Journal of Translational Autoimmunity最新文献

{"title":"Evaluation of a machine learning tool for the early identification of patients with undiagnosed psoriatic arthritis – A retrospective population-based study","authors":"J. Shapiro ,&nbsp;B. Getz ,&nbsp;S.B. Cohen ,&nbsp;Y. Jenudi ,&nbsp;D. Underberger ,&nbsp;M. Dreyfuss ,&nbsp;T.I. Ber ,&nbsp;S. Steinberg-Koch ,&nbsp;A. Ben-Tov ,&nbsp;Y. Shoenfeld ,&nbsp;O. Shovman","doi":"10.1016/j.jtauto.2023.100207","DOIUrl":"10.1016/j.jtauto.2023.100207","url":null,"abstract":"<div><h3>Background</h3><p>Psoriatic arthritis (PsA), an immune-mediated chronic inflammatory skin and joint disease, affects approximately 0.27% of the adult population, and 20% of patients with psoriasis. Up to 10% of psoriasis patients are estimated for having undiagnosed PsA. Early diagnosis and treatment can prevent irreversible joint damage, disability and deformity. Questionnaires for screening to identify undiagnosed PsA patients require patient and physician involvement.</p></div><div><h3>Objective</h3><p>To evaluate a proprietary machine learning tool (PredictAI™) developed for identification of undiagnosed PsA patients 1–4 years prior to the first time that they were suspected of having PsA (reference event).</p></div><div><h3>Methods</h3><p>This retrospective study analyzed data of the adult population from Maccabi Healthcare Service between 2008 and 2020. We created 2 cohorts: The general adult population (“GP Cohort”) including patients with and without psoriasis and the Psoriasis cohort (“PsO Cohort”) including psoriasis patients only. Each cohort was divided into two non-overlapping train and test sets. The PredictAI™ model was trained and evaluated with 3 years of data predating the reference event by at least one year. Receiver operating characteristic (ROC) analysis was used to investigate the performance of the model, built using gradient boosted trees, at different specificity levels.</p></div><div><h3>Results</h3><p>Overall, 2096 patients met the criteria for PsA. Undiagnosed PsA patients in the PsO cohort were identified with a specificity of 90% one and four years before the reference event, with a sensitivity of 51% and 38%, and a PPV of 36.1% and 29.6%, respectively. In the GP cohort and with a specificity of 99% and for the same time windows, the model achieved a sensitivity of 43% and 32% and a PPV of 10.6% and 8.1%, respectively.</p></div><div><h3>Conclusions</h3><p>The presented machine learning tool may aid in the early identification of undiagnosed PsA patients, and thereby promote earlier intervention and improve patient outcomes.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100207"},"PeriodicalIF":3.9,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10412462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9999254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation and immunomodulatory therapies influence the relationship between ATP-binding cassette A1 membrane transporter-mediated cholesterol efflux capacity and coronary atherosclerosis in rheumatoid arthritis","authors":"George A. Karpouzas ,&nbsp;Bianca Papotti ,&nbsp;Sarah R. Ormseth ,&nbsp;Marcella Palumbo ,&nbsp;Elizabeth Hernandez ,&nbsp;Maria Pia Adorni ,&nbsp;Francesca Zimetti ,&nbsp;Matthew J. Budoff ,&nbsp;Nicoletta Ronda","doi":"10.1016/j.jtauto.2023.100209","DOIUrl":"10.1016/j.jtauto.2023.100209","url":null,"abstract":"<div><h3>Objectives</h3><p>High-density lipoprotein (HDL) removes cholesterol from cells in atherosclerotic lesions, a function known as cholesterol efflux capacity (CEC). ATP-binding-cassette A1 (ABCA1) membrane transporter starts cholesterol transfer from macrophages to HDL particles. In rheumatoid arthritis (RA), methotrexate and biologic disease modifying drugs (bDMARDs) are atheroprotective whereas corticosteroids and C-reactive protein (CRP) are proatherogenic. We evaluated the influence of these factors on the relationship of ABCA1-CEC with atherosclerosis and cardiovascular events.</p></div><div><h3>Methods</h3><p>Atherosclerosis was evaluated with computed tomography angiography in 140 patients with RA and repeated in 99 after 6.9 ± 0.3 years. Events including acute coronary syndromes, stroke, cardiovascular death, claudication, revascularization, and heart failure were recorded. ABCA1-CEC was quantified in J774A.1 murine macrophages and reported as percentage of effluxed over intracellular cholesterol.