CSF, FM, SBI, COVID, post-COVIDvac-syndrome, PCS, SBS, POTS, and ASIA. The PRISMA guidelines were followed, and the literature reviewed encompassed papers from January 1990 to January 2024.</div><div>After the initial evaluation of the articles found in the search through Pubmed, Scielo and Embase, a total of 172 articles were read and included in this review.</div><div>The prevalence of hearing loss, dizziness, vertigo and tinnitus was described and correlated with the diseases investigated in this study. There are great variability in the frequencies of symptoms found, but cochlear complaints are the most frequent in most studies. Vestibular symptoms are less reported.</div><div>The main pathophysiological mechanisms are discussed. Direct effects of the virus in the inner ear or nervous pathways, impaired vascular perfusion, cross-reaction or autoimmune immunoreactivity, oxidative stress, DNA methylation, epigenetic modifications and gene activation were implicated in the generation of the investigated symptoms.</div><div>In clinical practice, all patients with these autoimmune conditions who have any audiological complaint an ENT consultation followed by an audiometry are needed.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103881","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}
{"title":"The effects of lifestyle interventions on disease activity and quality of life in patients with systemic lupus erythematosus: A systematic review","authors":"","doi":"10.1016/j.autrev.2024.103609","DOIUrl":"10.1016/j.autrev.2024.103609","url":null,"abstract":"<div><h3>Introduction</h3><div>Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting multiple organs, characterized by flares and remission. Treatment aims to reduce flare severity and prevent long-term damage, but remission is often elusive, and patients may still experience flares and a reduced quality of life (QoL). This had led to a growing interest in non-pharmacological therapies to improve patient wellbeing.</div></div><div><h3>Objective</h3><div>We aimed to assess and summarize the efficacy of lifestyle interventions in SLE patients on disease activity and QoL.</div></div><div><h3>Methods</h3><div>A systematic search on lifestyle interventions, SLE, disease activity, and QoL was conducted in PubMed/Medline, Embase and <span><span>Clinicaltrials.gov</span><svg><path></path></svg></span> in August 2024. Included studies were randomized controlled trials on lifestyle interventions in adult SLE patients. Each trial was appraised using Scottish Intercollegiate Guidelines Network (SIGN) criteria, with participant numbers, study duration, intervention type and outcome measures detailed in separate tables.</div></div><div><h3>Results</h3><div>A total of 3564 articles were screened, resulting in the inclusion of 25 randomized controlled trials with 1521 patients. Study quality varied from high (11 studies) to low (6 studies) with considerable intervention heterogeneity. The interventions fell into five categories: physical activity, psychotherapy, lifestyle coaching, supplements and dietary interventions. Physical activity (2 studies, 116 patients), psychotherapy (5 studies, 507 patients) and coaching (1 study with 30 patients) had no significant effect on disease activity, while fish oil supplementation showed a slight benefit in two studies with a total of 102 patients. Quality of life generally improved with physical activity (4 studies with in total 253 patients) and psychotherapy (9 studies with in total 623 patients), with significant mental health benefits, but coaching (3 studies with in total 186 patients) showed no effect.</div></div><div><h3>Conclusion</h3><div>Various lifestyle interventions influence quality of life in SLE patients. Consistent with recent guidelines, both exercise and psychotherapy may positively impact the health-related quality of life in these patients. However, some studies were biased due to self-reported outcomes and the Hawthorne effect, where participants' behavior changed from receiving extra attention. Further research with larger patient cohorts is necessary to reduce the influence of heterogeneity across different studies and to better understand the potential of these promising therapies.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103893","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}
{"title":"Cardiovascular disease in connective tissue disease-associated interstitial lung disease: A systematic review and meta-analysis of observational studies","authors":"","doi":"10.1016/j.autrev.2024.103614","DOIUrl":"10.1016/j.autrev.2024.103614","url":null,"abstract":"<div><h3>Objectives</h3><div>We performed a systematic review and meta-analysis to assess whether patients with connective tissue disease (CTD)-associated interstitial lung diseases (ILD) have an increased prevalence of cardiovascular (CV) disease and to validate associated risk factors.</div></div><div><h3>Methods</h3><div>The PRISMA guidelines and PICO model were followed. We searched PubMed, Embase, Cochrane Library databases, Scopus, and Directory of Open Access Journals from inception to April 2024.