Multiomic Analysis of Neuroinflammation and Occult Infection in Sudden Infant Death Syndrome Article Swipe
Prashanth Ramachandran
,
Benjamin W. Okaty
,
Molly Riehs
,
Anne E. Wapniarski
,
Daniel Hershey
,
Hani Harb
,
Maham Zia
,
Elisabeth A. Haas
,
Sanda Alexandrescu
,
Lynn A. Sleeper
,
Sara O. Vargas
,
Mark Gorman
,
Steven C. Campman
,
Othon J. Mena
,
Keith Levert
,
Keith Hyland
,
Richard D. Goldstein
,
Michael R. Wilson
,
Robin L. Haynes
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1001/jamaneurol.2023.5387
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1001/jamaneurol.2023.5387
Importance Antemortem infection is a risk factor for sudden infant death syndrome (SIDS)—the leading postneonatal cause of infant mortality in the developed world. Manifestations of infection and inflammation are not always apparent in clinical settings or by standard autopsy; thus, enhanced resolution approaches are needed. Objective To ascertain whether a subset of SIDS cases is associated with neuroinflammation and occult infection. Design, Setting, and Participants In this case-control study, postmortem fluids from SIDS cases and controls collected between July 2011 and November 2018 were screened for elevated inflammatory markers, specifically cerebrospinal fluid (CSF) neopterin and CSF and serum cytokines. CSF, liver, and brain tissue from SIDS cases with elevated CSF neopterin were subjected to metagenomic next-generation sequencing (mNGS) to probe for infectious pathogens. Brainstem tissue from a subset of these cases was analyzed by single-nucleus RNA sequencing (snRNAseq) to measure cell type–specific gene expression associated with neuroinflammation and infection. All tissue and fluid analyses were performed from April 2019 to January 2023 in a pathology research laboratory. Included was autopsy material from infants dying of SIDS and age-matched controls dying of known causes. Exposures There were no interventions or exposures. Main Outcomes and Measures CSF neopterin levels were measured by high-performance liquid chromatography. Cytokines were measured by multiplex fluorometric assay. mNGS was performed on liver, CSF, brain, and brainstem tissue. snRNAseq was performed on brainstem tissue. Results A cohort of 71 SIDS cases (mean [SD] age, 55.2 [11.4] postconceptional weeks; 42 male [59.2%]) and 20 controls (mean [SD] age, 63.2 [16.9] postconceptional weeks; 11 male [55.0%]) had CSF and/or serum available. CSF neopterin was screened in 64 SIDS cases and 15 controls, with no exclusions. Tissues from 6 SIDS cases were further analyzed. For CSF neopterin measures, SIDS samples were from infants with mean (SD) age of 54.5 (11.3) postconceptional weeks (38 male [59.4%]) and control samples were from infants with mean (SD) age of 61.5 (17.4) postconceptional weeks (7 male [46.7%]). A total of 6 SIDS cases (9.3%) with high CSF neopterin were identified, suggestive of neuroinflammation. mNGS detected human parechovirus 3 (HPeV3) in tissue and CSF from 1 of these 6 cases. snRNAseq of HPeV3-positive brainstem tissue (medulla) revealed dramatic enrichment of transcripts for genes with predominately inflammatory functions compared with 3 age-matched SIDS cases with normal CSF neopterin levels. Conclusions and Relevance Next-generation molecular tools in autopsy tissue provide novel insight into pathogens that go unrecognized by normal autopsy methodology, including in infants dying suddenly and unexpectedly.
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Metadata
- Type
- letter
- Language
- en
- Landing Page
- https://doi.org/10.1001/jamaneurol.2023.5387
- OA Status
- green
- Cited By
- 14
- References
- 27
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391324472
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4391324472Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1001/jamaneurol.2023.5387Digital Object Identifier
- Title
-
Multiomic Analysis of Neuroinflammation and Occult Infection in Sudden Infant Death SyndromeWork title
- Type
-
letterOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-01-29Full publication date if available
- Authors
-
Prashanth Ramachandran, Benjamin W. Okaty, Molly Riehs, Anne E. Wapniarski, Daniel Hershey, Hani Harb, Maham Zia, Elisabeth A. Haas, Sanda Alexandrescu, Lynn A. Sleeper, Sara O. Vargas, Mark Gorman, Steven C. Campman, Othon J. Mena, Keith Levert, Keith Hyland, Richard D. Goldstein, Michael R. Wilson, Robin L. HaynesList of authors in order
- Landing page
-
https://doi.org/10.1001/jamaneurol.2023.5387Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/10825787Direct OA link when available
- Concepts
-
Neopterin, Medicine, Sudden infant death syndrome, Autopsy, Pathology, Cerebrospinal fluid, Neuroinflammation, Biomarker, Inflammation, Immunology, Pediatrics, Biology, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
14Total citation count in OpenAlex
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2025: 4, 2024: 10Per-year citation counts (last 5 years)
- References (count)
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27Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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