Frontiers in lupus最新文献

{"title":"The 330 risk loci known for systemic lupus erythematosus (SLE): a review","authors":"Viktoryia Laurynenka, John B. Harley","doi":"10.3389/flupu.2024.1398035","DOIUrl":"https://doi.org/10.3389/flupu.2024.1398035","url":null,"abstract":"An in-depth literature review of up to 2023 reveals 330 risk loci found by genetic association at p ≤ 5 × 10−8, with systemic lupus erythematosus (SLE) in at least one study of 160 pertinent publications. There are 225 loci found in East Asian (EAS), 106 in European (EU), 11 in African-American (AA), 18 Mixed American (MA), and 1 in Egyptian ancestries. Unexpectedly, most of these associations are found to date at p ≤ 5 × 10−8 in a single ancestry. However, the EAS and EU share 40 risk loci that are independently established. The great majority of the identified loci [250 (75.8%) of 330] do not contain a variant that changes an amino acid sequence. Meanwhile, most overlap with known regulatory elements in the genome [266 (80.6%) of 330], suggesting a major role for gene regulation in the genetic mechanisms of SLE. To evaluate the pathways altered by SLE-associated variants, we generated gene sets potentially regulated by SLE loci that consist of the nearest genes, published attributions, and genes predicted by computational tools. The most useful insights, at present, suggest that SLE genetic mechanisms involve (1) the regulation of both adaptive and innate immune responses including immune cell activation and differentiation; (2) the regulation of production and response to cytokines, including type I interferon; (3) apoptosis; (4) the sensing and removal of immune complexes and apoptotic particles; and (5) immune response to infections, including Epstein–Barr Virus, and symbiont microorganisms. These mechanisms affected by SLE genes involve multiple cell types, including B cells/plasma cells, T cells, dendritic cells, monocytes/macrophages, natural killer cells, neutrophils, and endothelial cells. The genetics of SLE from GWAS data reveal an incredibly complex profusion of interrelated molecular processes and interacting cells participating in SLE pathogenesis, mostly unified in the molecular regulation of inflammatory responses. These genetic associations in lupus and affected molecular pathways not only give us an understanding of the disease pathogenesis but may also help in drug discoveries for SLE treatment.","PeriodicalId":94014,"journal":{"name":"Frontiers in lupus","volume":"4 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141099004","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":"Microfibrillar-associated protein 4 interaction with inflammation and clinical characteristics in neuropsychiatric systemic lupus erythematosus","authors":"Maria Alexandra Bandehkhoda Wegener, Sören Möller, M. Olesen, J. S. Madsen, G. Sørensen, Anne Voss, N. Asgari","doi":"10.3389/flupu.2024.1386256","DOIUrl":"https://doi.org/10.3389/flupu.2024.1386256","url":null,"abstract":"Central nervous system (CNS) proteins such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are released into the body fluids following CNS injury. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein. Recently we reported expression of MFAP4 in CNS and alteration of levels in patients with acute neuroinflammation. We aimed to determine the levels of MFAP4 in a predominantly population-based cohort of systemic lupus erythematosus (SLE) patients, including neuropsychiatric SLE (NPSLE), and to evaluate MFAP4 as a marker of inflammation.In total 208 SLE patients, 44 of those with NPSLE, and 50 age- and sex-matched healthy controls (HC) were recruited. MFAP4 was measured using AlphaLISA immunoassay. NfL, GFAP and a panel of inflammatory mediators were measured using Simoa HD-1 digital ELISA or a Luminex 200 instrument.MFAP4 levels were elevated in patients with NPSLE compared to patients with non-NPSLE (p = 0.031), more prominent in NPSLE patients with CNS involvement (p = 0.017). NfL and GFAP were higher in the total SLE cohort (p < 0.001, p < 0.001, respectively) as well as NPSLE subgroup (p < 0.001, p < 0.001, respectively), and in the subgroup of NPSLE patients with CNS involvement (p < 0.001, p < 0.001), compared to HC. NfL and GFAP levels correlated positively with MFAP4 in the NPSLE as well as the non-NPSLE subgroup (ρ = 0.44, p = 0.003, ρ = 0.25, p = 0.004). VEGF was reduced in NPSLE patients compared to HC (p = 0.015). MMP-9 was elevated in NPSLE compared to non-NPSLE (p = 0.048). Inflammatory markers including IFN-α, IL-6, IL-10 and TNF-α, were elevated in the NPSLE group compared to HC (p < 0.001, p = 0.0026, p = 0.042, p = 0.007, respectively). In NPSLE patients the levels of MFAP4 