Journal of autoimmunity最新文献

{"title":"Pulmonary sarcoidosis: A comprehensive review: Past to present","authors":"John A. Belperio , Michael C. Fishbein , Fereidoun Abtin , Jessica Channick , Shailesh A. Balasubramanian , Joseph P. Lynch III","doi":"10.1016/j.jaut.2023.103107","DOIUrl":"10.1016/j.jaut.2023.103107","url":null,"abstract":"<div><div>Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph nodes. Worldwide it is estimated to affect 2–160/100,000 people and has a mortality rate over 5 years of approximately 7%. For sarcoidosis patients, the cause of death is due to sarcoid in 60% of the cases, of which up to 80% are from advanced cardiopulmonary failure (pulmonary hypertension and respiratory microbial infections) in all races except in Japan were greater than 70% of the sarcoidosis deaths are due to cardiac sarcoidosis.</div><div>Scadding stages for pulmonary sarcoidosis associates with clinical outcomes. Stages I and II have radiographic remission in approximately 30%–80% of cases. Stage III only has a 10%–40% chance of resolution, while stage IV has no change of resolution. Up to 40% of pulmonary sarcoidosis patients progress to stage IV disease with lung parenchyma fibroplasia, bronchiectasis with hilar retraction and fibrocystic disease. These patients are at highest risk for the development of precapillary pulmonary hypertension, which may occur in up to 70% of these patients. Sarcoid patients with pre-capillary pulmonary hypertension can respond to targeted pulmonary arterial hypertension medications. Stage IV fibrocytic sarcoidosis with significant pulmonary physiologic impairment, >20% fibrosis on HRCT or pre-capillary pulmonary hypertension have the highest risk of mortality, which can be >40% at 5-years.</div><div>First line treatment for patients who are symptomatic (cough and dyspnea) with parenchymal infiltrates and abnormal pulmonary function testing (PFT) is oral glucocorticoids, such as prednisone with a typical starting dose of 20–40 mg daily for 2 weeks to 2 months. Prednisone can be tapered over 6–18 months if symptoms, spirometry, PFTs, and radiographs improve. Prolonged prednisone may be required to stabilize disease. Patients requiring prolonged prednisone ≥10 mg/day or those with adverse effects due to glucocorticoids may be prescribed second and third line treatements. Second and third line treatments include immunosuppressive agents (e.g., methotrexate and azathioprine) and anti-tumor necrosis factor (TNF) medication; respectively. Effective treatments for advanced fibrocystic pulmonary disease are being explored. Despite different treatments, relapse rates range from 13% to 75% depending on the stage of sarcoid, number of organs involved, socioeconomic status, and geography.</div></div><div><h3>Conclusion</h3><div>The mortality rate for sarcoidosis over a 5 year follow up is approximately 7%. Unfortunately, 10%–40% of patients with sarcoidosis develop progressive pulmonary disease, and >60% of deaths resulting from sarcoidosis are due to advance cardiopulmonary disease. Oral glucocorticoids are the first line treatment, while methotrexate and azathioprine are considered second and anti-TNF agents are third line treatments","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103107"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677873","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":"Quality of life in sarcoidosis","authors":"Catharina C. Moor ,&nbsp;Ogugua Ndili Obi ,&nbsp;Vivienne Kahlmann ,&nbsp;Katharina Buschulte ,&nbsp;Marlies S. Wijsenbeek","doi":"10.1016/j.jaut.2023.103123","DOIUrl":"10.1016/j.jaut.2023.103123","url":null,"abstract":"<div><div>Having sarcoidosis often has a major impact on quality of life of patients and their families. Improving quality of life is prioritized as most important treatment aim by many patients with sarcoidosis, but current evidence and treatment options are limited. In this narrative review, we describe the impact of sarcoidosis on various aspects of daily life, evaluate determinants of health-related quality of life (HRQoL), and provide an overview of the different patient-reported outcome measures to assess HRQoL in sarcoidosis. Moreover, we review the current evidence for pharmacological and non-pharmacological interventions to improve quality of life for people with sarcoidosis.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103123"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182636","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":"Kidney manifestations of sarcoidosis","authors":"Francesco Bonella ,&nbsp;Adriane DM Vorselaars ,&nbsp;Benjamin Wilde","doi":"10.1016/j.jaut.2024.103207","DOIUrl":"10.1016/j.jaut.2024.103207","url":null,"abstract":"<div><div>Renal involvement is a clinically relevant organ manifestation of sarcoidosis, leading to increased morbidity and complications. Although the exact incidence remains unknown, renal disease is likely to occur in up to one third of all sarcoidosis patients. Every patient with newly diagnosed sarcoidosis should receive a renal work-up and screening for disrupted calcium metabolism.