Evidence map›Paper›PMID 39896599›Full record

ArticlebioRxiv : the preprint server for biology2025

Autoantibody hotspots reveal origin and impact of immunogenic XIST ribonucleoprotein complex.

Bingyu Yan, Jinwoo Lee, Suhas Srinivasan, Quanming Shi, Diana R Dou, Srijana Davuluri, Swarna Nandyala, Adrianne Woods, Gwendolyn Leatherman, Yanding Zhao and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Bingyu YanDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0003-4429-8200
Jinwoo LeeDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Suhas SrinivasanDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Quanming ShiDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Diana R DouDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Srijana DavuluriDivision of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Swarna NandyalaDivision of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Adrianne WoodsDivision of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Gwendolyn LeathermanDivision of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yanding ZhaoDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Roman E ReggiardoDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Manasi SawantDepartments of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Hawa R ThiamDepartments of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Ami A ShahDivision of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
David F FiorentinoDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lorinda S ChungDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Howard Y ChangDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Funding

Sample Processing and Immunoassay Research CoreP30AR070254 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CLIFTON O BINGHAM, Antony Rosen · 2016 to 2026
$8.9M
Autoantibodies Define Scleroderma Subgroups with Distinct Relationships to CancerR01AR073208 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI LIVIA A CASCIOLA-ROSEN, Ami Aalok Shah · 2018 to 2026
$5.2M
Harnessing multivariate patient- and population-level disease trajectories to predict major clinical events in sclerodermaK24AR080217 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI Ami Aalok Shah · 2022 to 2026
$847k
"Lnc"ing XIST Ribonucleoprotein Particles to Female Sex-Attributed Biases in AutoimmunityK99AR080218 · NIAMS · STANFORD UNIVERSITY · PI DOU, DIANA REMY · 2022 to 2023
$211k
NIAMS NIH HHS K24 AR080217NIAMS NIH HHS K99 AR080218NIAMS NIH HHS P30 AR070254NIAMS NIH HHS R01 AR073208
6 · The paper itself

Abstract

Four out of five patients with autoimmune diseases are women. The XIST ribonucleoprotein (RNP) complex, comprising the female-specific long noncoding RNA XIST and over 100 associated proteins, may drive several autoimmune diseases that disproportionately affect women, who have elevated levels of autoantibodies against the XIST RNP. However, the structural distribution, potential origin, and clinical significance of XIST RNP autoantibodies remained unexplored. Here, we find that XIST RNP is associated with autoantigens associated with six female-biased autoimmune conditions. Mapping autoantibody targets to their occupancy sites on XIST shows that these autoantigens are concentrated at discrete "hotspots" along the XIST lncRNA, notably the A-repeat. Cell type-specific protein expression data nominated neutrophils as a predominant source of hotspot antigens, and we confirmed the presence of both XIST and hotspot antigens in neutrophil extracellular traps during NETosis, an immunogenic programmed cell death pathway triggered by neutrophil activation upon which neutrophils extrude their nuclear content. Furthermore, we found that levels of autoantibodies against a top hotspot antigen, SPEN, that binds the A-repeat, correlate with severe digital ischemia in systemic sclerosis in two independent cohorts. Together, these data show a plausible mechanism for the origin of AXA, guided by RNA structure and RNA-protein interactions, and show that antibodies to XIST RNP holds promise for disease endotyping and prognostication in femalebiased autoimmune conditions.

Identifiers

PMID39896599
PMCPMC11785099

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.