Evidence map›Paper›PMID 41968960›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2026

PEPITEM Regulates the Synovial Microenvironment During Immune-Mediated Inflammatory Arthritis to Limit Disease.

Mussarat Wahid, Samuel Kemble, Oladimeji Abudu, Anella Saviano, Christopher Mahony, Jonathan W Lewis, Thomas A Nicholson, Anna Schettino, Noemi Marigliano, Kathryn Frost and 25 more

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In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2026. 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

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors.

Mussarat WahidRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Samuel KembleRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Oladimeji AbuduRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Anella SavianoImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Christopher MahonyRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.ORCID https://orcid.org/0000-0003-4487-2540
Jonathan W LewisRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Thomas A NicholsonRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Anna SchettinoImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Noemi MariglianoImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Kathryn FrostRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Jenefa BegumDepartment of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
Alyssa M UrbanowskiRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Marion LimoNanoscale and Microscale Research Centre, University of Nottingham, Nottingham, UK.
Rakesh JhaNanoscale and Microscale Research Centre, University of Nottingham, Nottingham, UK.
Sandra Martinez JarquinNanoscale and Microscale Research Centre, University of Nottingham, Nottingham, UK.ORCID https://orcid.org/0000-0002-4908-8934
Laleh PezhmanDepartment of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
Abbie E A DeganTranslational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK.
Amy E AndersonTranslational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK.
Charlotte G SmithRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Armaiti BatkiRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Holly AdamsRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Francesco CasoRheumatology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.ORCID https://orcid.org/0000-0002-8928-2520
Raffaele ScarpaRheumatology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Iain McInnesSchool of Infection & Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.ORCID https://orcid.org/0000-0003-4449-8501
Stefan SiebertSchool of Infection & Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.ORCID https://orcid.org/0000-0002-1802-7311
Arthur G PrattTranslational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK.
Andrew FilerRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Karim RazaRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Adam P CroftRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.ORCID https://orcid.org/0000-0002-9487-0511
Myriam ChimenRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Felicity de CoganNanoscale and Microscale Research Centre, University of Nottingham, Nottingham, UK.
G Ed RaingerDepartment of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
Asif J IqbalDepartment of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
Francesco MaioneImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Helen M McGettrickRheumatology Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, UK.ORCID https://orcid.org/0000-0002-5950-8840

Funding

AORN A. Cardarelli Scholarship n. 725/2022 GRC- Linea Progettuale 1.3: "GestionBritish Society for Research on Ageing - Chernajovsky Foundation Ph.D. Scholarship. PhD StudentshipKennedy Trust for Rheumatology Research KENN 19-20-06Medical Research Council MR/T028025/1RTD-A research CN00000041University of Naples Federico II PhD scholarship PNRR DM 118 M4C1- INV 4.1 ricerca PNRR genericiWellcome Leap Dynamic Resilience program (co-funded by Temasek Trust). TJ
6 · The paper itself

Abstract

objectiveHere we investigate the status of the adiponectin-PEPITEM pathway in early, treatment naive rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and the therapeutic efficacy of PEPITEM administration in preclinical models.

methodsPeripheral blood was isolated from patients with clinical suspect arthralgia and suspected inflammatory arthritis and analyzed by flow cytometry or Western blot. Effect of PEPITEM treatment on inflammatory arthritis was assessed in mice by histology, single-cell RNA sequencing, flow cytometry, or multiplex analysis.

resultsPatients newly diagnosed with RA and PsA had significantly reduced expression of adiponectin receptor 2 and its downstream signaling adapter protein APPL-1 on their peripheral-blood mononuclear cells, resulting in diminished response to adiponectin and local synovial concentrations of PEPITEM. Building on these observations, treatment with PEPITEM in three distinct inflammatory arthritis animal models significantly reduced arthritis severity, joint swelling, leukocyte infiltration, and expression of several pro-inflammatory mediators (eg, JE [CCL2], RANTES, interleukin-16) in the synovium. Mechanistically, PEPITEM treatment suppressed the cyclooxygenase 2 and NF-κB signaling pathways. Moreover, PEPITEM altered the composition of leukocyte subsets recruited into the joint.

conclusionCollectively, these findings underscore the importance of understanding the dysregulation of the adiponectin-PEPITEM pathway in different immune-mediated inflammatory diseases (IMIDs), such as RA and PsA. The observed differences in expression and downstream signaling through adiponectin receptors suggest potential targets for therapeutic intervention to restore the balance of this regulatory pathway to mitigate chronic inflammation and disease progression in these patients, paving the way for its clinical use as an alternative and/or combination therapy for early IMIDs.

Indexed as

Arthritis, PsoriaticArthritis, RheumatoidCellular MicroenvironmentSynovial MembraneAdiponectinAnimalsArthritis, ExperimentalCyclooxygenase 2Disease Models, AnimalFemaleHumansMaleMiceNF-kappa BReceptors, AdiponectinSignal TransductionAdiponectinCyclooxygenase 2NF-kappa BReceptors, Adiponectin

Identifiers

PMID41968960
PMCPMC13313099

What Socratic holds

Textmetadata
LicenceCC BY
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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.