correlated with TNF-α (p = 0.016) and IL-17 (p = 0.0044) and with markers of blood brain barrier (BBB) disruption MMP-7 (p = 0.005) and VEGF (p < 0.001). In NPSLE patients with CNS manifestations MMP-3 and VEGF correlated with MFAP4 (p = 0.011, p = 0.0004, respectively).Levels of MFAP4 correlated with NfL, GFAP and proinflammatory cytokines and in NPSLE additionally with markers of BBB disruption, suggesting that MFAP4 is a marker of inflammation and vascular re-organization. Correlation of NfL and GFAP with MFAP4 may reflect CNS tissue damage.","PeriodicalId":94014,"journal":{"name":"Frontiers in lupus","volume":"98 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140978541","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":"Preterm birth, preeclampsia, gestational hypertension and offspring birth weight in women with active juvenile idiopathic arthritis and healthy controls","authors":"Carina Götestam Skorpen, S. Lydersen, Kjell Å. Salvesen, Marianne Wallenius","doi":"10.3389/flupu.2024.1375857","DOIUrl":"https://doi.org/10.3389/flupu.2024.1375857","url":null,"abstract":"There is insufficient knowledge about pregnancy outcomes in women with juvenile idiopathic arthritis (JIA). Our objective was to explore a possible association of inflammatory active JIA and pregnancy outcomes, including preterm birth, preeclampsia, gestational hypertension, and offspring gestational weight.We linked data from the Norwegian nationwide observational register RevNatus with data from the Medical Birth Registry of Norway (MBRN) for the period 2010 to 2019. Singleton births in women with JIA (n = 181) included in RevNatus were cases. After excluding births in mothers with rheumatic inflammatory diseases, the remaining singleton births registered in MBRN, served as population controls (n = 575 798).Preterm birth was more frequent in women with active JIA (17.6%) and of equivalent frequency in women with inactive JIA (3.1%), compared to population controls (4.9%). Preeclampsia had similar rates in women with JIA and population controls while gestational hypertension was more frequent in women with active JIA (7.2%) and inactive JIA (6.9%) compared to population controls (1.7%). Abnormal fetal growth occurred in similar rates in women with JIA and population controls.Having active JIA in pregnancy increased the risk for preterm birth (risk difference 12.7, 95% CI 4.7 to 25.3) and gestational hypertension (risk difference 6.2, 95% CI 1.4 to 16.8). There was no increased risk for preeclampsia or abnormal fetal growth compared to population controls.","PeriodicalId":94014,"journal":{"name":"Frontiers in lupus","volume":"59 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140742931","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":"Serum isolevuglandin IgG antibody concentrations are increased in patients with systemic lupus erythematosus and associated with lower 24-hour blood pressure","authors":"Anastasiia Phothisane, A. Oeser, Shahensha Shaik, Qiong Wu, Olivia Posey, Sean S. Davies, Jaya Krishnan, David M. Patrick, C. M. Stein, M. Ormseth","doi":"10.3389/flupu.2024.1377164","DOIUrl":"https://doi.org/10.3389/flupu.2024.1377164","url":null,"abstract":"Hypertension is frequent in patients with systemic lupus erythematosus (SLE) and is a major contributor to increased cardiovascular risk. Isolevuglandins (IsoLGs) are downstream products of oxidative stress that drive hypertension and SLE disease activity in animal models. Antibodies to IsoLGs (anti-IsoLGs) are present in human SLE and associated with disease activity, but it is not known if concentrations are higher compared to control subjects or if they are associated with blood pressure (BP).We measured serum anti-IsoLG IgG antibody concentrations by sandwich ELISA in 23 patients with SLE and 30 controls who had participated in a cross-sectional 24-hour ambulatory BP study. We examined the association between anti-IsoLG IgG antibodies and BP measurements in patients with SLE and controls by Spearman Rho (rs) and linear regression analysis.Serum anti-IsoLG IgG antibody concentrations were higher in patients with SLE than controls (P = 0.007) and inversely associated with BP in SLE but not controls. In patients with SLE antibody concentrations were inversely associated with office (rs = −0.418) and diurnal systolic BP (rs = −0.421); the relationship was stronger among patients not taking anti-hypertensives (office: rs = −0.740, diurnal systolic BP: rs = −0.802) and every 20% increase in antibody concentration was associated with 10 mmHg decrease in 24-hour systolic BP (P = 0.004).Serum anti-IsoLG IgG antibody concentrations are higher in patients with SLE than controls and are inversely