Serum cytokine panels in pediatric clinical practice.

Background: Cytokines are soluble signaling proteins that regulate inflammation and coordinate immune responses. Serum cytokine panels are increasingly used in medical practice, yet our understanding of cytokines as biomarkers for disease remains limited.
Objective: We sought to analyze real-world single-center use of a multiplexed cytokine panel, correlate its results with diagnosis and severity, and explore its use in pediatric practice.
Methods: A multiplexed cytokine panel, able to return same-day results, was implemented in April 2020 at the Children's Hospital of Philadelphia (Philadelphia, Pa) and its performance was validated for clinical use. Coded patient data were collected using the REDCap database, and correlations between cytokine levels and outcomes of interest were analyzed retrospectively.
Results: Cytokine levels correlate with acuity of care, with patients admitted to the pediatric intensive care unit having the highest cytokine values. Patients with familial hemophagocytic lymphohistiocytosis (fHLH) showed prominent peaks in IFN-γ, IL-10, and TNF, whereas patients with sepsis exhibited high IL-6 and IL-8 with relatively modest IFN-γ. Cytokine release syndrome (CRS) after chimeric antigen receptor T-cell therapy often demonstrated pan-panel positivity at peak levels, with a similar pattern as that of fHLH. A ratio of [IFN-γ] + [IL-10]/[IL-6] + [IL-8] levels was able to distinguish fHLH and CRS from severe sepsis.
Conclusions: Cytokine levels correlate with severity of illness and can help differentiate between syndromes that present similarly, including fHLH and CRS compared with sepsis. Cytokine panels can be used as biomarkers to inform diagnosis and management decisions, but significant work remains to dissect complex clinical patterns of disease.
Competing Interests: Disclosure statement This study was supported by the National Institutes of Health T32 Pediatric Hematology Research Training Program (grant no. 5T32HL007150-47 to P.M.G.). It was also supported by grants from the National Institutes of Health (grant no. K23 DK119585 to M.A.C. and grant no. R01DK127044 to J.R.K.). Disclosure of potential conflict of interest: D. T. Teachey serves on advisory boards for Sobi, Jazz, and BEAM Therapeutics; receives research funding from NeoImmune Tech and BEAM Therapeutics; and has multiple patents or patents pending on CART, including a patent on cytokine profiling after treatment with CART (US 11747346, biomarkers predictive of CRS). S. W. Canna has provided consulting for Sobi, Apollo, and Bristol-Myers Squibb; and received speaking fees from Sobi and PracticePointCME. M. P. Lambert is an advisory board member for Octapharma, Dova, Principia, Rigel, Argenx, PDSA, 22qSociety and CdLS Foundation; a consultant for Novartis Dova, Principia, Argenx, Rigel, Sobi, Sanofi and Janssen, and has received research funding from FWGBD, PDSA, NIH, Sysmex, Novartis, Principia, Argenx, Dova, Octapharma and Sanofi. The rest of the authors declare that they have no relevant conflicts of interest.
(Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)