</div><div>Amid various forms of glomerulonephritis, granulomatous interstitial nephritis is the most common one, but it rarely leads to renal impairment. Histologically, granulomas can be absent. Nephrocalcinosis and nephrolithiasis are frequent forms when hypercalcaemia or hypercalciuria occur. Drugs used for treatment of systemic sarcoidosis can also cause renal damage.</div><div>Due to its high heterogeneity, renal sarcoidosis can be difficult to treat. Glucocorticoids and various immunosuppressive treatments have been proven to be effective based on case series, but clinical trials are lacking. A treatment guideline for renal sarcoidosis is urgently needed.</div><div>In this review article, we present an overview of the different forms of renal sarcoidosis and the diagnostic steps to confirm renal involvement; in addition, we provide insights on the management and available treatments. A better understanding regarding the pathogenesis of sarcoidosis is the key for the development of more specific, targeted therapies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103207"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193881","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":"The immunopathogenesis of sarcoidosis","authors":"Jelle Miedema ,&nbsp;Francesco Cinetto ,&nbsp;Anna Smed-Sörensen ,&nbsp;Paolo Spagnolo","doi":"10.1016/j.jaut.2024.103247","DOIUrl":"10.1016/j.jaut.2024.103247","url":null,"abstract":"<div><div>Sarcoidosis is a granulomatous multiorgan disease, thought to result from exposure to yet unidentified antigens in genetically susceptible individuals. The exaggerated inflammatory response that leads to granuloma formation is highly complex and involves the innate and adaptive immune system. Consecutive immunological studies using advanced technology have increased our understanding of aberrantly activated immune cells, mediators and pathways that influence the formation, maintenance and resolution of granulomas. Over the years, it has become increasingly clear that disease immunopathogenesis can only be understood if the clinical heterogeneity of sarcoidosis is taken into consideration, along with the distribution of immune cells in peripheral blood and involved organs. Most studies offer an immunological snapshot during disease course, while the cellular composition of both the circulation and tissue microenvironment may change over time. Despite these challenges, novel insights on the role of the immune system are continuously published, thus bringing the field forward.</div><div>This review highlights current knowledge on the innate and adaptive immune responses involved in sarcoidosis pathogenesis, as well as the pathways involved in non-resolving disease and fibrosis development. Additionally, we describe proposed immunological mechanisms responsible for drug-induced sarcoid like reactions. Although many aspects of disease immunopathogenesis remain to be unraveled, the identification of crucial immune reactions in sarcoidosis may help identify new treatment targets. We therefore also discuss potential therapies and future strategies based on the latest immunological findings.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103247"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908762","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":"Unraveling the immunomodulatory impact of hydroxychloroquine on peripheral T cells using single-cell RNA sequencing.","authors":"Huizhong Long, Luis Espinosa, Amr H Sawalha","doi":"10.1016/j.jaut.2024.103324","DOIUrl":"10.1016/j.jaut.2024.103324","url":null,"abstract":"<p><p>Hydroxychloroquine (HCQ) is widely used in the treatment of a variety of autoimmune diseases. However, the mechanisms responsible for the immunomodulatory properties of HCQ in T cells remain unclear. Here we used single-cell RNA-sequencing to examine the effect of HCQ on T cells following in vitro stimulation. HCQ treatment led to a reduction in effector CD4⁺ T cells and upregulation of inhibitory genes including CTLA4 and TNFAIP3 in effector and naive CD4⁺ T cells, respectively. HCQ induced a significant expansion of effector CD8⁺ T cells, and significantly upregulated key cytotoxicity genes including GZMA, GZMB, GZMH, KLRD1, NKG7, and PRF1, as well as IFNG expression. Furthermore, HCQ treatment led to a reduction in the CD38⁺ CD8⁺ T cell subset, which is characterized by defective cytotoxicity and thought to both play a pathogenic role and increase susceptibility to infections in autoimmunity. We analyzed single-cell RNA-sequencing data in effector CD8⁺ T cells from lupus patients with or without HCQ treatment and confirmed upregulation of key cytotoxicity genes in patients receiving HCQ. In conclusion, this work provides additional insights into the immunomodulatory effects of HCQ and indicates that HCQ improves T cell cytotoxicity, which could explain a previously suggested protective effect of HCQ against infections in patients with autoimmune diseases.