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. 2010 Sep;71(9):865-73.
doi: 10.1016/j.humimm.2010.06.008. Epub 2010 Jun 20.

Transcript abundance patterns in Kawasaki disease patients with intravenous immunoglobulin resistance

Wen Fury  1 , Adriana H Tremoulet, Virginia E Watson, Brookie M Best, Chisato Shimizu, Jennifer Hamilton, John T Kanegaye, Yi Wei, Chiayi Kao, Scott Mellis, Calvin Lin, Jane C Burns
Affiliations

Transcript abundance patterns in Kawasaki disease patients with intravenous immunoglobulin resistance

Wen Fury et al. Hum Immunol. 2010 Sep.

Abstract

Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients comprise at least 20% of treated patients and are at high risk for coronary artery abnormalities. If identified early in the course of the disease, such patients may benefit from additional anti-inflammatory therapy. The aim of this study was to compare the transcript abundance between IVIG resistant and -responsive KD patients, to identify biomarkers that might differentiate between these two groups and to generate new targets for therapies in IVIG resistant KD patients. We compared the transcript abundance profiles of whole-blood RNA on Agilent arrays from acute and convalescent KD subjects and age-similar, healthy controls. KD subjects were stratified as IVIG resistant or -responsive based on response to initial IVIG therapy. Transcript abundance was higher for IL-1 pathway genes (IL-1 receptor, interleukin receptor associated kinase, p38 mitogen-activated protein kinase), and MMP-8. These findings point to candidate biomarkers that may predict IVIG resistance in acute KD patients. The results also underscore the importance of the IL-1 pathway as a mediator of inflammation in KD and suggest that IL-1 or its receptor may be reasonable targets for therapy, particularly for IVIG resistant patients.

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Figures

Figure 1
Figure 1
Flow diagram of the groups compared for transcript abundance
Figure 2
Figure 2. Venn diagram of disease-specific transcripts differentially abundant in acute KD subjects (n=20) compared to healthy controls (n=9) and convalescent KD subjects (n=20)
A. Overlap of probes that were less abundant in acute KD subjects and more abundant in both healthy controls and convalescent KD subjects. B. Overlap of probes that were more abundant in acute KD subjects and less abundant in both healthy controls and convalescent KD subjects.
Figure 3
Figure 3. Ingenuity Network Pathway Analysis of MMP-8, S100 proteins (S100A8, S100A9 and S100A12), and carcinoembryonic antigen-related cell adhesion molecules (CEACAM 1 and CEACAM 8)
A grey shaded molecule refers to a probe that was more abundant in acute KD subjects vs. both convalescent KD subjects and healthy control.
Figure 4
Figure 4. Ingenuity Canonical Pathway Analysis of the genes associated with the top 200 probes that are differentially abundant between acute KD subjects and both convalescent KD subjects and healthy control
A grey shaded molecule refers to a probe that was more abundant in acute KD subjects vs. both convalescent KD subjects and healthy control.
Figure 4
Figure 4. Ingenuity Canonical Pathway Analysis of the genes associated with the top 200 probes that are differentially abundant between acute KD subjects and both convalescent KD subjects and healthy control
A grey shaded molecule refers to a probe that was more abundant in acute KD subjects vs. both convalescent KD subjects and healthy control.
Figure 4
Figure 4. Ingenuity Canonical Pathway Analysis of the genes associated with the top 200 probes that are differentially abundant between acute KD subjects and both convalescent KD subjects and healthy control
A grey shaded molecule refers to a probe that was more abundant in acute KD subjects vs. both convalescent KD subjects and healthy control.
Figure 5
Figure 5. Venn diagram of overlap between disease-specific transcripts differentially abundant in acute KD (n=20) and IVIG-resistant KD subjects (n=8)
Overlap of probes that were more abundant in acute KD and IVIG-resistant KD subjects than in IVIG-responsive KD subjects.
Figure 6
Figure 6. Ingenuity Canonical Pathway Analysis of the genes associated with the 356 probes that were increased in both acute KD and IVIG-resistant KD subjects
A grey shaded molecule refers to a probe that was more abundant in acute KD subjects vs. both convalescent KD subjects and healthy control as well as more abundant in IVIG-resistant compared to IVIG-responsive KD subjects.
Figure 7
Figure 7. Comparison of MMP-8 relative transcript abundance levels by RT PCR in IVIG-resistant and IVIG-responsive KD subjects
Box plots demonstrate the median, 25th and 75th percentiles. Whiskers identify the 5th and 95th percentiles.
Figure 8
Figure 8. Comparison of MMP-8 serum levels in an independent cohort of acute and convalescent KD subjects
Box plots demonstrate the median, 25th and 75th percentiles. Whiskers identify the 5th and 95th percentiles.
See this image and copyright information in PMC

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