bioRxiv : the preprint server for biology最新文献

{"title":"A DNA Typewriter records the cell lineage history of a mouse, from zygote to late organogenesis.","authors":"Qi Yu, Haedong Kim, Sophie Seidel, James F Acosta-Clark, Beth K Martin, Kyle O'Connor, Riza M Daza, Molly Gasperini, Jenny F Nathans, Maggie Lam, Elena Gamo, Shruthi VijayKumar, Lauren Kuo, Jean-Benoît Lalanne, Kamen P Simeonov, Marion Pepper, Cole Trapnell, Jesse M Gray, Junhong Choi, Chengxiang Qiu, Jay Shendure","doi":"10.64898/2026.07.29.741625","DOIUrl":"10.64898/2026.07.29.741625","url":null,"abstract":"<p><p>Mammalian biology unfolds over time, within tissues and organs opaque to our eyes and instruments. We applied DNA Typewriter, a sequential molecular recorder, to record the cell lineage of a mouse over nearly two weeks of development. From one embryo, we reconstruct a time-calibrated, parsimony-supported, zygote-rooted phylogeny of 1.28M transcriptionally-profiled cells. A burst of editing unequivocally marks the daughters of the first cleavage, which serve as inline replicates. We quantify clonal dominance arising during gastrulation. Tree siblings share cell type far above chance; heterotypic siblings mark terminal differentiations. Temporal sweeps of clade co-occurrence recover a dated hierarchy of cell-type couplings; imputed labels for internal nodes recapitulate known state paths. A lineage-anchored ontogeny of mammalian development, long out of reach, is coming into view.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148804502","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":"Unmasking Early Hepatorenal Fibrosis in Polycystic Kidney Disease Using Noninvasive Precision Molecular MRI of Collagen.","authors":"Oluwabukola S Bamishaye, Francis Akinlotan, Phillip H Chumley, Jingjuan Qiao, Xiu Chen, Farzaneh Dorabadizare, Roye Ronald, Annye Bennett, Mandy J Croyle, Khan Hekmatyar, Alton B Farris, Anna G Sorace, Harrison Kim, Jian-Xiong Wang, Hans E Grossniklaus, Bradley K Yoder, Michal Mrug, Jenny J Yang","doi":"10.64898/2026.07.19.739445","DOIUrl":"10.64898/2026.07.19.739445","url":null,"abstract":"<p><p>Fibrosis begins early in autosomal dominant polycystic kidney disease (ADPKD) and drives its progression. Collagen deposition has been observed to increase around cysts in human ADPKD kidneys and livers. Currently, no clinical methods are available to detect early fibrosis before irreversible structural and functional decline. Here, we report fibrosis imaging using Gd-hProCA32.Collagen, a collagen-targeting protein MRI contrast agent for precision molecular MRI (pMRI). Gd-hProCA32.Collagen binds collagen type I with micromolar affinity, exhibiting higher relaxivity than clinical agents at 1.4 T, blood clearance within 72 hours, and no evident acute toxicity. To assess the ability of Gd-hProCA32.Collagen to detect ADPKD-related fibrosis, renal collagen deposition was increased by 11 weeks of age in <i>Pkhd1</i> ^PCK/PCK (PCK) rats. At 26 weeks, Gd-hProCA32.Collagen, given at a 10-fold lower dose than gadobutrol, produced sustained kidney and liver enhancement through 48 hours, whereas enhancement washed out in wild-type organs and with a non-targeted control protein. Gd-hProCA32.Collagen also increased the number of detected renal cysts per animal by 25% compared with 3% for gadobutrol (<i>P</i> < 0.0001), mainly small and medium cysts outlined by pericystic collagen, and revealed striation-like enhancement at microcyst clusters. Regional enhancement correlated with histological collagen (<i>r</i> = 0.72), whereas gadobutrol enhancement did not (<i>r</i> = 0.21). Kidney and liver enhancement was also observed in a <i>Pkd2</i> mutant mouse model. These findings reveal a previously inaccessible subclinical fibrotic phase of polycystic kidney and liver disease and support collagen-targeted pMRI for noninvasive detection and mapping of fibrosis when conventional biomarkers remain uninformative.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13419732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650372","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":"A chemically modified promoter-targeted duplex RNA activates <i>TCF4</i> expression.","authors":"Bethany A Janowski, Victor Tse, Jiaxin Hu, Sarah A Cobb, Khayden Dong, David R Corey","doi":"10.64898/2026.10.02.756310","DOIUrl":"https://doi.org/10.64898/2026.10.02.756310","url":null,"abstract":"<p><p>Pitt-Hopkins syndrome (PTHS) is a severe neurodevelopmental disorder caused by haploinsufficient expression of transcription factor 4 ( <i>TCF4</i> ). Increasing expression from the remaining functional <i>TCF4</i> allele could provide a mutation-independent strategy for patients with diverse pathogenic variants. We integrated genomic datasets with strand-specific RNA analysis to identify transcribed regions of the <i>TCF4</i> promoter suitable for targeting by activating double-stranded RNAs (dsRNAs). Screening of overlapping promoter-targeted dsRNAs identified a hotspot for increased <i>TCF4</i> expression. Activation was retained by a lead dsRNA containing extensive 2'-fluoro, 2'-O-methyl, and phosphorothioate modifications used in therapeutic oligonucleotides. Anti-AGO2 immunoprecipitation showed association with RNA transcribed from the targeted promoter region. dsRNA-mediated activation was associated with increased RNA polymerase II occupancy. These findings establish promoter-targeted dsRNAs as chemically tractable starting points for increasing <i>TCF4</i> expression and support their investigation as a mutation-independent strategy for haploinsufficient disease.