Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease

Preeti Jaggi, Asuncion Mejias, Zhaohui Xu, Han Yin, Melissa Moore-Clingenpeel, Bennett Smith, Jane C. Burns, Adriana H. Tremoulet, Alejandro Jordan-Villegas, Damien J. Chaussabel, Karen Texter, Virginia Pascual, Octavio Ramilo

Research output: Contribution to journalArticle

Abstract

Background Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Methods Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4–6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. Results We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. Conclusion A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG.

Original languageEnglish
Article numbere0197858
JournalPLoS One
Volume13
Issue number5
DOIs
Publication statusPublished - 1 May 2018

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Mucocutaneous Lymph Node Syndrome
Intravenous Immunoglobulins
immunoglobulins
Blood
blood
Genes
Streptococcus
Adenoviridae
fever
Fever
genomics
Passive Immunization
genes
natural killer cells
Biomarkers
disease diagnosis
Platelets
Natural Killer Cells
neutrophils
biomarkers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Jaggi, P., Mejias, A., Xu, Z., Yin, H., Moore-Clingenpeel, M., Smith, B., ... Ramilo, O. (2018). Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease. PLoS One, 13(5), [e0197858]. https://doi.org/10.1371/journal.pone.0197858

Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease. / Jaggi, Preeti; Mejias, Asuncion; Xu, Zhaohui; Yin, Han; Moore-Clingenpeel, Melissa; Smith, Bennett; Burns, Jane C.; Tremoulet, Adriana H.; Jordan-Villegas, Alejandro; Chaussabel, Damien J.; Texter, Karen; Pascual, Virginia; Ramilo, Octavio.

In: PLoS One, Vol. 13, No. 5, e0197858, 01.05.2018.

Research output: Contribution to journalArticle

Jaggi, P, Mejias, A, Xu, Z, Yin, H, Moore-Clingenpeel, M, Smith, B, Burns, JC, Tremoulet, AH, Jordan-Villegas, A, Chaussabel, DJ, Texter, K, Pascual, V & Ramilo, O 2018, 'Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease', PLoS One, vol. 13, no. 5, e0197858. https://doi.org/10.1371/journal.pone.0197858
Jaggi, Preeti ; Mejias, Asuncion ; Xu, Zhaohui ; Yin, Han ; Moore-Clingenpeel, Melissa ; Smith, Bennett ; Burns, Jane C. ; Tremoulet, Adriana H. ; Jordan-Villegas, Alejandro ; Chaussabel, Damien J. ; Texter, Karen ; Pascual, Virginia ; Ramilo, Octavio. / Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease. In: PLoS One. 2018 ; Vol. 13, No. 5.
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abstract = "Background Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Methods Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4–6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. Results We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92{\%} and 100{\%}, respectively) than for GAS (75{\%} and 87{\%}, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. Conclusion A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG.",
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AU - Mejias, Asuncion

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AU - Moore-Clingenpeel, Melissa

AU - Smith, Bennett

AU - Burns, Jane C.

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AU - Jordan-Villegas, Alejandro

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AU - Pascual, Virginia

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N2 - Background Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Methods Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4–6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. Results We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. Conclusion A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG.

AB - Background Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Methods Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4–6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. Results We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. Conclusion A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG.

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