</div></div><div><h3>Results</h3><div>Thirteen studies comprising of 12,520 patients were included. Patients with CTD-ILD had a significantly increased risk of CV disease than patients with CTD (relative risk [RR] = 1.65, 95 % confidence interval [CI]: 1.41, 1.93), which are related to the proportion of men (<em>P</em> = 0.001) and the proportion of smokers (<em>P</em> = 0.045). Subgroup analysis found that patients with CTD-ILD had a higher risk of heart failure (RR = 2.84, 95 % CI: 1.50, 5.39), arrhythmia (RR = 1.55, 95 % CI: 1.22, 1.97) than patients with CTD. Another subgroup analysis showed that RA-ILD and SSc-ILD were associated with an increased risk of CV disease, but not IIM-ILD and MCTD-ILD (RA-ILD: RR = 2.19, 95 % CI: 1.27, 3.80; SSc-ILD: RR = 1.53, 95 % CI: 1.29, 1.82). Besides, patients with CTD-ILD had a higher prevalence of pulmonary arterial hypertension (RR = 2.48, 95 % CI: 1.69, 3.63) than patients with CTD.</div></div><div><h3>Conclusions</h3><div>Patients with CTD-ILD had a 1.65 times increased risk of CV than patients with CTD-non-ILD, with increased prevalence of heart failure and arrhythmia. The risk of CV disease in SSc-ILD and RA-ILD is increased and we should pay more attention to male smokers. In addition, compared with CTD patients, CTD-ILD patients had a higher risk of pulmonary arterial hypertension.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118890","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}
{"title":"Helminth derivative tuftsin-phopshorylcholine to treat autoimmunity","authors":"","doi":"10.1016/j.autrev.2024.103601","DOIUrl":"10.1016/j.autrev.2024.103601","url":null,"abstract":"<div><div>Autoimmune diseases (AIDs) affect 5 to 10% of the population. There are more than ∼100 different autoimmune diseases. The AIDs are one of the top 10 causes of death in women under 65; 2nd highest cause of chronic illness; top cause of morbidity in women in the US. The NIH estimates annual direct healthcare costs for autoimmune diseases about $100 billion, in comparison, with cancers investment of $57 billion, heart and stroke cost of $200 billion.</div><div>The current treatments for autoimmune diseases encompasses: steroids, chemotherapy, immunosuppressants, biological drugs, disease specific drugs (like acethylcholine-estherase for myasthenia gravis). The treatments for autooimmune diseases supress the patient immune network, which leads the patients to be more susceptible to infections. Hence, there is a need to develop immunomodulatory small molecules with minimal side effects to treat autoimmune diseases.</div><div>The helminths developed secreting compounds which modulate the human defense pathways in order to develop tolerance and survive in the host environment.</div><div>We have imitated the immunomodulatory activity of the helminth by using a derivative of the helminth secretory molecule.</div><div>A bi-functional small molecule –tuftsin (T)-phosphorylcholine (PC), coined as TPC, was constructed. This chimeric molecule showed its immunomodulatory activity in 4 murine models of autoimmune diseases, attenuating the clinical score and the inflammatory response by immunomodutating the host immune system. <em>Ex-vivo</em> in human peripheral blood mononuclear cells (PBMCs) and biopsies originated from arteries of patients with giant cell arteritis. This paper decipher the mode of action of TPC immunomodulatory activity. Our data propose the potential for this small molecule to be a novel therapy for patients with autoimmune diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003502","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}
{"title":"Immunopathogenesis of systemic lupus erythematosus: An update","authors":"","doi":"10.1016/j.autrev.2024.103648","DOIUrl":"10.1016/j.autrev.2024.103648","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by dysregulated immune responses leading to widespread inflammation and damage in various organs. Environmental factors such as infections, hormonal influences and exposure to ultraviolet light can trigger the disease in genetically predisposed individuals. Genome-wide association studies have identified over 100 susceptibility loci linked to immune regulation, interferon (IFN) signaling and antigen presentation in SLE. In addition, rare cases of monogenic lupus have been instrumental in understanding critical underlying disease mechanisms. Several immunological abnormalities contribute to the loss of self-tolerance and the perpetuation of autoimmune responses in SLE. In particular, defective clearance of apoptotic cells due to defective phagocytosis and complement activation leads to accumulation of self-antigens. Dysregulated innate immune responses activate the adaptive immune system, amplifying the inflammatory response with an important role for type I IFNs. Abnormalities in B cell development and activation lead to the production of autoreactive antibodies, forming immune complexes that cause tissue damage. Similarly, disturbances in T-cell compartments, altered regulatory T-cell functions and altered cytokine production, particularly IFN-α, contribute to tissue damage. Understanding of the immunopathogenesis of SLE is evolving rapidly, with ongoing research identifying new molecular pathways and potential therapeutic targets. Future classifications of SLE are likely to be based on underlying biological pathways rather than clinical and serological signs alone. This review aims to provide a detailed update on the most recent findings regarding the immunopathogenesis of SLE, focusing on the variability of biological pathways and the implications for future therapeutic strategies, in particular chimeric antigen receptor T (CAR T) cells.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340217","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}