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170714","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":"PWK genetic background reprograms heterochromatin and malignant epithelial states in Neu-driven mammary tumors.","authors":"Rui Geng, Ryann R Ray, Jennifer B Jacob, Benjamin L Kidder","doi":"10.64898/2026.10.01.755936","DOIUrl":"10.64898/2026.10.01.755936","url":null,"abstract":"<p><p>Genetic background can alter the latency and behavior of cancers initiated by the same oncogenic driver, but how inherited variation reshapes the regulatory landscape that permits tumor development remains poorly understood. The PWK genetic background accelerates mammary tumor onset in the NeuT model. We compared PWK NeuT and BALB NeuT tumors using tumor-level RNA-seq, histone ChIP-seq, and single-cell multiome profiling. PWK tumors exhibited broad transcriptional reprogramming characterized by reduced immune-associated expression and increased epithelial differentiation and neuronal-like programs. Chromatin remodeling was spatially redistributed rather than uniformly increased or decreased. PWK tumors showed expansion of H3K9me3- and H4K20me3-associated chromatin, while both marks were depleted across many expressed genes and concentrated within selected intergenic and repeat-rich territories, revealing coordinated redistribution of constitutive heterochromatin. Single-cell multiome profiling showed that broad epithelial representation remained similar between strains, yet specific malignant states were strongly strain biased. Integrated RNA and accessibility analyses identified concordant strain-selective regulatory programs and candidate loci, while trajectory analysis revealed distinct epithelial state transitions between PWK NeuT and BALB NeuT tumors. Together, these findings indicate that inherited genetic background reshapes transcriptional programs, heterochromatin organization, and malignant epithelial state trajectories in NeuT mammary tumors, providing a regulatory framework for understanding strain-dependent differences in tumor onset.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167317","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":"Community-wide adaptive evolution of gut bacteria during dietary transitions.","authors":"Samantha G Hernandez, Siddharth Uppal, Dong-Min Jin, Abigail A Landers, Nathaniel Ennis, Daniel D Sprockett, Andrew H Moeller","doi":"10.64898/2026.10.01.755998","DOIUrl":"10.64898/2026.10.01.755998","url":null,"abstract":"<p><p>Diet exerts selection on bacterial species within the mammalian gut microbiota^1,2,3,4,5, but the extent, modes, genomic bases, and repeatability of gut bacterial adaptive evolution in response to dietary variation within hosts are poorly understood. Here, we show that within-host dietary transitions drive ubiquitous and highly reproducible adaptive evolution of gut bacterial populations. We deeply profiled allele-frequency dynamics in gut microbiota of an experimental cohort of litter-matched wild-derived isogenic mice either transitioned from low-fat/highcarbohydrate diets to high-fat/low-carbohydrate diets or maintained on their ancestral lowfat/high-carbohydrate diet. Dietary transitions induced significantly parallel allele-frequency changes across replicates in 61/62 core gut bacterial species within five months, whereas 0/62 species displayed significant across-replicate parallelism in the control group, indicating deterministic adaptive evolutionary responses across the gut microbiota. Adaptation proceeded through multiple modes, including strain sorting and gene-wise responses. The latter were enriched in a subset of gene families and functions across bacterial species, including invertases. Culturing revealed an invertible DNA switch in <i>Phocaeicola sartorii</i> that, in all replicates transitioned to high-fat/low-carbohydrate diets, localized a promoter sequence upstream of cell-surface glycan foraging genes. These findings elucidate widespread gut bacterial adaptive evolution mediated by within-host dietary variation.