</p></div><div><h3>Results</h3><p>Higher ABCA1-CEC associated with (i) more calcified plaques at baseline only in patients with CRP&gt;7 mg/L (median) (p-interaction = 0.001) and methotrexate nonusers (p-interaction = 0.037), and more partially-calcified plaques only in bDMARD nonusers (p-interaction = 0.029); (ii) fewer new calcified plaques in patients with below-median but not higher time-averaged CRP (p-interaction = 0.028); (iii) fewer new total and calcified plaques in prednisone unexposed but not patients exposed to prednisone during follow-up (p-interaction = 0.034 and 0.004) and (iv) more new plaques in baseline bDMARD nonusers and fewer in bDMARD users (p-interaction <span><math><mrow><mo>≤</mo></mrow></math></span> 0.001). Also, ABCA1-CEC associated with greater cardiovascular risk only in baseline prednisone users (p-interaction = 0.027).</p></div><div><h3>Conclusion</h3><p>ABCA1-CEC associated with decreased atherosclerosis in patients with below-median baseline and time-averaged CRP and bDMARD use. Conversely, ABCA1-CEC associated with increased plaque in those with higher CRP, corticosteroid users, methotrexate nonusers, and bDMARD nonusers. While in well-treated and controlled disease ABCA1-CEC appears atheroprotective, in uncontrolled RA its action may be masked or fail to counteract the inflammation-driven proatherogenic state.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100209"},"PeriodicalIF":3.9,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a8/70/main.PMC10371792.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9910511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrastructural skin alterations of healthy subjects with anti-desmoglein 1 antibodies in endemic areas to pemphigus foliaceus: A case series","authors":"Willy Ramos ,&nbsp;Nancy Rojas ,&nbsp;Alex G. Ortega-Loayza ,&nbsp;Mercedes Tello ,&nbsp;Gerardo Jiménez ,&nbsp;Nicolás Cuba-Cáceres ,&nbsp;Gerardo Ronceros ,&nbsp;Jhony A. De La Cruz-Vargas ,&nbsp;Víctor Juan Vera-Ponce ,&nbsp;Nadia Guerrero ,&nbsp;Ericson L. Gutierrez","doi":"10.1016/j.jtauto.2023.100208","DOIUrl":"https://doi.org/10.1016/j.jtauto.2023.100208","url":null,"abstract":"<div><h3>Background</h3><p>Endemic pemphigus foliaceus and endemic pemphigus vulgaris are autoimmune dermatologic disorders endemic to the Peruvian Amazon.</p></div><div><h3>Objective</h3><p>To determine the ultrastructural skin alterations of three healthy subjects with anti DSG-1 antibodies in areas endemic to pemphigus foliaceus and pemphigus vulgaris in the Peruvian Amazon.</p></div><div><h3>Patients and methods</h3><p>Case series carried out from data of three clinically healthy subjects positive to anti DSG-1 antibodies, from Peru. This study consists of a sub-analysis of data gathered in a previous study.</p></div><div><h3>Results</h3><p>Ultrastructural results are presented from the skin biopsies of three clinically healthy patients positive to <em>anti</em>-desmoglein 1 (DSG-1) antibodies. High Resolution Optical Microscopy (HROM) showed the absence of acantholysis. Transmission Electron Microscopy (TEM) showed the widening of intercellular space between keratinocytes, the presence of vacuoles in intercellular space with granular material and cytoplasmic vacuolization, loss of desmosome structure, loss of normal distribution among tonofilaments and lateral separation among cells in the stratum basale.</p></div><div><h3>Conclusion</h3><p>According to our results, healthy subjects that present <em>anti</em>-desmoglein 1 antibodies can develop ultrastructural alterations that are visible through transmission electron microscopy but not through conventional optical microscopy.