Evidence map›Paper›PMID 36037362›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Novel antiinflammatory biologics shaped by parasite-host coevolution.

Stephanie M Ryan, Roland Ruscher, Wayne A Johnston, Darren A Pickering, Malcolm W Kennedy, Brian O Smith, Linda Jones, Geraldine Buitrago, Matt A Field, Adrian J Esterman and 13 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
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  6. Review
  7. Article
  8. Article
  9. A secreted fatty acid- and retinol- binding protein frombioRxiv : the preprint server for biology · 2025
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Infection and immunity · 2024
    Article
  15. Article
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  18. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 8 institutions in 5 countries.

Stephanie M RyanAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
Roland RuscherAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.ORCID 0000-0002-8600-6985
Wayne A JohnstonCommonwealth Scientific and Industrial Research Organisation-Queensland University of Technology Synthetic Biology Alliance, Australian Research Council Centre of Excellence in Synthetic Biology, Centre for Agriculture and the Bioeconomy, Centre for Genomics and Personalised Health, School of Biology and Environmental Science, Queensland University of Technology; Brisbane, QLD 4000, Australia.
Darren A PickeringAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.ORCID 0000-0002-7517-8773
Malcolm W KennedyInstitute of Biodiversity, Animal Health & Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom.ORCID 0000-0002-0970-5264
Brian O SmithInstitute of Molecular, Cell and Systems Biology, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom.ORCID 0000-0003-3363-4168
Linda JonesAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
Geraldine BuitragoAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
Matt A FieldAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.ORCID 0000-0003-0788-6513
Adrian J EstermanAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
Connor P McHughAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
Daniel J BrowneAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
Martha M CooperAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.ORCID 0000-0002-3758-6223
Rachael Y M RyanAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
Denise L DoolanAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.ORCID 0000-0001-7354-8817
Christian R EngwerdaDivision of Infectious Diseases, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Kim MilesAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
Makedonka MitrevaDivision of Infectious Diseases, Department of Medicine, Washington University in St, Louis, St. Louis, MO 63110.ORCID 0000-0001-9572-3436
John CroeseAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.ORCID 0000-0002-0718-3888
Tony RahmanDepartment of Gastroenterology and Hepatology, Prince Charles Hospital, Brisbane, QLD 4032, Australia.
Kirill AlexandrovCommonwealth Scientific and Industrial Research Organisation-Queensland University of Technology Synthetic Biology Alliance, Australian Research Council Centre of Excellence in Synthetic Biology, Centre for Agriculture and the Bioeconomy, Centre for Genomics and Personalised Health, School of Biology and Environmental Science, Queensland University of Technology; Brisbane, QLD 4000, Australia.
Paul R GiacominAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
Alex LoukasAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
Australian Institute of Tropical Health and Medicine · AUCommonwealth Scientific and Industrial Research Organisation · AUInstitute of Ecology and Biodiversity · CLPrince Charles Hospital · AUQIMR Berghofer Medical Research Institute · AUUniversity of Glasgow · GBUniversity of South Australia · AUWashington University in St. Louis · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Parasitic helminth infections, while a major cause of neglected tropical disease burden, negatively correlate with the incidence of immune-mediated inflammatory diseases such as inflammatory bowel diseases (IBD). To evade expulsion, helminths have developed sophisticated mechanisms to regulate their host's immune responses. Controlled experimental human helminth infections have been assessed clinically for treating inflammatory conditions; however, such a radical therapeutic modality has challenges. An alternative approach is to harness the immunomodulatory properties within the worm's excretory-secretory (ES) complement, its secretome. Here, we report a biologics discovery and validation pipeline to generate and screen in vivo a recombinant cell-free secretome library of helminth-derived immunomodulatory proteins. We successfully expressed 78 recombinant ES proteins from gastrointestinal hookworms and screened the crude in vitro translation reactions for anti-IBD properties in a mouse model of acute colitis. After statistical filtering and ranking, 20 proteins conferred significant protection against various parameters of colitis. Lead candidates from distinct protein families, including annexins, transthyretins, nematode-specific retinol-binding proteins, and SCP/TAPS were identified. Representative proteins were produced in mammalian cells and further validated, including ex vivo suppression of inflammatory cytokine secretion by T cells from IBD patient colon biopsies. Proteins identified herein offer promise as novel, safe, and mechanistically differentiated biologics for treating the globally increasing burden of inflammatory diseases.

Indexed as

Anti-Inflammatory AgentsBiological ProductsColitisHelminth ProteinsInflammatory Bowel DiseasesAnimalsHelminthsHumansMiceAnti-Inflammatory AgentsBiological ProductsHelminth ProteinshelminthhookwormIBDproteintherapeutic

Identifiers

PMID36037362
PMCPMC9457177
OpenAlexW4293483938

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.