Deciphering systemic and mucosal antibody repertoires against the microbiota in ME/CFS and PCC (CFSabs)

About

Status:

Ongoing

Principal investigator:

Thomas Vogl

Country:

Austria

Study start:

2025-01

Completion (planned):

2026-03

Last update:

2024-12-10

Research types:

Basic research

Research areas:

Immune system dysfunction, Digestive system dysfunction

Interventions:

Not applicable

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 an unclear etiology and pathogenesis. Similarities between ME/CFS and post-COVID-19 condition (PCC, also known as long COVID) have been observed. In both diseases, an involvement of the immune system and gut microbiota dysbiosis have been implicated in the pathophysiology. For example, using a high throughput antibody assay, the investigators have shown that ME/CFS patients mount antibody responses in blood against distinct gut microbiota. However, if such immune responses also exist in PCC, and how systemic antibodies are relevant to microbiota present at mucosal surfaces, remains largely unknown.

In the CFSabs project, the investigators will leverage exceptionally deeply profiled cohorts of ME/CFS and PCC patients assembled by Prof. Untersmayr-Elsenhuber, for which a breadth of biological samples (blood, stool, saliva, mRNA) are available. Immunoglobulin A (IgA)/Immunoglobulin G (IgG) from these samples (representing systemic exposures in blood, as well as mucosal ones from the gut and oral cavity) will be analysed for binding against 357,000 antigens using a proprietary, massively paralleled immune-assay (PhIP-Seq) available in Dr. Vogl’s lab. Additionally, mRNA levels of relevant immune barrier proteins in buccal epithelial cells of a sub-group of the cohort will be measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) to evaluate the oral immune barrier.

Analysing the convergence of systemic and mucosal responses may shed light on the diseases’ etiologies. Comparing immune signatures of ME/CFS vs PCC patients, as well as healthy controls, may also identify shared and divergent mechanisms as well as diagnostic markers. The results generated with the seed funding provided by this call, will then be leveraged to apply for follow up projects paving the way towards novel therapeutic and diagnostic approaches for both ME/CFS and PCC.

(Description adapted from project website: see link above)