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100208"},"PeriodicalIF":3.9,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49858263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statins influence the relationship between ATP-binding cassette A1 membrane transporter-mediated cholesterol efflux capacity and coronary atherosclerosis in rheumatoid arthritis","authors":"George A. Karpouzas ,&nbsp;Bianca Papotti ,&nbsp;Sarah R. Ormseth ,&nbsp;Marcella Palumbo ,&nbsp;Elizabeth Hernandez ,&nbsp;Maria Pia Adorni ,&nbsp;Francesca Zimetti ,&nbsp;Matthew J. Budoff ,&nbsp;Nicoletta Ronda","doi":"10.1016/j.jtauto.2023.100206","DOIUrl":"10.1016/j.jtauto.2023.100206","url":null,"abstract":"<div><h3>Objectives</h3><p>Cholesterol efflux capacity (CEC) is the main antiatherogenic function of high-density lipoprotein (HDL). ATP-binding-cassette A1 (ABCA1) membrane transporter initiates cholesterol export from arterial macrophages to pre-β HDL particles fostering their maturation; in turn, those accept cholesterol through ABCG1-mediated export. Impaired pre-β HDL maturation may disrupt the collaborative function of the two transporters and adversely affect atherosclerosis. Statins exert atheroprotective functions systemically and locally on plaque. We here evaluated associations between ABCA1-CEC, coronary atherosclerosis and cardiovascular risk and the influence of statins on those relationships in rheumatoid arthritis (RA).</p></div><div><h3>Methods</h3><p>Evaluation with computed tomography angiography was undertaken in 140 patients and repeated in 99 after 6.9 ± 0.3 years. Events comprising cardiovascular death, acute coronary syndromes, stroke, claudication, revascularization and heart failure were recorded. ABCA1-CEC and ABCG1-CEC were evaluated in J774A.1 macrophages and Chinese hamster ovary (CHO) cells respectively and expressed as percentage of effluxed over total intracellular cholesterol. Covariates in all cardiovascular event risk and plaque outcome models included atherosclerotic cardiovascular disease (ASCVD) risk score and high-density lipoprotein cholesterol.</p></div><div><h3>Results</h3><p>ABCA1-CEC negatively correlated with ABCG1-CEC (r = −0.167, p = 0.049). ABCA1-CEC associated with cardiovascular risk (adjusted hazard ratio 2.05 [95%CI 1.20–3.48] per standard deviation [SD] increment). There was an interaction of ABCA1-CEC with time-varying statin use (p = 0.038) such that current statin use inversely associated with risk only in patients with ABCA1-CEC below the upper tertile. ABCA1-CEC had no main effect on plaque or plaque progression; instead, ABCA1-CEC (per SD) associated with fewer baseline total plaques (adjusted rate ratio [aRR] 0.81, [95%CI 0.65–1.00]), noncalcified plaques (aRR 0.78 [95%CI 0.61–0.98]), and vulnerable low-attenuation plaques (aRR 0.41 [95%CI 0.23–0.74]) in statin users, and more low-attenuation plaques (aRR 1.91 [95%CI 1.18–3.08]) in nonusers (p-for-interaction = 0.018, 0.011, 0.025 and &lt; 0.001 respectively). Moreover, ABCA1-CEC (per SD) associated with greater partially/fully-calcified plaque progression (adjusted odds ratio 3.07 [95%CI 1.20–7.86]) only in patients not exposed to statins during follow-up (p-for-interaction = 0.009).</p></div><div><h3>Conclusion</h3><p>In patients with RA, higher ABCA1-CEC may reflect a proatherogenic state, associated with enhanced cardiovascular risk. Statin use may unmask the protective impact of ABCA1-mediated cholesterol efflux on plaque formation, progression and cardiovascular risk.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100206"},"PeriodicalIF":3.9,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/79/2e/main.PMC10362327.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9855548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of HLA-DRB1*04:01 on a mouse model of atherosclerosis","authors":"Garth Blackler ,&nbsp;James Akingbasote ,&nbsp;Ewa Cairns ,&nbsp;Christopher Howlett ,&nbsp;Patti Kiser ,&nbsp;Lillian Barra","doi":"10.1016/j.jtauto.2023.100203","DOIUrl":"10.1016/j.jtauto.2023.100203","url":null,"abstract":"<div><h3>Objectives</h3><p>HLA-DRB1 is associated with an increased risk of cardiovascular disease in patients with rheumatoid arthritis (RA). This study aimed to determine the effect of HLA-DRB1 on atherosclerotic cardiovascular disease (ASCVD) using a novel mouse model.