Evidence map›Paper›PMID 40274303›Full record

ArticleRMD open2025

Mitochondrial dysfunction and fatigue in Sjögren's disease.

Biji T Kurien, John Aubrey Ice, Rebecca A Wood, Gavin Pharaoh, Joshua Cavett, Valerie Lewis, Shylesh Bhaskaran, Astrid Rasmussen, Christopher J Lessard, A Darise Farris and 4 more

Abstract read
In one paragraph

Article in RMD open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Biji T Kurien *Research, US Department of Veterans Affairs, Oklahoma City, Oklahoma, USA.
John Aubrey Ice *Research, US Department of Veterans Affairs, Oklahoma City, Oklahoma, USA.ORCID 0000-0002-0066-9121
Rebecca A WoodArthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Gavin PharaohAging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Joshua CavettArthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Valerie LewisResearch, US Department of Veterans Affairs, Oklahoma City, Oklahoma, USA.
Shylesh BhaskaranAging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Astrid RasmussenGenes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.ORCID 0000-0001-7744-2948
Christopher J LessardPathology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.ORCID 0000-0003-2440-3843
A Darise FarrisArthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Kathy SivilisArthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Kristi A KoelschArthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Holly Van RemmenResearch, US Department of Veterans Affairs, Oklahoma City, Oklahoma, USA.
Robert Hal ScofieldResearch, US Department of Veterans Affairs, Oklahoma City, Oklahoma, USA robert.scofield@va.gov.

Funding

Pathogenic B Cells in Sjogren's SyndromeP50AR060804 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI SIVILS, KATHY L. · 2011 to 2015
$7.9M
GEROSCIENCE TRAINING PROGRAM IN OKLAHOMAT32AG052363 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Benjamin Francis Miller, William Edmund Sonntag · 2017 to 2026
$3.6M
Functional Evaluation of Established Sjogren's Syndrome Immune Response LociR01AR065953 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI LESSARD, CHRISTOPHER J · 2015 to 2018
$2.1M
Sjogren's Syndrome Pathogenic AutoantibodiesR01DE028001 · NIDCR · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SCOFIELD, ROBERT HAL · 2019 to 2023
$1.7M
Mitochondrial dysfunction, metabolic syndrome and oxidative damage in Sjogren's SyndromeR21DE026877 · NIDCR · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SCOFIELD, ROBERT HAL · 2017 to 2018
$361k
NIAMS NIH HHS P50 AR060804NIAMS NIH HHS R01 AR065953NIA NIH HHS T32 AG052363NIDCR NIH HHS R01 DE028001NIDCR NIH HHS R21 DE026877
6 · The paper itself

Abstract

objectiveSjögren's disease (SjD) is a chronic exocrine disorder typified by inflammation and dryness, but also profound fatigue, suggesting a pathological basis in cellular bioenergetics. In healthy states, dysfunctional mitochondria are recycled by mitophagic processes; when impaired, poorly functioning mitochondria persist and produce inflammatory reactive oxygen species. Employing a case-control study, we tested our hypothesis that mitochondrial dysregulation in T cells is associated with fatigue in SjD.

methodsWe isolated pan T cells from peripheral blood mononuclear cells of 13 SjD and 4 non-Sjögren's sicca (NSS) subjects, who completed several fatigue questionnaires, along with 8 healthy subjects. Using Seahorse, we analysed T cells for mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate, which we assessed for correlation with fatigue measures. Using public microarray data available for 190 SjD and 32 healthy subjects, we identified a mitophagic transcriptional signature that stratified SjD patients into 5 discrete clusters. Comparisons between the SjD subjects in these clusters to healthy individuals identified differentially expressed transcripts, which we subjected to bioinformatic interrogation.

resultsBasal OCR, ATP-linked respiration, maximal respiration and reserve capacity were significantly lower in SjD and NSS subjects compared with healthy individuals, with no differences in non-mitochondrial respiration, basal glycolysis or glycolytic reserve. Scores related to a sleep questionnaire and Bowman's Profile of Fatigue and Discomfort showed correlation with altered OCR in SjD. Subgroup differential expression analysis revealed dynamic transcriptional activity between mitophagy subgroups, expanding the number of differentially expressed transcripts tenfold.

conclusionsMitochondrial dysfunction and fatigue are significant problems in SjD warranting further investigation.

Indexed as

FatigueMitochondriaSjogren's SyndromeAdultAgedCase-Control StudiesEnergy MetabolismFemaleHumansLeukocytes, MononuclearMaleMiddle AgedOxygen ConsumptionT-LymphocytesAutoimmunityFatigueInflammationSjogren's SyndromeT-Lymphocytes

Identifiers

PMID40274303
PMCPMC12020762

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.