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171260","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":"Comparison of sodium azide- and cooling-based immobilization methods for <i>Caenorhabditis elegans</i> chemotaxis assays.","authors":"Rachel Ji, Shawndra Wibisono, Jingru Sun","doi":"10.64898/2026.09.28.755163","DOIUrl":"https://doi.org/10.64898/2026.09.28.755163","url":null,"abstract":"<p><p>Chemotaxis assays are widely used to quantify sensory-driven behavioral responses in <i>Caenorhabditis elegans</i> . Sodium azide is commonly used to immobilize animals at assay endpoints, although concerns have been raised that diffusion beyond the endpoint region could affect behavior before a choice is completed. We compared sodium azide-mediated immobilization with post-assay cooling using the repellent 1-octanol and attractant diacetyl. Wild-type animals showed robust avoidance of 30% 1-octanol and attraction to 0.5% diacetyl with either method, across multiple assay durations, and with or without worm food <i>Escherichia coli</i> OP50. These results support post-assay cooling as an alternative endpoint-scoring method.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171254","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":"A regenerative fibroblast competence field supports multiple cell fates in adult skin regeneration.","authors":"Chih-Han Huang, Chih-Kuan Chen, Chen Yuan Kam, Ben Van Handel, Arijita Sarkar, Yen-Chun Ho, Denis Evseenko, Cheng-Ming Chuong, Hans I-Chen Harn","doi":"10.64898/2026.10.01.756129","DOIUrl":"10.64898/2026.10.01.756129","url":null,"abstract":"<p><p>Adult mammalian wounds typically restore tissue integrity through fibrotic repair rather than regeneration of the original architecture. Here, we compared small non-regenerative and large regenerative skin wounds to investigate how fibroblasts acquire regenerative competence and enter alternative cell-fate programs. Integrated single-cell RNA sequencing identified a transient signaling and extracellular-matrix-remodeling niche enriched in large wounds, together with NCAM1-associated competent fibroblast states. Time-resolved analysis positioned these states within a root-like fibroblast manifold connected to hair dermal-condensate, endothelial, pericyte and glial-associated fate-entry programs. Inferred cell-cell communication networks revealed shared matrix and adhesion signals, superimposed with branch-associated inputs, including VEGF signaling toward NCAM1-positive endothelial-transition cells. Lineage tracing showed that PDGFRA- and NCAM1-expressing lineages contributed to vascular- and nerve/glial-associated regenerative compartments. Functionally, partial NCAM1 perturbation reduced vascular organization while increasing hair follicle neogenesis, whereas stronger inhibition impaired both outcomes. These findings identify NCAM1 as a regulator of regenerative competence and fate specification within a regenerative competence field rather than a marker of a single terminal lineage. We propose that regenerative wounds activate an NCAM1-associated fibroblast competence field whose quantitative modulation biases competent fibroblasts toward alternative outcomes.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168463","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":"Streamlined Production of Recombinant Adeno-Associated Viruses Using Gateway Cloning Technology for Neural Circuit All-Optical Interrogation.","authors":"Annick Ayon, Abdelali Jalil, Coailinn Egan, Bertrand Ducos, Caroline Mailhes-Hamon, Astou Tangara, Benjamin Mathieu, Alexis-Pierre Bemelmans, Isabel Llano, Laurent Bourdieu, Stéphane Dieudonné, Vincent Villette, Jonathan Bradley","doi":"10.64898/2026.09.22.752944","DOIUrl":"10.64898/2026.09.22.752944","url":null,"abstract":"<p><p>The advent of optogenetics and the rapid development of genetically encoded actuators and reporters for calcium, voltage, neurotransmitters, and other molecules have revolutionized neuroscience research by enabling precise, non-invasive optical interrogation of neural circuits. Successful implementation, however, critically depends on efficient reporter expression in defined neuronal populations. We present a Gateway®-based cloning platform providing a robust pipeline for rapid, efficient construction of recombinant adeno-associated virus (rAAV) vectors optimized for neuroscience applications. This platform addresses promoter selection, indicator engineering, and capsid-type optimization, and enables systematic optimization of vector components across a range of optical tools. The benefit of this modular approach is illustrated in the case of ULoVE, a two-photon microscopy method based on acousto-optic deflectors (AODs). This method provides serial light-targeting with kHz sampling rates and high signal-to-noise ratio in vivo, which imposes stringent requirements on indicator expression - including cell-type specificity, sparse labelling, and precise control of expression levels- efficiently met through the combinatorial flexibility of the Gateway pipeline. As specific examples, Gateway-constructed Cre-driver viruses combined with Cre-dependent reporters enabled cell-type-specific labelling for two complementary applications. In cerebellar Purkinje cells, an L7::Cre driver virus paired with a Gateway-constructed voltage indicator (JEDI2P-Kv) and ULoVE two-photon excitation at ~5 kHz enables resolution of sub-millisecond dendritic voltage dynamics in