An AI-guided signature reveals the nature of the shared proximal pathways of host immune response in MIS-C and Kawasaki disease
Sahoo, D.; Dattatray, G.; Shimizu, C.; Kim, J.; Khandelwal, S.; Tremoulet, A. H.; Kanegaye, J.; Pediatric Emergency Medicine Kawasaki Disease Research Group, ; Bocchini, J.; Das, S.; Burns, J. C.; Ghosh, P.
Show abstract
A significant surge in cases of multisystem inflammatory syndrome in children (MIS-C, also called Pediatric Inflammatory Multisystem Syndrome - PIMS) has been observed amidst the COVID-19 pandemic. MIS-C shares many clinical features with Kawasaki disease (KD), although clinical course and outcomes are divergent. We analyzed whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues from these patients using a computational toolbox of two gene signatures, i.e., the 166-gene viral pandemic (ViP) signature, and its 20-gene severe (s)ViP subset that were developed in the context of SARS-CoV-2 infection and a 13-transcript signature previously demonstrated to be diagnostic for KD. Our analyses revealed that KD and MIS-C are on the same continuum of the host immune response as COVID-19. While both the pediatric syndromes converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures also revealed unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Aberrant peripheral immune responses in acute Kawasaki disease with single-cell sequencing 95%
- Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity 95%
- COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and may be modified by dexamethasone 95%
Similar papers in this journal
- Longitudinal characterization of circulating neutrophils uncovers distinct phenotypes associated with disease severity in hospitalized COVID-19 patients 95%
- Deep immune profiling reveals early-stage and highly coordinated immune responses in mild COVID-19 patients 95%
- Rewired type I IFN signaling is linked to age-dependent differences in COVID-19 94%
Similar papers in this journal
- JAK inhibition decreases the autoimmune burden in Down syndrome 94%
- Prolonged T-cell activation and long COVID symptoms independently associate with severe disease at 3 months in a UK cohort of hospitalized COVID-19 patients 94%
- Intra-ocular dendritic cells are increased in HLA-B27 associated acute anterior uveitis 93%
Similar papers in this journal
- Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity 95%
- Early immune pathology and persistent dysregulation characterise severe COVID-19 95%
- Functional proteomic profiling links deficient DNA clearance to mortality in patients with severe COVID-19 pneumonia 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.