</p></div><div><h3>Methods</h3><p>Mice transgenic for HLA-DRB1*04:01 (DR4tg) were crossed with low density lipoprotein receptor knock-out (<em>Ldlr</em>^{<em>−/−</em>}) mice that develop atherosclerosis when fed a high fat, high cholesterol (HFHC) diet. Male and female DR4tg<em>Ldlr</em>^{<em>−/−</em>} (n = 48), <em>Ldlr</em>^{<em>−/−</em>} (n = 24), DR4tg (n = 24), and C57Bl/6 (B6) background (n = 24) mice were fed HFHC or regular diet (RD) for 12 weeks. Blood samples were analyzed for serum lipoproteins using a colorimetric assay. C-reactive protein (CRP) and oxidized LDL (OxLDL) were measured using ELISA. Atherosclerosis in the aortas was assessed using the lipid stain, Sudan IV. The presence of citrulline in atherosclerotic plaque was determined by immunohistochemistry.</p></div><div><h3>Results</h3><p>Sera low-density lipoprotein cholesterol (LDL-C) levels were higher in HFHC-fed <em>Ldlr</em>^{<em>−/−</em>} versus DR4tg<em>Ldlr</em>^{<em>−/−</em>}<em>-</em>; p = 0.0056, but the aortic plaque burden and degree of citrullination in the plaque were similar for these two strains. The ratio of pro-atherogenic OxLDL to LDL levels was higher in DR4tg<em>Ldlr</em>^{<em>−/−</em>} than <em>Ldlr</em>^{<em>−/−</em>}mice; p = 0.0017. All mice had an increase in CRP when fed a HFHC diet, most pronounced for DR4tg<em>Ldlr</em>^{<em>−/−</em>}; p = 0.0009. There were no significant sex differences for DR4tg<em>Ldlr</em>^{<em>−/−</em>} mice; however, male <em>Ldlr</em>^{<em>−/−</em>} mice had worse atherosclerosis. B6 and DR4tg mice did not have significant elevations in serum cholesterol levels and did not develop atherosclerosis.</p></div><div><h3>Conclusions</h3><p>Expression of HLA-DRB1 resulted in an elevation of OxLDL and a reduction in the male bias for atherosclerosis, mimicking what is observed in RA.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100203"},"PeriodicalIF":3.9,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/96/main.PMC10318502.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9807276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPAR agonists for the treatment of primary biliary cholangitis: Old and new tales","authors":"Francesca Colapietro ,&nbsp;M. Eric Gershwin ,&nbsp;Ana Lleo","doi":"10.1016/j.jtauto.2023.100188","DOIUrl":"10.1016/j.jtauto.2023.100188","url":null,"abstract":"<div><h3>Introduction</h3><p>Primary biliary cholangitis (PBC) is an autoimmune liver disease involving the small intrahepatic bile ducts; when untreated or undertreated, it may evolve to liver fibrosis and cirrhosis. Ursodeoxycholic Acid (UDCA) is the standard of care treatment, Obeticholic Acid (OCA) has been approved as second-line therapy for those non responder or intolerant to UDCA. However, due to moderate rate of UDCA-non responders and to warnings recently issued against OCA use in patients with cirrhosis, further therapies are needed.</p><p><u>Areas covered.</u> Deep investigations into the pathogenesis of PBC is leading to proposal of new therapeutic agents, among which peroxisome proliferator-activated receptor (PPAR) ligands seem to be highly promising given the preliminary, positive results in Phase 2 and 3 trials. Bezafibrate, the most evaluated, is currently used in clinical practice in combination with UDCA in referral centers. We herein describe completed and ongoing trials involving PPAR agonists use in PBC, analyzing pits and falls.</p></div><div><h3>Expert opinion</h3><p>Testing new therapeutic opportunities in PBC is challenging due to its low prevalence and slow progression. However, new drugs including PPAR agonists, are currently under investigation and should be considered for at-risk PBC patients.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100188"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/6b/main.PMC9850184.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10579003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering live attenuated vaccines: Old dogs learning new tricks","authors":"Julia Plocica ,&nbsp;Fengguang Guo ,&nbsp;Jugal Kishore Das ,&nbsp;Koichi S. Kobayashi ,&nbsp;Thomas A. Ficht ,&nbsp;Robert C. Alaniz ,&nbsp;Jianxun Song ,&nbsp;Paul de Figueiredo","doi":"10.1016/j.jtauto.2023.100198","DOIUrl":"10.1016/j.jtauto.2023.100198","url":null,"abstract":"<div><p>Autoimmune diseases such as rheumatoid arthritis and type 1 diabetes are increasingly common global problems. Concerns about increases in the prevalence of such diseases and the limited