awake, behaving mice, including optical detection of dendritic spikelets previously accessible only via intracellular electrophysiology. The same driver virus paired with calcium indicators (GCaMP6f, jRGECO1a) resolves climbing fiber-evoked calcium kinetics under the same conditions. In acute cerebellar slices, a kit::Cre driver virus enabled cell-type-specific expression of the optogenetic actuator ChR2(H134R) in molecular layer interneurons, where ULoVE doughnut-pattern photostimulation achieved single-cell, sub-millisecond optogenetic activation with micron-scale spatial resolution. Beyond ULoVE applications, the same sparse, strong labelling also proved suitable for anatomical tracing of axonal projections in cleared cerebellar tissue, resolving individual DCN axon terminals at the granule cell layer-molecular layer boundary. Taken together, our dual-front approach-combining a modular AAV expression pipeline with AOD-based optical acquisition-provides an integrated platform for developing sophisticated optical tools, including but not limited to AOD-based microscopy, for neural circuit interrogation.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13622121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122314","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 Alzheimer's Disease-associated gene CD2AP regulates permeability of endothelial cells and transendothelial migration of immune cells.","authors":"Michael D Onken, John A Cooper","doi":"10.64898/2026.10.01.755982","DOIUrl":"10.64898/2026.10.01.755982","url":null,"abstract":"<p><p>Variants at the CD2AP locus, which encodes a branched-actin regulator, are associated with late-onset Alzheimer's disease (AD), and CD2AP-deficient mice show increased blood-brain barrier (BBB) permeability. CD2AP is enriched in endothelial cells, but its function there is poorly understood. In endothelium, branched actin networks maintain cell-cell junctions and are also required for immune cells to cross through individual endothelial cells (transcellular transendothelial migration, TEM). We previously showed that the Arp2/3 activators N-WASP and WAVE2 contribute to these processes, but the capping protein (CP)-interacting proteins involved are unknown. Here we tested whether CD2AP, a CP-interacting protein recruited to cell-cell contacts, regulates both junction integrity and TEM. In primary human microvascular endothelial cells, shRNA knockdown of CD2AP increased TNFα-induced monolayer permeability, measured by transendothelial electrical resistance, and altered VE-cadherin junction morphology. Unexpectedly, on soft hydrogels the same knockdown reduced TEM of NK-92 MI cells, lowering the proportion of transcellular events. Thus, loss of CD2AP weakens the endothelial barrier yet impairs a distinct, actin-dependent route of immune-cell passage. These findings suggest that CD2AP risk variants may affect the BBB through more than permeability, and they identify endothelial immune-cell trafficking as a testable link between CD2AP and AD.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167906","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":"Longitudinal linear-epitope profiling of SLE identifies novel antigens associated with disease and disease activity.","authors":"Charlotte Hurabielle, Yutong V Wang, Bryan Castillo-Rojas, Chung-Yu Wang, Colette Caspar, James Asaki, Monica Dayao, Max Calcoen, Eric D Merrill, Aaron Bodansky, Arielle Klepper, Elizabeth N Chung, Caroline Vissers, Kelsey C Zorn, Mark S Anderson, Michael R Wilson, Peter Izmirly, Jill Buyon, Jinoos Yazdany, Maria Dall'Era, Chun J Ye, Joseph L DeRisi","doi":"10.64898/2026.09.29.755420","DOIUrl":"https://doi.org/10.64898/2026.09.29.755420","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is characterized by diverse autoantibodies, yet established biomarkers capture only a fraction of autoreactivity. We profiled 1,268 plasma samples from 695 patients with SLE and 301 healthy controls using phage immunoprecipitation sequencing (PhIP-seq). Machine learning identified a reproducible autoreactivity signature that discriminated SLE from controls across two validation cohorts. SLE autoreactivities were enriched for RNA-binding proteins, while targets containing Basic Acidic Dipeptide repeat domains were associated with high disease activity. A YTHDF2-derived peptide was the most prevalent shared autoreactivity, occurring in ∼25% of patients and exhibiting sequence similarity to Epstein-Barr virus (EBV) lytic switch protein BZLF1. Competition assays demonstrated higher-affinity binding to the viral peptide, consistent with EBV-associated molecular mimicry. Orthogonal validation using a 10-peptide Luminex panel strongly discriminated SLE from healthy controls. These findings expand the SLE autoantibody landscape, identify disease activity associated autoreactivities and insight linking EBV-driven immunity to epitope-specific autoimmunity in lupus.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168227","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}