Microhemorrhage-related iron deposition in the tissues of patients with Systemic Sclerosis: a prospective study

Concept

Iron is an essential nutrient critical for many cellular processes, but its regulation is crucial to prevent harmful effects from either deficiency or excess. Labile iron (Fe(II)), a potent oxidant, can induce inflammation, cellular aging, and fibrosis by promoting the transformation of fibroblasts and endothelial cells into myofibroblasts, as observed in conditions like hemochromatosis. Experiments have shown that mice with iron overload can spontaneously develop fibrosis in organs such as the lungs, kidneys, and heart. However, the role of tissue iron in systemic sclerosis (SSc), a disease characterized by vascular damage, immune activation, and fibrosis, is not well understood. Early stages of SSc show microvascular damage and bleeding that could lead to significant iron deposition in tissues, considering that erythrocytes, which contain about 70% of the body's iron, are the source of the bleed. Preliminary studies have found evidence of labile iron in the skin of SSc patients, correlating with inflammatory and fibrotic gene expression, and MRI imaging has revealed iron deposits in the hands and hearts of SSc patients, even before visible fibrosis appears. The research aims to further explore how iron contributes to the fibrosis seen in SSc, using a combination of in vitro experiments, spatial phenotyping, and MRI T2* mapping to track iron in the body. Should this hypothesis prove true, iron chelators could represent a new therapeutic approach for managing early-stage SSc by targeting the fibrotic process.

Facts and figures

Project Lead
MD, PhD Nikolaos Vlachogiannis
National and Kapodistrian University of Athens Medical School
2024-2027
FOREUM research grant: € 200.000

Meet the Team

Project Lead

MD, PhD Nikolaos Vlachogiannis
National and Kapodistrian University of Athens Medical School
Theodora Kappi
Patient Research Partner
Katerina Koutsogianni
Patient Research Partner
Prof. Petros P. Sfikakis
National and Kapodistrian University of Athens

Objectives

  1. To in vitro examine the role of iron in proinflammatory/profibrotic transformation of cells.
  2. To ex vivo detect cellular ‘neighbourhoods’ with increased iron deposition and profibrotic transformation in the skin of SSc patients.
  3. To examine the diagnostic/prognostic value of iron quantification in vivo in the hands and internal organs of SSc patients.

Goals/Milestones

  1. Role of iron in profibrotic transformation of cells and preclinical value of iron chelators in fibrosis management.
  2. Advanced spatial phenotyping of SSc skin for the first time with special focus on iron-loaded regions.
  3. Development and validation of a new imaging analysis with prognostic value in SSc and comparison with capillaroscopy.

Patient Voice

Two PRPs have been recruited: 1) one SSc patient who has undergone the MRI protocol and has helped us refine the procedure, and 2) one board member of the Greek Patients’ Association and the RMD patient organization ‘ΡευΜΑζην’, who has helped us draft the lay summary of the project and plan outreach events to improve its visibility. Regular meetings with patients will be organized to better target their needs and expectations and to improve the visibility of the project. Our patients will continue to provide feedback to help us refine the MRI protocol and the protocol of the dermal biopsy and identify ways to improve their experience. Collaboration with our PRPs is also essential to help with the interpretation of results and dissemination of findings by tailoring key messages to patients and stakeholders such as the Greek Rheumatology Society and RMD patients’ organisations. We will participate in events and conferences organized by the patients’ organisations and will share our results in lay language through their newsletters and sites. We will also organize an open-science day annually to allow patients to visit the research facilities in our campus, interact with physicians and researchers and learn about the recent advances in personalized medicine. Through these direct and indirect interactions with patients we hope to establish an open-platform for communication to receive their feedback and to allow them to easily contact us with questions and ideas on further research in the field.

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