associated with 24-hour BP measurements. Since IsoLGs promote hypertension, it is possible that in SLE, IsoLG antibodies could help clear these hypertension-inducing antigens.","PeriodicalId":94014,"journal":{"name":"Frontiers in lupus","volume":"120 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140378874","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":"Development of The Lupus Clinical Trials Enrollment Decision Aid: a pilot study","authors":"Leila Khalili, Rita Kukafka, Julia Weiner, Sean Inzerillo, Wei Tang, L. Geraldino-Pardilla, Nancyanne Schmidt, Yevgeniyia Gartshteyn, Kathleen Alvarez, A. Askanase","doi":"10.3389/flupu.2024.1373534","DOIUrl":"https://doi.org/10.3389/flupu.2024.1373534","url":null,"abstract":"In this pilot study, we describe the development of a patient-centered Decision Aid (DA) for participation of SLE clinical trials called “The Lupus Clinical Trials Enrollment DA”.A draft DA was designed by a development working group using a collaborative, iterative process using the International Patient Decision Aid Standards (IPDAS) guidelines. The approved draft DA was then pilot tested and refined using semi structured interview with 10 lupus providers and 12 SLE patients. Descriptive statistics were calculated. Interviews/surveys were conducted until thematic saturation was achieved. Responses on usefulness were accumulated, and mean usefulness scores were calculated. Feedback from the semi-structured interviews were categorized into several themes as outlined in the results section.The definition of treatments, side effects of each option, and expected improvement from each option was outlined. 90% of providers and 91.7% of patients reported that the definition of SOC treatment was clear. Additionally, the expected improvement for SOC (90% of providers, 100% of patients), clinical trial drug (70%, 91.6%), and placebo (70%, 100%) were noted to be clear. Side effects of SOC (80%, 100%), clinical trial drug treatment (80%, 100%), placebo (90%, 100%), were also noted to be clear. 100% of providers and patients thought that the figure outlining pros/cons of participating in clinical trials was appropriate. The mean usefulness scores for the DA were 4.45/5 for providers and 4.67/5 for patients.These data demonstrate that both patients and providers confirm that the newly developed The Lupus Clinical Trials Enrollment DA is useful and easy to use. Qualitative feedback from providers demonstrated concern that aspects of the DA, such as expected improvement and side effects might be unclear to patients; however, patients did not express the same concern in either the quantitative or qualitative feedback.","PeriodicalId":94014,"journal":{"name":"Frontiers in lupus","volume":" 49","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140221517","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":"A critical role for IFN-β signaling for IFN-κ induction in keratinocytes","authors":"Bin Xu, Jon Musai, Yee Sun Tan, G. Hile, W. Swindell, Benjamin Klein, J. T. Qin, M. Sarkar, J. Gudjonsson, J. M. Kahlenberg","doi":"10.3389/flupu.2024.1359714","DOIUrl":"https://doi.org/10.3389/flupu.2024.1359714","url":null,"abstract":"Cutaneous lupus erythematosus (CLE) affects up to 70% of patients with systemic lupus erythematosus (SLE), and type I interferons (IFNs) are important promoters of SLE and CLE. Our previous work identified IFN-kappa (IFN-κ), a keratinocyte-produced type I IFN, as upregulated in non-lesional and lesional lupus skin and as a critical regulator for enhanced UVB-mediated cell death in SLE keratinocytes. Importantly, the molecular mechanisms governing regulation of IFN-κ expression have been relatively unexplored. Thus, this study sought to identify critical regulators of IFN-κ and identified a novel role for IFN-beta (IFN-β).Human N/TERT keratinocytes were treated with the RNA mimic poly (I:C) or 50 mJ/cm2 ultraviolet B (UVB), followed by mRNA expression quantification by RT-qPCR in the presence or absence neutralizing antibody to the type I IFN receptor (IFNAR). IFNB and STAT1 knockout (KO) keratinocytes were generated using CRISPR/Cas9.Time courses of poly(I:C) and UVB treatment revealed a differential expression of IFNB, which was upregulated between 3 and 6 h and IFNK, which was upregulated 24 h after stimulation. Intriguingly, only IFNK expression was substantially abrogated by neutralizing antibodies to IFNAR, suggesting that IFNK upregulation required type I IFN signaling for induction. Indeed, deletion of IFNB abrogated IFNK expression. Further exploration confirmed a role for type I IFN-triggered STAT1 activation.Collectively, our work describes a novel mechanistic paradigm in keratinocytes