Publication highlights June 2024

These are just some selected articles to highlight from a wealth of recent publications citing the use of Olink’s PEA technology.

A 15-protein signature accurately discriminates MIS-C from sepsis

In a study from Patel and colleagues at Western University in Canada, the Olink® Explore 3072 platform for high-multiplex proteomics was used to select biomarkers that identify a rare but serious complication of SARS-CoV-2 infection in children.

In the diagnosis of Multi-System Inflammatory Syndrome in Children (MIS-C), it is important to quickly discriminate this condition from symptomatically overlapping cases of SARS-CoV-2 negative sepsis (SCNS) so that the correct treatment can be initiated as early as possible. Comparison of the expression of ~3,000 proteins in plasma from children with MIS-C and SCNS revealed 58 markers associated with MIS-C. Advanced machine learning methods were then applied to derive an extremely high-performance 15-protein model that discriminated MIS-C from SCNS with an AUC=1.00. Bioinformatic analysis of the 58 proteins showed that all organ systems were represented with greatest enrichment in the digestive tract, emphasizing the multi-system nature of the condition.

Citation

Patel MA, Fraser DD, Daley M, et al. The plasma proteome differentiates the multisystem inflammatory syndrome in children (MIS-C) from children with SARS-CoV-2 negative sepsis. (2024) Molecular Medicine, DOI: 10.1186/s10020-024-00806-x

Protein biomarkers predict drug response in pediatric IBD

A team from the Erasmus MC-Sophia Children’s Hospital in Rotterdam used plasma proteomics to identify predictive drug response biomarkers in children with Inflammatory Bowel Disease (IBD). In this study, the Olink® Target 96 Inflammation panel was able to identify differences in baseline proteomics between IBD patients who did or did not continue to respond to anti-TNFα monoclonal antibody therapy with Infliximab (IFX).

Levels of seven inflammatory proteins were significantly higher in patients who eventually discontinued IFX therapy due to loss of response compared to those showing long-term positive clinical benefit. This suggested that patients with subsequent loss of response to IFX treatment have increased immune activation before start of therapy. Supporting this, the seven proteins identified also showed associations with several clinical measures of disease activity.

Citation

Winter DA, de Bruyne P, van der Woude J, et al. Biomarkers predicting the effect of anti-TNF treatment in paediatric and adult inflammatory bowel disease. (2024) Journal of Pediatric Gastroenterology and Nutrition, DOI: 10.1002/jpn3.12221

Gal-9 mediates chemotherapy-induced intestinal damage

In this fascinating in vitro study, 3D intestinal organoids were used to model the proteomic response to chemotherapy-induced damage of the intestinal epithelium. This can be a significant problem in treating cancer patients and is believed to involve immune activation with T cell involvement. A group from the University Medical Center in Utrecht exposed co-cultures of intestinal organoids and T cells to multiple chemotherapy drugs and measured secreted proteins in the conditioned culture medium using the Olink® Target 96 Immuno-Oncology panel.

Several cytokines and chemokines were secreted from organoids exposed to chemotherapy agents, with the immune regulator galectin-9 (Gal-9) showing the most significant response. The significance of this finding was strengthened in follow-up experiments where anti-Gal-9 antibodies or CRISPR/Cas9-mediated Gal-9 knock-out blocked the activation of T cells by chemotherapy-exposed organoids in co-cultures.

Citation

Jansen SA, Cutilli A, de Koning C, et al. Chemotherapy-induced intestinal epithelial damage directly promotes galectin-9-driven modulation of T cell behavior. (2024) iScience, DOI: 10.1016/j.isci.2024.110072

Poor oral health problems increase dementia risk via specific plasma proteins

A study by scientists from multiple centers looked at the links between poor oral health problems (POHP) and the risk of dementia. Analyzing the UK Biobank Pharma Proteomics Project (UKB-PPP) dataset, 1,463 proteins were measured in over 37,000 participants aged between 50-74 years old using Olink ® Explore 1536. These were divided into subjects with and without POHP, who were followed for up to 15 years for development of incident dementia.

POHP increased the risk of all-cause dementia by 17%, with a greater degree of statistical significance in women compared to men. A total of 18 proteins showed statistically significant association with POHP with an effect size greater than the pre-set threshold. Mediation analysis showed that GDF15 explained 28% of the total effect of POHP on incident dementia. Principal component analysis indicated that the top 4 proteins (GDF15, IL19, MMP12, and ACVRL1) explained 11% of the POHP-dementia effect measured as a pure indirect effect. Pathway analysis of the GDF15 cluster of proteins using the Olink Insight online bioinformatics resource indicated transmembrane receptor protein tyrosine kinase signaling as the dominant pathway.

Citation

Beydoun MA, Beydoun HA, Hu YH, et al. Plasma proteomic biomarkers and the association between poor cardiovascular health and incident dementia: The UK Biobank study. (2024) Brain, Behavior, and Immunity, DOI: 10.1016/j.bbi.2024.05.005