efficacy of conventional treatment regimens necessitates new therapies to address these challenges. Autoimmune disease severity and dysbiosis are interconnected. Although probiotics have been established as a therapy to rebalance the microbiome and suppress autoimmune symptoms, these microbes tend to lack a number of advantageous qualities found in non-commensal bacteria. Through attenuation and genetic manipulation, these non-commensal bacteria have been engineered into recombinant forms that offer malleable platforms capable of addressing the immune imbalances found in RA and T1D. Such bacteria have been engineered to express valuable gene products known to suppress autoimmunity such as anti-inflammatory cytokines, autoantigens, and enzymes synthesizing microbial metabolites. This review will highlight current and emerging trends in the field and discuss how they may be used to prevent and control autoimmune diseases.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100198"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113845/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9741628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FRTX-02, a selective and potent inhibitor of DYRK1A, modulates inflammatory pathways in mouse models of psoriasis and atopic dermatitis","authors":"Soochan Kim ,&nbsp;Eunhwa Ko ,&nbsp;Hwan Geun Choi ,&nbsp;Daekwon Kim ,&nbsp;Monica Luchi ,&nbsp;Bernard Khor ,&nbsp;Sunghwan Kim","doi":"10.1016/j.jtauto.2022.100185","DOIUrl":"10.1016/j.jtauto.2022.100185","url":null,"abstract":"<div><p>Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) has been proposed as a novel regulator of adaptive immune homeostasis through modulating T cell polarization. Thus, DYRK1A could present a potential target in autoimmune disorders. Here, we identify FRTX-02 as a novel compound exhibiting potent and selective inhibition of DYRK1A. FRTX-02 induced transcriptional activity of the DYRK1A substrate NFAT in T cell lines. Correspondingly, FRTX-02 promoted ex vivo CD4⁺ polarization into anti-inflammatory Tregs and reduced their polarization into pro-inflammatory Th1 or Th17 cells. We show that FRTX-02 could also limit innate immune responses through negative regulation of the MyD88/IRAK4–NF-κB axis in a mast cell line. Finally, in mouse models of psoriasis and atopic dermatitis, both oral and topical formulations of FRTX-02 reduced inflammation and disease biomarkers in a dose-dependent manner. These results support further studies of DYRK1A inhibitors, including FRTX-02, as potential therapies for chronic inflammatory and autoimmune conditions.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100185"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/55/main.PMC9841288.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9114848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal mixture exposures and multiplexed autoantibody screening in Navajo communities exposed to uranium mine wastes","authors":"Esther Erdei ,&nbsp;Chris Shuey ,&nbsp;Curtis Miller ,&nbsp;Joseph Hoover ,&nbsp;Miranda Cajero ,&nbsp;Johnnye Lewis","doi":"10.1016/j.jtauto.2023.100201","DOIUrl":"10.1016/j.jtauto.2023.100201","url":null,"abstract":"<div><h3>Background</h3><p>Environmental exposures to metals in uranium mining wastes and drinking water were documented in more than half of the 1304 Navajo community members of the Diné Network for Environmental Health (DiNEH) Project, the first comprehensive assessment of exposures to these metals and community health on the Navajo Nation.</p></div><div><h3>Objective</h3><p>Evaluate environmental exposures among participants who provided blood and urine samples using multiplexed autoantibody positivity as an early effect biomarker.</p></div><div><h3>Methods</h3><p>Survey and geospatial location data, well water quality, and metals biomonitoring were used to assess exposures to mixed-metal wastes from 100 abandoned uranium waste sites.