Research projects

The impact of mast cell activation on epithelial and endothelial barrier dysregulation in post-infectious ME/CFS (DegranulateME)

About

Status:

Ongoing

Principal investigator:

Eva Untersmayr-Elsenhuber

Country:

Austria

Study start:

2025-01

Completion (planned):

2025-12

Last update:

2024-12-10

Research types:

Basic research

Research areas:

Infections, Immune system dysfunction, Nutritional and metabolic system dysfunction, General

Interventions:

Biopsy

Priv. Sector Partner:

Not available

Sponsors:

WE&ME Foundation, Vienna Science and Technology Fund (WWTF)

Links

Project website

Project description

ME/CFS is a debilitating disease, with women being 2-3 times more often affected. Viral infections are considered the main triggers for ME/CFS, but the precise pathomechanisms remain unclear. The COVID-19 pandemic has provided new insights into post-infectious ME/CFS and a significant number of Post-COVID Syndrome (PCS) patients develop ME/CFS.

Mast cells, activated by viral triggers, release various inflammatory mediators, which contribute to inflammation and tissue damage by disrupting epithelial and endothelial barriers. Thus, mast cell activation (MCA) may trigger symptoms associated with the disease, such as cognitive impairment, pain and brain fog. Of interest, recent studies have shown that mast cells exhibit a stronger response and release of mediators upon activation in women. Unpublished data of our own research group show that post-infectious ME/CFS patients suffer from symptoms indicating MCA and respond to the treatment of MCA.

We suggest virally triggered mast cells to play a crucial role in the development of post-infectious ME/CFS. We hypothesise that MCA drives ME/CFS pathology via epithelial and endothelial barrier disruption. Our study will evaluate: (1) immune-related mast cell mediators and cell junction protein changes in post-infectious ME/CFS patients, (2) the proximety of viral fragments to activated mast cells in intestinal tissues, and (3) mast cell phenotype alterations in these patients. Utilising patient-derived samples, we will conduct in vitro co-culture models, examine MCA markers, and perform single-cell RNA sequencing to elucidate mast cell transcriptomic signatures.

The project DegranulateME aims to provide insights into the pathogenesis of post-infectious ME/CFS, emphasising the role of MCA in barrier integrity and inflammation. These insights are crucial for developing causative treatment approaches to restore barrier function and manage symptoms in post-infectious ME/CFS.

(Description adapted from project website: see link above)

Patient cohort

Not available.

Patients enrolled: Not available

Age group: Not available

Research areas

8

Research types

1

Research networks

0

Working groups

2

People

3

Publications

0

Organisations

2

Research areas

Viral infections

Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterised by a lack of independent metabolism and the inability to replicate outside living host cells. Descripton adapted from: https://www.ncbi.nlm.nih.gov/mesh/68014780.

Research projects:

14

Publications:

18

Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Description adapted from https://www.ncbi.nlm.nih.gov/mesh/68007239.

Research projects:

15

Publications:

20

Immune system dysfunction

Immune system is the body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Diseases of the immune system are disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-m...

Research projects:

Nutritional and metabolic system dysfunction

A collective term for nutritional disorders resulting from poor absorption or nutritional imbalance, and metabolic disorders resulting from defects in biosynthesis (anabolism) or breakdown (catabolism) of endogenous substances. Description adapted from: https://www.ncbi.nlm.nih.gov/mesh/68009750.

Research projects:

13

Publications:

16

General research that is not limited to a specific organ or body system dysfunction.

Research projects:

Transcriptomics

The determination of the pattern of genes expressed at the level of genetic transcription, under specific circumstances or in a specific cell. Description adapted from: https://www.ncbi.nlm.nih.gov/mesh/68020869.

Research projects:

7

Publications:

1

The systematic identification and quantitation of all the metabolic products of a cell, tissue, organ, or organism under varying conditions. The metabolome of a cell or organism is a dynamic collection of metabolites which represent its net response to current conditions. Description adapted from: https://www.ncbi.nlm.nih.gov/mesh/68055432...

Research projects:

Mast cell activation syndrome (MCAS)

A clinically and genetically heterogeneous group of mast cell disorders in which there is aberrant release of mast cell mediators with little to no accompanying proliferation of mast cells. Description adapted from: https://www.ncbi.nlm.nih.gov/mesh/2101194.

Research projects:

1

Publications:

3