Evidence map›Paper›PMID 38946973›Full record

ArticlemedRxiv : the preprint server for health sciences2024

JAK inhibition decreases the autoimmune burden in Down syndrome.

Angela L Rachubinski, Elizabeth Wallace, Emily Gurnee, Belinda A Enriquez Estrada, Kayleigh R Worek, Keith P Smith, Paula Araya, Katherine A Waugh, Ross E Granrath, Eleanor Britton and 12 more

Registry-linked trialAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04246372 (Safety and Efficacy of Tofacitinib for Immune Skin Conditions in Down Syndrome), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT04246372 phase2completednot on this map

Safety and Efficacy of Tofacitinib for Immune Skin Conditions in Down Syndrome

TypeinterventionalSponsorUniversity of Colorado, DenverRan2020 to 2024Enrolled47ConditionsDown Syndrome, Alopecia Areata, Atopic Dermatitis / Eczema, Hidradenitis SuppurativaArmsTofacitinib
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Angela L RachubinskiLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Elizabeth WallaceDepartment of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Emily GurneeDepartment of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Belinda A Enriquez EstradaLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Kayleigh R WorekLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Keith P SmithLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Paula ArayaLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Katherine A WaughLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Ross E GranrathLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Eleanor BrittonLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Hannah R LyfordLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Micah G DonovanLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Neetha Paul EduthanLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Amanda A HillLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Barry MartinDepartment of Internal Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Kelly D SullivanLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID 0000-0003-2725-0205
Lina PatelLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Deborah J FidlerDepartment of Human Development and Family Studies, Colorado State University, Fort Collins, CO, 23 USA.
Matthew D GalbraithLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID 0000-0003-0485-3927
Cory A DunnickDepartment of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
David A NorrisDepartment of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Joaquin M EspinosaLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID 0000-0001-9048-1941

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Colorado Clinical and Translational Sciences Institute (CCTSI)UM1TR004399 · NCATS · UNIVERSITY OF COLORADO DENVER · PI JANINE A HIGGINS, RONALD J. SOKOL · 2023 to 2026
$30.7M
Training in Translational Research of Skin DiseasesT32AR007411 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI ASGARI, MARYAM MANDANA, ROOP, DENNIS · 1986 to 2025
$4.8M
Training Program in Cancer BiologyT32CA190216 · NCI · UNIVERSITY OF COLORADO DENVER · PI Craig T. Jordan · 2016 to 2026
$3.5M
Understanding Down Syndrome as an InterferonopathyR01AI150305 · NIAID · UNIVERSITY OF COLORADO DENVER · PI ESPINOSA, JOAQUIN M. · 2019 to 2020
$3.5M
JAK Inhibition in Down SyndromeR61AR077495 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI DUNNICK, CORY A, ESPINOSA, JOAQUIN M. · 2019 to 2021
$1.7M
NCATS NIH HHS UM1 TR004399NCI NIH HHS P30 CA046934NCI NIH HHS T32 CA190216NIAID NIH HHS R01 AI150305NIAMS NIH HHS R61 AR077495NIAMS NIH HHS T32 AR007411
6 · The paper itself

Abstract

Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmune disorders and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined. Here, we report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS. We demonstrate multi-organ autoimmunity of pediatric onset concurrent with unexpected autoantibody-phenotype associations. Importantly, constitutive immune remodeling and hypercytokinemia occur from an early age prior to autoimmune diagnoses or autoantibody production. We then report the interim analysis of a Phase II clinical trial investigating the safety and efficacy of the JAK inhibitor tofacitinib through multiple clinical and molecular endpoints. Analysis of the first 10 participants to complete the 16-week study shows a good safety profile and no serious adverse events. Treatment reduced skin pathology in alopecia areata, psoriasis, and atopic dermatitis, while decreasing interferon scores, cytokine scores, and levels of pathogenic autoantibodies without overt immune suppression. Additional research is needed to define the effects of JAK inhibition on the broader developmental and clinical hallmarks of DS. ClinicalTrials.gov identifier: NCT04246372.

Identifiers

PMID38946973
PMCPMC11213071

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Registered trials

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.