Unraveling the dark matter of infectious diseases, environmental and genetic factors tipping the balance towards NCDs, EU funded research, 2023-8

EU - Horizon Europe Grant - Medical University Vienna - Thomas Vogl - "Unraveling the dark matter of infectious diseases, environmental and genetic factors tipping the balance towards NCDs"*

I'd be interested to have @Jonathan Edwards take on this.

Also, Ron Davis has looked at HLA genes -

• NIH grant allocated 2018 (6 years ago) - anyone got a link to the published results?
• I assume Davis's [HLA] results were negative - if so then why look in the same place again?

*"
Objective
While it is known that post-COVID-19-condition (PCC) is caused by SARS-CoV-2 infection, for most other immune-related noncommunicable diseases (IR-NCDs), no such infectious disease (ID) triggers have been identified (yet). Many IDs exist that could potentially cause IR-NCDs, however these microbes have large genomes encoding many antigens possibly associated with IR-NCDs.

Given that it is challenging to measure all these 100,000s of structures in parallel, they represent the dark matter of ID-immune interactions. Furthermore, exposure to an ID alone typically does not trigger development of an IR-NCD: For example only a subset of patients infected with SARS-CoV-2 develop PCC. So, genetic- and environmental aspects also affect the onset of IR-NCDs, but the exact factors are unknown for most IR-NCDs.

Here, we aim to
1.) identify IDs triggering IR-NCDs by screening for antibody responses against 600,000 ID antigens, and
2.) to disentangle environmental and genetic factors affecting the transition from IDs to IR-NCDs.

We will combine novel multi-omics approaches and technologies for personalized genotyping of HLA and adaptive immune receptor genes to deeply profile 6,000 patients of six IR-NCDs (PCC, multiple sclerosis, ME/CFS, rheumatoid arthritis, lupus, IBD) to identify novel biomarkers and disease mechanisms. This project will represent the largest and most deeply profiled systematic study of multiple IR-NCDs with layered datasets allowing for comparative analyses yielding insights into shared mechanisms and potential differences in the role of IDs between IR-NCDs.

Building on associations identified from population scale and clinical cohorts, we will demonstrate causality in gnotobiotic mouse models, and leverage machine learning (ML) algorithms to predict disease progression and response to treatment. The combination of novel assays with ML represents a broadly applicable pipeline that can be used for studying the interplay of any other IDs/ IR-NCDs."
https://ec.europa.eu/info/funding-tenders/opportunities/portal/screen/opportunities/projects-details/43108390/101136582/HORIZON?isExactMatch=true&programmePeriod=2021 - 2027&frameworkProgramme=43108390&topicAbbreviation=HORIZON-HLTH-2023-DISEASE-03-07&order=DESC&pageNumber=1&pageSize=50&sortBy=title

 

It does not look to me as if they have much of a clue of immunopathology and mechanisms.
Why would antibodies to infectious agents tell us anything? And since people have been looking for antibodies like this for sixty years and found nothing more than a few red herrings I am doubtful that this will turn anything up.

They don't seem to realise that an IR-NCD does not need to be triggered by any infectious agent.

 

Thank you.

 

Yes, I seem to recall that Ron Davis et al (& Ian Lipkin - separately via NIH grant) looked at this years ago - people with a ME/CFS diagnosis had been exposed to pathogens but to a lesser extent than healthy people (who tend to pick up more infections since they're out and about)- nothing interesting was found. Perhaps they're looking for something like the EBV & MS link - but that seems a tad unlikely given previous studies.

 

Is this a newly accepted umbrella term for ME/CFS / LC / etc, or something else or older, or just another new acronym for the pile?

I try to keep up with these definitions or umbrella phrases and I get into trouble using them, for different reasons each time, so it is incredibly frustrating.

 

I have never heard of it and it has no merit. Another trendy garbage term to toss about at invited lectures and to work into grant proposals.

A septic ingrowing toenail is an immune mediated non-communicable disease.

 

That is unfortunate. I find that the accumulating mishmash of nonstandard definitions muddies the waters and damages our credibility as a field.