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Transcript abundance patterns in Kawasaki disease patients with intravenous immunoglobulin resistance.

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.

SUBMITTER: Fury W

PROVIDER: S-EPMC2929310 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Transcript abundance patterns in Kawasaki disease patients with intravenous immunoglobulin resistance.

Fury Wen W Tremoulet Adriana H AH Watson Virginia E VE Best Brookie M BM Shimizu Chisato C Hamilton Jennifer J Kanegaye John T JT Wei Yi Y Kao Chiayi C Mellis Scott S Lin Calvin C Burns Jane C JC

Human immunology 20100620 9

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 t ...[more]

PMID: 20600450

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Project description:BackgroundAbout 10-20% of Kawasaki disease (KD) patients are resistant to the initial infusion of intravenous immunoglobin (IVIG). The aim of this study was to assess whether IVIG resistance in KD patients could be predicted using standard clinical and laboratory features.MethodsData were from two cohorts: a Korean cohort of 7101 KD patients from 2015 to 2017 and a cohort of 649 KD patients from San Diego enrolled from 1998 to 2021. Features included laboratory values, the worst Z-score from the initial echocardiogram or during hospitalization, and the five clinical KD signs at presentation.ResultsFive machine learning models achieved a maximum median AUC of 0.711 [IQR: 0.706-0.72] in the Korean cohort and 0.696 [IQR: 0.609-0.722] in the San Diego cohort during stratified 10-fold cross-validation using significant laboratory features identified from univariate analysis. Adding the Z-score, KD clinical signs, or both did not considerably improve the median AUC in either cohort.ConclusionsUsing commonly measured clinical laboratory data alone or in conjunction with echocardiographic findings and clinical features is not sufficient to predict IVIG resistance. Further attempts to predict IVIG resistance will need to incorporate additional data such as transcriptomics, proteomics, and genetics to achieve meaningful predictive utility.ImpactWe demonstrated that laboratory, echocardiographic, and clinical findings cannot predict intravenous immunoglobin (IVIG) resistance to a clinically meaningful extent using machine learning in a homogenous Asian or ethnically diverse population of patients with Kawasaki disease (KD). Visualizing these features using uniform manifold approximation and projection (UMAP) is an important step to evaluate predictive utility in a qualitative manner. Further attempts to predict IVIG resistance in KD patients will need to incorporate novel biomarkers or other specialized features such as genetic differences or transcriptomics to be clinically useful.

Project description:BackgroundIntravenous immunoglobulin (IVIG) has been the mainstay of treatment for Kawasaki disease (KD) over the past decades. However, 10-20% of KD patients are resistant to IVIG treatment which puts those patients at high risk of coronary artery lesions (CALs). Therefore, it is important to predict whether patients will be resistant to IVIG before the treatment. This study aimed to investigate the risk factors for IVIG non-responsive patients with KD.MethodsThis study enrolled patients diagnosed with KD and divided them into two groups, IVIG responders and IVIG non-responders. We compared the differences in demographics and clinical data between the two groups. Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance were determined by multiple logistic regression analysis and receiver operating characteristic (ROC) curve analysis.ResultsIn total, 907 KD patients were reviewed, with 841 IVIG responders and 66 IVIG non-responders. Patients in IVIG responders were younger than IVIG non-responders. The length of hospitalization of the IVIG non-responders was significantly longer than IVIG responders. The neutrophils%, C-reaction protein (CRP), and CRP/albumin ratio in IVIG responders were significantly lower than in IVIG non-responders (P < 0.05). The lymphocyte% and Albumin in IVIG responders were significantly higher than in IVIG non-responders. Multivariable logistic regression analysis demonstrated that albumin (OR = 0.881, 95% CI, 0.781 to 0.994, p-value = 0.039) was an independent risk factor for predicting IVIG resistance. The area under the ROC curve was 0.644, with a cut-off of ≤ 33.4 g/L determined by Youden's index. The sensitivity and specificity in predicting IVIG resistance were 40.91% and 83.47%, respectively.ConclusionAlbumin can serve as a potential predicting marker for IVIG resistance in KD. A lower albumin level may be useful for identifying KD patients with a high risk of IVIG resistance to guide further therapy strategies.

Dataset Information

Transcript abundance patterns in Kawasaki disease patients with intravenous immunoglobulin resistance.

Publications

Transcript abundance patterns in Kawasaki disease patients with intravenous immunoglobulin resistance.

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