Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock

Hector R. Wong*, Natalie Z. Cvijanovich, Geoffrey L. Allen, Neal J. Thomas, Robert J. Freishtat, Nick Anas, Keith Meyer, Paul A. Checchia, Scott L. Weiss, Thomas P. Shanley, Michael T. Bigham, Sharon Banschbach, Eileen Beckman, Kelli Harmon, Jerry J. Zimmerman

*Corresponding author for this work

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Rationale: Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects. Objectives: To determine the effect of adjunctive corticosteroids on the genomic response of pediatric septic shock. Methods: We retrospectively analyzed an existing transcriptomic database of pediatric septic shock. Subjects receiving any formulation of systemic corticosteroids at the time of blood draw for microarray analysis were classified in the septic shock corticosteroid group. We compared normal control subjects (n = 52), a septic shock no corticosteroid group (n = 110), and a septic shock corticosteroid group (n = 70) using analysis of variance. Genes differentially regulated between the no corticosteroid group and the corticosteroid group were analyzed using Ingenuity Pathway Analysis. Measurements and Main Results: The two study groups did not differ with respect to illness severity, organ failure burden, mortality, or mortality risk. There were 319 gene probes differentially regulated between the no corticosteroid group and the corticosteroid group. These genes corresponded predominately to adaptive immunity-related signaling pathways, and were down-regulated relative to control subjects.Notably, the degree of down-regulationwas significantly greater in the corticosteroid group, compared with the no corticosteroid group. A similar pattern was observed for genes corresponding to the glucocorticoid receptor signaling pathway. Conclusions: Administrationof corticosteroids inpediatric septic shock is associated with additional repression of genes corresponding to adaptive immunity. These data should be taken into account when considering the benefit to risk ratio of adjunctive corticosteroids for septic shock.

Original languageEnglish (US)
Pages (from-to)940-946
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume189
Issue number8
DOIs
StatePublished - Apr 15 2014

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Adaptive Immunity
Septic Shock
Adrenal Cortex Hormones
Pediatrics
Genes
Mortality
Glucocorticoid Receptors
Microarray Analysis
Analysis of Variance

Keywords

  • Adaptive immunity
  • Corticosteroids
  • Gene expression
  • Microarray
  • Sepsis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Wong, H. R., Cvijanovich, N. Z., Allen, G. L., Thomas, N. J., Freishtat, R. J., Anas, N., ... Zimmerman, J. J. (2014). Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock. American journal of respiratory and critical care medicine, 189(8), 940-946. https://doi.org/10.1164/rccm.201401-0171OC
Wong, Hector R. ; Cvijanovich, Natalie Z. ; Allen, Geoffrey L. ; Thomas, Neal J. ; Freishtat, Robert J. ; Anas, Nick ; Meyer, Keith ; Checchia, Paul A. ; Weiss, Scott L. ; Shanley, Thomas P. ; Bigham, Michael T. ; Banschbach, Sharon ; Beckman, Eileen ; Harmon, Kelli ; Zimmerman, Jerry J. / Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock. In: American journal of respiratory and critical care medicine. 2014 ; Vol. 189, No. 8. pp. 940-946.
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abstract = "Rationale: Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects. Objectives: To determine the effect of adjunctive corticosteroids on the genomic response of pediatric septic shock. Methods: We retrospectively analyzed an existing transcriptomic database of pediatric septic shock. Subjects receiving any formulation of systemic corticosteroids at the time of blood draw for microarray analysis were classified in the septic shock corticosteroid group. We compared normal control subjects (n = 52), a septic shock no corticosteroid group (n = 110), and a septic shock corticosteroid group (n = 70) using analysis of variance. Genes differentially regulated between the no corticosteroid group and the corticosteroid group were analyzed using Ingenuity Pathway Analysis. Measurements and Main Results: The two study groups did not differ with respect to illness severity, organ failure burden, mortality, or mortality risk. There were 319 gene probes differentially regulated between the no corticosteroid group and the corticosteroid group. These genes corresponded predominately to adaptive immunity-related signaling pathways, and were down-regulated relative to control subjects.Notably, the degree of down-regulationwas significantly greater in the corticosteroid group, compared with the no corticosteroid group. A similar pattern was observed for genes corresponding to the glucocorticoid receptor signaling pathway. Conclusions: Administrationof corticosteroids inpediatric septic shock is associated with additional repression of genes corresponding to adaptive immunity. These data should be taken into account when considering the benefit to risk ratio of adjunctive corticosteroids for septic shock.",
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author = "Wong, {Hector R.} and Cvijanovich, {Natalie Z.} and Allen, {Geoffrey L.} and Thomas, {Neal J.} and Freishtat, {Robert J.} and Nick Anas and Keith Meyer and Checchia, {Paul A.} and Weiss, {Scott L.} and Shanley, {Thomas P.} and Bigham, {Michael T.} and Sharon Banschbach and Eileen Beckman and Kelli Harmon and Zimmerman, {Jerry J.}",
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Wong, HR, Cvijanovich, NZ, Allen, GL, Thomas, NJ, Freishtat, RJ, Anas, N, Meyer, K, Checchia, PA, Weiss, SL, Shanley, TP, Bigham, MT, Banschbach, S, Beckman, E, Harmon, K & Zimmerman, JJ 2014, 'Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock', American journal of respiratory and critical care medicine, vol. 189, no. 8, pp. 940-946. https://doi.org/10.1164/rccm.201401-0171OC

Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock. / Wong, Hector R.; Cvijanovich, Natalie Z.; Allen, Geoffrey L.; Thomas, Neal J.; Freishtat, Robert J.; Anas, Nick; Meyer, Keith; Checchia, Paul A.; Weiss, Scott L.; Shanley, Thomas P.; Bigham, Michael T.; Banschbach, Sharon; Beckman, Eileen; Harmon, Kelli; Zimmerman, Jerry J.

In: American journal of respiratory and critical care medicine, Vol. 189, No. 8, 15.04.2014, p. 940-946.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock

AU - Wong, Hector R.

AU - Cvijanovich, Natalie Z.

AU - Allen, Geoffrey L.

AU - Thomas, Neal J.

AU - Freishtat, Robert J.

AU - Anas, Nick

AU - Meyer, Keith

AU - Checchia, Paul A.

AU - Weiss, Scott L.

AU - Shanley, Thomas P.

AU - Bigham, Michael T.

AU - Banschbach, Sharon

AU - Beckman, Eileen

AU - Harmon, Kelli

AU - Zimmerman, Jerry J.

PY - 2014/4/15

Y1 - 2014/4/15

N2 - Rationale: Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects. Objectives: To determine the effect of adjunctive corticosteroids on the genomic response of pediatric septic shock. Methods: We retrospectively analyzed an existing transcriptomic database of pediatric septic shock. Subjects receiving any formulation of systemic corticosteroids at the time of blood draw for microarray analysis were classified in the septic shock corticosteroid group. We compared normal control subjects (n = 52), a septic shock no corticosteroid group (n = 110), and a septic shock corticosteroid group (n = 70) using analysis of variance. Genes differentially regulated between the no corticosteroid group and the corticosteroid group were analyzed using Ingenuity Pathway Analysis. Measurements and Main Results: The two study groups did not differ with respect to illness severity, organ failure burden, mortality, or mortality risk. There were 319 gene probes differentially regulated between the no corticosteroid group and the corticosteroid group. These genes corresponded predominately to adaptive immunity-related signaling pathways, and were down-regulated relative to control subjects.Notably, the degree of down-regulationwas significantly greater in the corticosteroid group, compared with the no corticosteroid group. A similar pattern was observed for genes corresponding to the glucocorticoid receptor signaling pathway. Conclusions: Administrationof corticosteroids inpediatric septic shock is associated with additional repression of genes corresponding to adaptive immunity. These data should be taken into account when considering the benefit to risk ratio of adjunctive corticosteroids for septic shock.

AB - Rationale: Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects. Objectives: To determine the effect of adjunctive corticosteroids on the genomic response of pediatric septic shock. Methods: We retrospectively analyzed an existing transcriptomic database of pediatric septic shock. Subjects receiving any formulation of systemic corticosteroids at the time of blood draw for microarray analysis were classified in the septic shock corticosteroid group. We compared normal control subjects (n = 52), a septic shock no corticosteroid group (n = 110), and a septic shock corticosteroid group (n = 70) using analysis of variance. Genes differentially regulated between the no corticosteroid group and the corticosteroid group were analyzed using Ingenuity Pathway Analysis. Measurements and Main Results: The two study groups did not differ with respect to illness severity, organ failure burden, mortality, or mortality risk. There were 319 gene probes differentially regulated between the no corticosteroid group and the corticosteroid group. These genes corresponded predominately to adaptive immunity-related signaling pathways, and were down-regulated relative to control subjects.Notably, the degree of down-regulationwas significantly greater in the corticosteroid group, compared with the no corticosteroid group. A similar pattern was observed for genes corresponding to the glucocorticoid receptor signaling pathway. Conclusions: Administrationof corticosteroids inpediatric septic shock is associated with additional repression of genes corresponding to adaptive immunity. These data should be taken into account when considering the benefit to risk ratio of adjunctive corticosteroids for septic shock.

KW - Adaptive immunity

KW - Corticosteroids

KW - Gene expression

KW - Microarray

KW - Sepsis

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