Journal of Translational Autoimmunity最新文献

{"title":"Are serum C3 levels or kidney C3 deposits useful markers for predicting outcomes in patients with ANCA-associated vasculitis?","authors":"Alexis Cassard ,&nbsp;Clément Kounde ,&nbsp;Laurence Bouillet ,&nbsp;Tiphaine Goulenok ,&nbsp;David Ribes ,&nbsp;Rafik Mesbah ,&nbsp;Vincent Langlois ,&nbsp;Audrey Delas ,&nbsp;Françoise Fortenfant ,&nbsp;Sébastien Humbert ,&nbsp;Céline Lebas ,&nbsp;Julie Belliere ,&nbsp;Philippe Kerschen ,&nbsp;Dominique Chauveau ,&nbsp;Magali Colombat ,&nbsp;Stanislas Faguer","doi":"10.1016/j.jtauto.2023.100217","DOIUrl":"https://doi.org/10.1016/j.jtauto.2023.100217","url":null,"abstract":"<div><h3>Introduction</h3><p>Complement activation emerged as a key actor of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV). Whether serum levels of C3 (sC3) or C3 kidney deposition may help to refine the prognosis of AAV remains elusive.</p></div><div><h3>Methods</h3><p>Retrospective multicentric study that included 154 patients with a first flare of AAV and sC3 (n = 143) or C3 kidney staining (n = 95) available at diagnosis. Clinical presentations, kidney pathology, and survival of patients with normal or low sC3 were compared using univariate analyses, Kaplan-Maier curves with log-rank comparison, or multivariate Cox’ model, as appropriate.</p></div><div><h3>Results</h3><p>20 patients (14 %) had low sC3. sC3 (as bivariate low/normal or as a continuous variable) was associated with 5-year mortality but not with kidney survival. C3 kidney deposition (C3+) was identified in 23 patients who were characterized by more frequent chronic hypertension and lower eGFR at presentation (p = 0.04). C3+ correlated with IgG, IgM, C1q deposition (p = 0.07, p &lt; 0.0001 and p = 0.003, respectively). Chronicity and activity scores were similar in C3+ and C3- patients. Among C3+ patients, those with C3 deposition ≥2+ had lower eGFR at presentation (p = 0.006) and were more frequently classified as sclerotic using the Berden classification (p = 0.04) and as ‘high risk’ using the Brix score (p = 0.03). However, eGFR improvement following induction regimen was similar between C3+ and C3- patients, and kidney survival at 5 years was similar.</p></div><div><h3>Conclusions</h3><p>Correlation of sC3 with mortality confirms mechanistic links between complement pathways and AAV, but the lack of clear predictive sC3 cut-off and the similar kidney outcome irrespective of C3 deposition precludes their use as biomarkers of AAV outcomes and response to treatment.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100217"},"PeriodicalIF":3.9,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49858261","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":"Impact of COVID-19 and vaccination campaign on 1,755 systemic sclerosis patients during first three years of pandemic. Possible risks for individuals with impaired immunoreactivity to vaccine, ongoing immunomodulating treatments, and disease-related lung involvement during the next pandemic phase","authors":"Clodoveo Ferri ,&nbsp;Vincenzo Raimondo ,&nbsp;Dilia Giuggioli ,&nbsp;Laura Gragnani ,&nbsp;Serena Lorini ,&nbsp;Lorenzo Dagna ,&nbsp;Silvia Laura Bosello ,&nbsp;Rosario Foti ,&nbsp;Valeria Riccieri ,&nbsp;Serena Guiducci ,&nbsp;Giovanna Cuomo ,&nbsp;Antonio Tavoni ,&nbsp;Rossella De Angelis ,&nbsp;Fabio Cacciapaglia ,&nbsp;Elisabetta Zanatta ,&nbsp;Franco Cozzi ,&nbsp;Giuseppe Murdaca ,&nbsp;Ilaria Cavazzana ,&nbsp;Nicoletta Romeo ,&nbsp;Veronica Codullo ,&nbsp;Alessandro Antonelli","doi":"10.1016/j.jtauto.2023.100212","DOIUrl":"10.1016/j.jtauto.2023.100212","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;The impact of COVID-19 pandemic represents a serious challenge for ‘frail’ patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Patients and method&lt;/h3&gt;&lt;p&gt;This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p &lt; 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p &lt; 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p &lt; 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evaluated by comparing the COVID-19-related death rate recorded during pre- and post-vaccination pandemic periods, revealed a quite stable outcome in SSc patients &lt;em&gt;(&lt;/em&gt;death rate from 2.54 % to 1.76 %; p = ns), despite the significant drop of mortality observed in the Italian general population (from 2.95 % to 0.29 %; p &lt; 0.0001).