</p></div><div><h3>Results</h3><p>We observed that the prevalence of multiplexed autoantibody positivity in 239 participants was more than double that reported for the U.S. population (27.2% v. 13.8%) even though the national prevalence was generated using a different assay, the HEp-2 cell-based antinuclear antibody test. Increased risk of multiplexed autoantibody screening positivity (OR = 3.07,95%CI 1.15–8.22) was found among DiNEH study people who lived close to uranium mine and milling wastes and consumed metals in drinking water. Associations for females were even stronger when they lived closed to contaminated uranium mining and milling sites. <em>Anti</em>-U1-RNP antibodies were associated with water consumption of nickel.</p></div><div><h3>Conclusion</h3><p>Proximity to waste sites and consumption of metals in water even below current drinking water standards were associated with perturbations of immune tolerance. These findings are consistent with previous studies of autoimmunity in the local population and demonstrate that multiplexed autoantibody screening method has a potential as sentinel indicator of exposures to environmental metals.</p></div><div><h3>Impact statement</h3><p>This is the first, community-engaged environmental health study in exposed Navajo communities that applied clinical multiplexed testing in risk assessment of environmental metals associated with abandoned, unremediated uranium mining and milling waste sites. Routine clinical autoimmunity measures could be used as early effect biomarkers of environmental metal exposures.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100201"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/52/main.PMC10165442.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9446612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum autoantibodies and exploratory molecular pathways in rural miners: A pilot study","authors":"Esther Erdei ,&nbsp;Xixi Zhou ,&nbsp;Chris Shuey ,&nbsp;Nour Ass'ad ,&nbsp;Kimberly Page ,&nbsp;Bobbi Gore ,&nbsp;Chengsong Zhu ,&nbsp;Deborah Kanda ,&nbsp;Li Luo ,&nbsp;Akshay Sood ,&nbsp;Katherine E. Zychowski","doi":"10.1016/j.jtauto.2023.100197","DOIUrl":"10.1016/j.jtauto.2023.100197","url":null,"abstract":"<div><h3>Introduction</h3><p>The Southwestern United States (SWUS) has an extensive history of coal and metal mining, including uranium (U) mining. Lung diseases, including but not limited to, lung cancer and pulmonary fibrosis, have been studied extensively in miners due to occupational, dust-related exposures. However, high-throughput autoimmune biomarkers are largely understudied in miners, despite the fact that ore miners, such as U-miners, are at an increased risk for the development of autoimmune diseases such as systemic sclerosis and systemic lupus erythematosus (SLE). Additionally, there are current gaps in knowledge regarding which signaling pathways may play a role in occupational exposure-associated autoimmunity.</p></div><div><h3>Methods</h3><p>Most current and former miners in the SWUS live close to their previous workplaces, in remote areas, with limited access to healthcare. In this pilot study, by leveraging a mobile clinical platform for patient care and clinical outreach, we recruited 44 miners who self-identified as either U (n = 10) or non-U miners (n = 34) and received health screenings. Serum IgG and IgM autoantibodies against 128 antigens were assessed using a high-throughput molecular technique, as a preliminary health screening opportunity.</p></div><div><h3>Results</h3><p>Even when adjusting for age as a covariate, there was a significant (p &lt; 0.05) association between self-reported U-mining exposure and biomarkers including IgM alpha-actinin, histones H2B, and H4, myeloperoxidase (MPO) and myelin basic protein. However, adjusting for age did not result in significant associations for IgG autoantibody production in U-miners. Bioinformatic pathway analysis revealed several altered signaling pathways between IgM and IgG autoantibodies among both U and non-U miners.</p></div><div><h3>Conclusions</h3><p>Further research is warranted regarding the mechanistic connection between U-exposure and autoantibody development, especially regarding histone-related alterations and IgM autoantibody production.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100197"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/57/f8/main.PMC10023988.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9259337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}