in which initial IFN-κ induction in response to poly(I:C) and UVB is IFNβ1-dependent, thus describing IFNK as both an IFN gene and an interferon-stimulated gene.","PeriodicalId":94014,"journal":{"name":"Frontiers in lupus","volume":"40 11-12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140229326","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":"Insights into future management of lupus nephritis","authors":"A. Askanase, M. Dall'Era, S. Almaani","doi":"10.3389/flupu.2024.1334932","DOIUrl":"https://doi.org/10.3389/flupu.2024.1334932","url":null,"abstract":"Lupus nephritis (LN) is a common and serious manifestation of systemic lupus erythematosus and is a major cause of mortality and morbidity. The current standard-of-care treatment for LN include conventional immunosuppressive treatments such as mycophenolate mofetil, cyclophosphamide, or azathioprine, combined with glucocorticoids. However, this treatment approach has several unmet needs, such as achieving only modest remission rates, potential toxicities, and prolonged cumulative steroid exposure, resulting in suboptimal patient outcomes. The LN treatment landscape is evolving rapidly to meet these unmet needs, with belimumab and voclosporin being the first drugs approved specifically for treatment of LN in 2020 and 2021, respectively. Here, we review the likely roles in LN therapy for several targeted therapies, including select therapies under investigation, and interventions in early development such as therapies targeting B cells (obinutuzumab, atacicept, ianalumab, and CD19 chimeric antigen T-cell therapy), inflammatory cytokines (secukinumab and anifrolumab), and the immunoproteasome (zetomipzomib); we also review treatment strategies designed to minimize steroid exposure. Treatments in development have demonstrated encouraging short- and long-term efficacy and steroid-sparing potential, potentially paving the way for improved treatment regimens and patient outcomes in LN.","PeriodicalId":94014,"journal":{"name":"Frontiers in lupus","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139858503","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":"Insights into future management of lupus nephritis","authors":"A. Askanase, M. Dall'Era, S. Almaani","doi":"10.3389/flupu.2024.1334932","DOIUrl":"https://doi.org/10.3389/flupu.2024.1334932","url":null,"abstract":"Lupus nephritis (LN) is a common and serious manifestation of systemic lupus erythematosus and is a major cause of mortality and morbidity. The current standard-of-care treatment for LN include conventional immunosuppressive treatments such as mycophenolate mofetil, cyclophosphamide, or azathioprine, combined with glucocorticoids. However, this treatment approach has several unmet needs, such as achieving only modest remission rates, potential toxicities, and prolonged cumulative steroid exposure, resulting in suboptimal patient outcomes. The LN treatment landscape is evolving rapidly to meet these unmet needs, with belimumab and voclosporin being the first drugs approved specifically for treatment of LN in 2020 and 2021, respectively. Here, we review the likely roles in LN therapy for several targeted therapies, including select therapies under investigation, and interventions in early development such as therapies targeting B cells (obinutuzumab, atacicept, ianalumab, and CD19 chimeric antigen T-cell therapy), inflammatory cytokines (secukinumab and anifrolumab), and the immunoproteasome (zetomipzomib); we also review treatment strategies designed to minimize steroid exposure. Treatments in development have demonstrated encouraging short- and long-term efficacy and steroid-sparing potential, potentially paving the way for improved treatment regimens and patient outcomes in LN.","PeriodicalId":94014,"journal":{"name":"Frontiers in lupus","volume":"33 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139798393","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":"Osteonecrosis is associated with APOL1 variants in African Americans with systemic lupus erythematosus","authors":"Kevin Yip, Meredith Akerman, Ruth Fernandez Ruiz, Nicole Leung, Huda Algasas, Yingzhi Qian, Jill P. Buyon, Jasmin Divers, Peter Izmirly, Michael Belmont, Ashira D. Blazer","doi":"10.3389/flupu.2023.1219277","DOIUrl":"https://doi.org/10.3389/flupu.2023.1219277","url":null,"abstract":"Background/purpose African Americans (AA) with systemic lupus erythematosus (SLE) are at higher risk for both kidney disease and Osteonecrosis (ON). Two Apolipoprotein L1 (APOL1) risk variants (RV), G1 and G2, have been associated with chronic kidney disease (CKD), hypertension, and microvascular disease in AAs, which are independent risk factors