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;An increased COVID-19 prevalence and mortality rate was recorded in SSc patients; moreover, the efficacy of vaccines in term of improved outcomes was less evident in SSc compared to Italian general population. This discrepancy might be explained by concomitant adverse prognostic factors: increased rate of non-responders to vaccine in SSc series, low percentage of individuals with four or more doses of vaccine, ongoing immunomodulating treatments, disease-related interstitial lung disease, and/or reduced preventive measures in the second half of pandemic. A c","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100212"},"PeriodicalIF":3.9,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a5/3d/main.PMC10580042.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49683130","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":"Metformin-induced activation of Ca2+ signaling prevents immune infiltration/pathology in Sjogren’s syndrome-prone mouse models","authors":"Viviane Nascimento Da Conceicao ,&nbsp;Yuyang Sun ,&nbsp;Xiufang Chai ,&nbsp;Julian L. Ambrus ,&nbsp;Bibhuti B. Mishra ,&nbsp;Brij B. Singh","doi":"10.1016/j.jtauto.2023.100210","DOIUrl":"https://doi.org/10.1016/j.jtauto.2023.100210","url":null,"abstract":"<div><p>Immune cell infiltration and glandular dysfunction are the hallmarks of autoimmune diseases such as primary Sjogren’s syndrome (pSS), however, the mechanism(s) is unknown. Our data show that metformin-treatment induces <em>Ca2+ signaling that restores saliva secretion and prevents immune cell infiltration in</em> the salivary glands of IL14α-transgenic mice (IL14α), which is a model for pSS. Mechanistically, we show that loss of <em>Ca2+ signaling is a major contributing factor, which is restored by metformin treatment,</em> in IL14α mice. Furthermore, the loss of <em>Ca2+ signaling leads to ER stress in salivary glands.</em> Finally, restoration of metformin-induced <em>Ca2+ signaling</em> inhibited the release of alarmins and prevented the activation of ER stress that was essential for immune cell infiltration. These results suggest that loss of metformin-mediated activation of <em>Ca2+</em> signaling prevents ER stress, which inhibited the release of alarmins that induces immune cell infiltration leading to salivary gland dysfunction observed in pSS.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100210"},"PeriodicalIF":3.9,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49858294","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":"Paradoxical psoriasis: The flip side of idiopathic psoriasis or an autocephalous reversible drug reaction?","authors":"Jiawei Lu,&nbsp;Yan Lu","doi":"10.1016/j.jtauto.2023.100211","DOIUrl":"10.1016/j.jtauto.2023.100211","url":null,"abstract":"<div><p>Psoriasis is a common, chronic skin disease that results mainly from the complex interplay between T cells, dendritic cells, and inflammatory cytokines including TNF-α, IL-17, IL-12, and IL-23. Successful therapy with anti-cytokine antibodies has proved the importance of these key cytokines, especially TNF-α. During the <em>anti</em>-TNF-α treatment of classical idiopathic psoriasis, a small portion of patients develop new psoriasiform lesions. This contradictory phenomenon was named paradoxical psoriasis which resembles idiopathic psoriasis clinically but presents overlapped histological patterns and distinct immunological processes. In this review, we discuss the differences between idiopathic psoriasis and paradoxical psoriasis with an emphasis on their innate immunity, as it is predominant in paradoxical psoriasis which exhibits type I IFN-mediated immunity without the activation of autoreactive T cells and memory T cells. We also put up an instructive algorithm for the management of paradoxical psoriasis. The decision on drug discontinuation or switching of biologics should be made based on the condition of underlying diseases and the severity of lesions.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100211"},"PeriodicalIF":3.9,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/49/main.PMC10507642.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41151299","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":"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}