</p>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"103324"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466404","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":"Sarcoidosis and its relation to other immune-mediated diseases: Epidemiological insights","authors":"Elizabeth V. Arkema ,&nbsp;Marios Rossides ,&nbsp;Yvette C. Cozier","doi":"10.1016/j.jaut.2023.103127","DOIUrl":"10.1016/j.jaut.2023.103127","url":null,"abstract":"<div><div>Several epidemiological studies show a co-occurrence of sarcoidosis with other immune-mediated diseases (IMD). There are many similarities between sarcoidosis and IMDs in their geographical distribution and risk factors. Understanding these similarities and identifying the differences can help us to better understand sarcoidosis and put it into context with other IMDs. In this review, we present the current knowledge about the overlap between sarcoidosis and other IMDs derived from epidemiological studies. Epidemiologic methods utilize study design and statistical analysis to describe the patterns in data and, ideally, identify causal relationships between an exposure and a health outcome. We discuss how study design and analysis may affect the interpretation of epidemiological studies on this topic and highlight some theories that attempt to explain the relation between sarcoidosis and other IMDs.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103127"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41202114","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":"Application of laboratory models for sarcoidosis research","authors":"Maneesh Bhargava ,&nbsp;Elliott D. Crouser","doi":"10.1016/j.jaut.2024.103184","DOIUrl":"10.1016/j.jaut.2024.103184","url":null,"abstract":"<div><div>This manuscript will review the implications and applications of sarcoidosis models towards advancing our understanding of sarcoidosis disease mechanisms, identification of biomarkers, and preclinical testing of novel therapies. Emerging disease models and innovative research tools will also be considered.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103184"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039492","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":"Developmental drugs for sarcoidosis","authors":"Ogugua Ndili Obi ,&nbsp;Lesley Ann Saketkoo ,&nbsp;Lisa A. Maier ,&nbsp;Robert P. Baughman","doi":"10.1016/j.jaut.2024.103179","DOIUrl":"10.1016/j.jaut.2024.103179","url":null,"abstract":"<div><div><span>Sarcoidosis<span> is a multi-organ granulomatous </span></span>inflammatory disease<span> of unknown etiology. Over 50% of patients will require treatment at some point in their disease and 10%–30% will develop a chronic progressive disease with pulmonary fibrosis leading to significant morbidity and mortality.</span></div><div><span>Recently published guidelines recommend immunosuppressive therapy for sarcoidosis patients at risk of increased disease-related morbidity and mortality, and in whom disease has negatively impacted quality of life. </span>Prednisone the currently recommended first line therapy is associated with significant toxicity however none of the other guideline recommended steroid sparing therapy is approved by regulatory agencies for use in sarcoidosis, and data in support of their use is weak. For patients with severe refractory disease requiring prolonged therapy, treatment options are limited.</div><div>The need for expanding treatment options in sarcoidosis has been emphasized. Well conducted large, randomized trials evaluating currently available therapeutic options as well as novel pathways for targeting disease are necessary to better guide treatment decisions. These trials will not be without significant challenges. Sarcoidosis is a rare disease<span> with heterogenous presentation and variable progression and clinical outcome. There are no universally agreed upon biomarkers of disease activity and measurement of outcomes is confounded by the need to balance patient centric measures and objective measures of disease activity.</span></div><div>Our paper provides an update on developmental drugs in sarcoidosis and outlines several novel pathways that may be targeted for future drug development<span>. Currently available trials are highlighted and ongoing challenges to drug development and clinical trial design are briefly discussed.