for ON. Accordingly, we investigated the association between carriers of the APOL1 risk variants and the prevalence of ON in AA SLE patients. Methods A cohort of 121 adult participants of self-reported AA ancestry and meeting at least four of the American College of Rheumatology (ACR) revised criteria for SLE were recruited from a high volume urban SLE clinical site. PCR/sequencing was used to stratify participants by APOL1 genotype. Medical records, including clinical notes and imaging reports, were retrospectively reviewed for documentation of ON. Association between the number of APOL1 risk variants with time to first ON was tested. Results In our cohort, 18 individuals developed ON; across the APOL1 genotype groups, 2/37 0RV, 11/59 1RV, and 5/15 2RV participants were affected. The mean time to ON was 27 years, 22 years, and 18 years in 0RV, 1RV, and 2RV carriers, respectively. An adjusted Cox regression model showed that carrying the APOL1 risk variants associated with shorter ON free survival with hazard ratios (HR) of 3.1 (95% CI: 1.6–6.2) and 9.6 (95% CI 2.4–37.8) for 1RV and 2RV carriers, respectively. 2RV carriers more often exhibited multiple and bilateral joint sites affected by ON. Disease duration was longer in ON-affected participants at 20.5 years compared to 9.0 years in those unaffected ( p &amp;lt; 0.001). In individuals who had received glucocorticoids, median cumulative prednisone equivalent dose was higher in ON-affected participants, though this did not reach statistical significance (18.7 g vs. 9.0 g; p -value = 0.3). Conclusion Our analysis suggests a higher risk of osteonecrosis among African American SLE patients who carry the APOL1 risk variants. In addition, disease duration increased the rate of ON. Given the high frequency of the APOL1 risk variants in African Americans, APOL1 high-risk genotype carriers may represent an ON-vulnerable subgroup within the AA population. Further work is necessary to uncover the mechanism of this association.","PeriodicalId":94014,"journal":{"name":"Frontiers in lupus","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135095382","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":"Increased carotid intima–media thickening and antioxidized low-density lipoprotein in an anti-Ro60 SLE autoantibody subset","authors":"Biji T. Kurien, James Fesmire, Swapan K. Nath, R. Hal Scofield","doi":"10.3389/flupu.2023.1197309","DOIUrl":"https://doi.org/10.3389/flupu.2023.1197309","url":null,"abstract":"Objective Premature atherosclerosis is associated with systemic lupus erythematosus (SLE). We have previously shown an association of anti-Ro60/La/Ro52 with antioxidized low-density lipoprotein (LDL) in SLE. Here, we hypothesized that carotid intima–media thickening (CIMT) would be associated with antioxidized LDL (anti-oxLDL)/antilipoprotein lipase (ALPL) in a specific SLE autoantibody subset (anti-Ro60 positive, anti-RNP positive, anti-SmRNP positive, or extractable nuclear antigen antibody negative). Methods We carried out a case-control study (one time-point testing) of CIMT, ALPL, anti-oxLDL, anti-low density lipoprotein (ALDL), and anti-LDL in 114 SLE patients and 117 age/sex-matched controls. The levels of total cholesterol, LDL, high-density lipoprotein (HDL), triglycerides, and HDL-Trig were also measured. A student's t -test was used for statistical analysis. Results Interestingly, the level of CIMT was highest in the SLE subset with anti-Ro60 (23/114). CIMT and anti-oxLDL were statistically significantly elevated in the anti-Ro60 SLE subset (1.3 ± 1.66, p &amp;lt; 0.01; 0.26 ± 0.16, p &amp;lt; 0.002, respectively) compared with controls (0.54 ± 1.26; 0.165 ± 0.13, respectively), but not anti-LPL/anti-LDL. CIMT was significantly elevated (0.9 ± 1.71; p &amp;lt; 0.05) in the SLE subset without antiextractable nuclear antigen (ENA) (63/114) compared with controls. The other antibodies in this subset were not statistically different from other SLE subsets or controls. Only antioxLDL was significantly elevated (0.29 ± 0.27; p &amp;lt; 0.005) in the SLE subset with anti-RNP (14/114) compared with controls, while none were elevated in the anti-SmRNP subset (6/114). We did not find any significant differences in lipids between the various SLE subsets. Conclusion CIMT segregates in anti-Ro and ENA negative groups either with or without anti-oxLDL. It will be clinically important if cardiovascular events are augmented in the SLE anti-Ro subset having elevated antioxidized LDL antibodies.","PeriodicalId":94014,"journal":{"name":"Frontiers in lupus","volume":"93 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135719045","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}