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

PEPITEM Modulates the Synovial Environment in Immune-Mediated Inflammatory Arthritis to Mitigate Disease Progression

  • By

  • Mussarat Wahid

  • Samuel Kemble

  • Oladimeji Abudu

  • Anella Saviano

  • Christopher Mahony

  • Jonathan W. Lewis

  • Thomas A. Nicholson

  • Anna Schettino

  • Noemi Marigliano

  • Kathryn Frost

  • Jenefa Begum

  • Alyssa M. Urbanowski

  • Marion Limo

  • Rakesh Jha

  • Sandra Martinez Jarquin

  • Laleh Pezhman

  • Abbie E. A. Degan

  • Amy E. Anderson

  • Charlotte G. Smith

  • Armaiti Batki

  • Holly Adams

  • Francesco Caso

  • Raffaele Scarpa

  • Iain McInnes

  • Stefan Siebert

  • Arthur G. Pratt

  • Andrew Filer

  • Karim Raza

  • Adam P. Croft

  • Myriam Chimen

  • Felicity de Cogan

  • G. Ed Rainger

  • Asif J. Iqbal

  • Francesco Maione

  • Helen M. McGettrick

  • July 1, 2026

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Objective:

To explore the changes in the adiponectin–PEPITEM pathway in patients with inflammatory arthritis and investigate the therapeutic efficacy of PEPITEM in murine models of inflammatory arthritis, particularly in relation to disease progression.

Approach:
  • Human Samples: Whole blood was obtained from consenting patients with suspected inflammatory arthritis and healthy donors. Patients were classified based on established criteria for RA and PsA.
  • Isolation of PBMCs: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and stored for further analysis.
  • Migration Assay: Treg cells were treated with PEPITEM and assessed for their ability to migrate across inflamed endothelial cells.
  • T Cell Polarization: PBMCs were isolated and CD4+ T cells were enriched for polarization studies.
Key Findings:
  • PEPITEM levels are diminished in patients with immune-mediated inflammatory diseases, indicating a potential role in disease pathology.
  • Supplementation of PEPITEM can limit leukocyte migration and reduce disease severity in murine models of inflammatory arthritis.
  • Patients with RA have elevated levels of adiponectin, which correlates with increased disease severity.
Interpretation:

The study indicates that PEPITEM replacement therapy may have potential as a treatment for patients with RA and PsA by restoring regulatory pathways.

Limitations:
  • The study primarily focuses on murine models, which may not fully replicate the complexities of human disease.
  • The effects of different isoforms of adiponectin on PEPITEM secretion and their implications for therapy remain unclear.
Conclusion:

PEPITEM may play a crucial role in modulating inflammation and disease progression in inflammatory arthritis.

Original Source(s)

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

  • by Mussarat Wahid, Samuel Kemble, Oladimeji Abudu, Anella Saviano, Christopher Mahony, Jonathan W. Lewis, Thomas A. Nicholson, Anna Schettino, Noemi Marigliano, Kathryn Frost, Jenefa Begum, Alyssa M. Urbanowski, Marion Limo, Rakesh Jha, Sandra Martinez Jarquin, Laleh Pezhman, Abbie E. A. Degan, Amy E. Anderson, Charlotte G. Smith, Armaiti Batki, Holly Adams, Francesco Caso, Raffaele Scarpa, Iain McInnes, Stefan Siebert, Arthur G. Pratt, Andrew Filer, Karim Raza, Adam P. Croft, Myriam Chimen, Felicity de Cogan, G. Ed Rainger, Asif J. Iqbal, Francesco Maione, Helen M. McGettrick

  • July 1, 2026

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