</span></div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103179"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318366","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":"PD-1 antibody interactions with Fc gamma receptors enable PD-1 agonism to inhibit T cell activation – therapeutic implications for autoimmunity","authors":"Yiqing Feng ,&nbsp;Gordafaried Deyanat-Yazdi ,&nbsp;Kristin Newburn ,&nbsp;Scott Potter ,&nbsp;Mark Wortinger ,&nbsp;Miriam Ramirez ,&nbsp;Stephanie M.E. Truhlar ,&nbsp;Pia P. Yachi","doi":"10.1016/j.jaut.2024.103339","DOIUrl":"10.1016/j.jaut.2024.103339","url":null,"abstract":"<div><div>PD-1 has emerged as a central inhibitory checkpoint receptor in maintaining immune homeostasis and as a target in cancer immunotherapies. However, targeting PD-1 for the treatment of autoimmune diseases has been more challenging. We recently showed in a phase 2a trial that PD-1 could be stimulated with the PD-1 agonist antibody peresolimab to treat rheumatoid arthritis. Here, we demonstrate that PD-1 antibodies can elicit agonism and inhibit T cell activation by co-localization of PD-1 with the T cell receptor via Fcγ receptor (FcγR) engagement. Three PD-1 agonist antibodies with different antigen binding domains, including the clinically validated PD-1 blocking antibody pembrolizumab, suppressed T cell activation to a similar degree; this finding suggests that a specific PD-1-binding epitope is not required for PD-1 agonism. We next explored whether antibody-mediated clustering was an important driver of inhibition of T cell activation; however, we found that a monovalent PD-1 antibody was not inferior to a conventional bivalent antibody in its ability to suppress T cell activation. Importantly, we found that affinity to PD-1 correlated positively with inhibition of T cell activation, with higher affinity antibodies exhibiting higher levels of inhibition. Using a series of human Fc mutants with altered affinities to various FcγRs, we dissected the contributions of FcγRs and found that multiple FcγRs rather than a single receptor contribute to agonist activity. Our work reveals an important role for FcγR binding in the activity of PD-1 antibodies, which has implications for optimizing both PD-1 agonist and antagonist antibodies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103339"},"PeriodicalIF":7.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721420","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":"Sunscreen use associated with elevated prevalence of anti-nuclear antibodies in U.S. adults","authors":"Christine G. Parks ,&nbsp;Todd A. Jusko ,&nbsp;Helen C.S. Meier ,&nbsp;Jesse Wilkerson ,&nbsp;Lisa G. Rider ,&nbsp;Frederick W. Miller ,&nbsp;Dale P. Sandler","doi":"10.1016/j.jaut.2024.103340","DOIUrl":"10.1016/j.jaut.2024.103340","url":null,"abstract":"<div><h3>Background</h3><div>Antinuclear antibody (ANA) prevalence in the U.S. population increased from 1988 to 2012, especially in white and more educated individuals. In adults ages 20–39 years from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and 2011–2012, ANA prevalence was previously associated with urinary concentrations of a common sunscreen ingredient, benzophenone 3, measured in winter. Spot urines may not capture relevant chronic exposures, thus we examined whether ANA was related to sunscreen use.</div></div><div><h3>Methods</h3><div>In a cross-sectional study of adults ages 20–59 (N = 416 ANA positive, 2656 ANA negative, by Hep-2 immunofluorescence, 1:80 dilution), we examined associations of ANA with reported sunscreen use when in the sun for 1 h or more. Logistic regression was used to calculate covariate-adjusted prevalence odds ratios (POR) and 95 % Confidence Intervals (CI), overall and stratified by demographic factors, season, and vitamin D. We explored associations and joint effects with other sun protective behaviors and sunburn in the past 12 months.</div></div><div><h3>Results</h3><div>The association of ANA with sunscreen differed by age (interaction p = 0.004): for ages 20–39, we saw an exposure response (POR 2.61, 95 % CI 1.50, 4.24 for using sunscreen always or most of the time, and POR 1.85; 1.12, 3.05 for less frequent versus never-use; trend p &lt; 0.001). These associations were more apparent in females (interaction p = 0.082), non-Hispanic white and black participants (vs. other race/ethnicity, interaction p = 0.023), and those with sufficient serum vitamin D (≥50 vs. &lt;50 nmol/L, interaction p = 0.001). ANA was not associated with other protective behaviors and not confounded or modified by these behaviors or recent sunburn.</div></div><div><h3>Conclusions</h3><div>These cross-sectional findings showed frequent sunscreen was associated with ANA in younger adults, supporting the need for replication, and longitudinal studies with detailed exposure histories.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103340"},"PeriodicalIF":7.9,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697349","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}