Evidence map›Paper›PMID 37662351›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Inhibition of JAK-STAT pathway corrects salivary gland inflammation and interferon driven immune activation in Sjögren's Disease.

Sarthak Gupta, Eiko Yamada, Hiroyuki Nakamura, Paola Perez, Thomas J F Pranzatelli, Kalie Dominick, Shyh-Ing Jang, Mehdi Abed, Daniel Martin, Peter Burbelo and 15 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. 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, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 1 institution in 1 country.

Sarthak GuptaLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda MD, USA.
Eiko YamadaSalivary Disorder Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Hiroyuki NakamuraAdeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Paola PerezSalivary Disorder Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Thomas J F PranzatelliAdeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Kalie DominickSalivary Disorder Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Shyh-Ing JangSalivary Disorder Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Mehdi AbedSalivary Disorder Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Daniel MartinGenomics and Computational Biology Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Peter BurbeloGenomics and Computational Biology Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Changyu ZhengGenomics and Computational Biology Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Ben FrenchAdeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Ilias AlevizosSalivary Disorder Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Zohreh KhavandgarSalivary Disorder Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Margaret BeachNIDCR Sjögren's Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Eileen PelayoNIDCR Sjögren's Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Brian WalittNIDCR Sjögren's Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Sarfaraz HasniLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda MD, USA.
Mariana J KaplanLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda MD, USA.
Mayank TandonSalivary Disorder Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
M Teresa MagoneConsult Services Section, National Eye Institute, National Institutes of Health, Bethesda MD, USA.
David E KleinerLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
John A ChioriniAdeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Alan N BaerNIDCR Sjögren's Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Blake M WarnerSalivary Disorder Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
National Institutes of Health · US

Funding

Clinical Investigations Of Sjogren's SyndromeZ01DE000704 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI ILLEI, GABOR · 2002 to 2008
$3.0M
Intramural NIH HHS Z01 DE000704
6 · The paper itself

Abstract

Objectives: Inflammatory cytokines that signal through the JAK- STAT pathway, especially interferons (IFNs), are implicated in Sjögren's Disease (SjD). Although inhibition of JAKs is effective in other autoimmune diseases, a systematic investigation of IFN-JAK-STAT signaling and effect of JAK inhibitor (JAKi) therapy in SjD-affected human tissues has not been reported. Methods: Human minor salivary glands (MSGs) and peripheral blood mononuclear cells (PBMCs) were investigated using bulk or single cell (sc) RNA sequencing (RNAseq), immunofluorescence microscopy (IF), and flow cytometry. Results: RNAseq and IF showed activated JAK-STAT pathway in SjD MSGs. Elevated IFN-stimulated gene (ISGs) expression associated with clinical variables (e.g., focus scores, anti-SSA positivity). scRNAseq of MSGs exhibited cell-type specific upregulation of JAK-STAT and ISGs; PBMCs showed similar trends, including markedly upregulated ISGs in monocytes. Conclusions: SjD patients' tissues exhibit increased expression of ISGs and activation of the JAK-STAT pathway in a cell type-dependent manner. JAKi normalizes this aberrant signaling at the tissue level and in PBMCs, suggesting a putative viable therapy for SjD, targeting both glandular and extraglandular symptoms. Predicated on these data, a Phase Ib/IIa randomized controlled trial to treat SjD with tofacitinib was initiated.

Indexed as

InterferonJanus kinasesSjögren’s DiseaseSTATTofacitinib

Identifiers

PMID37662351
PMCPMC10473773
OpenAlexW4386023526

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

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.