Predictors of Intravenous Immunoglobulin Nonresponse and Racial Disparities in Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in American children. Intravenous immunoglobulin (IVIG) nonresponse is a known risk factor for cardiac sequelae. Previously reported risk factors for nonresponse include age, male sex and laboratory abnormalities. We set out to identify additional risk factors for IVIG nonresponse in a racially diverse KD population. METHODS: We conducted a retrospective chart review at a referral center in the Southeastern United States of children meeting ICD-9 (International Statistical Classification of Disease and Related Health Problems) criteria for KD and being treated with IVIG. RESULTS: Four-hundred and fifty-nine children met inclusion criteria, 67 were excluded for subsequent rheumatologic diagnosis, unknown race, or failure to meet the American Heart Association guideline criteria. Our final cohort consisted of 392 subjects, with median age of 2.7 years, 65.1% male, 66.1% White, 24.2% Black, 4.9% Asian and 82.9% responded to a single dose of IVIG. Coronary ectasia or aneurysm developed in 27%; 7.4% developed aneurysms and 2.3% giant coronary aneurysms. Nonresponders were more likely to be Black, have higher white blood cell, erythrocyte sedimentation rate and C-reactive protein, lower hemoglobin, develop ectasia or aneurysm and require critical care and hospital readmission. Responders achieved echocardiographic normalization more often compared with nonresponders (81.3% vs. 60.9%, P = 0.002) and coronary artery pseudonormalization (87.2% vs. 69.7%, P = 0.03) at 1 year. Black nonresponders had the slowest normalization at 1 year (52.9%, P = 0.02). CONCLUSIONS: Nonresponders have higher rates and greater severity of coronary involvement than responders. Our study uniquely demonstrates Black race as a risk factor for nonresponse and for delayed normalization of cardiac involvement at 1-year follow-up.

A database of reaction monitoring mass spectrometry assays for elucidating therapeutic response in cancer.

PURPOSE: The Quantitative Assay Database (QuAD), http://proteome.moffitt.org/QUAD/, facilitates widespread implementation of quantitative mass spectrometry in cancer biology and clinical research through sharing of methods and reagents for monitoring protein expression and modification. EXPERIMENTAL DESIGN: Liquid chromatography coupled to multiple reaction monitoring (LC-MRM) mass spectrometry assays are developed using SDS-PAGE fractionated lysates from cancer cell lines. Pathway maps created using GeneGO Metacore provide the biological relationships between proteins and illustrate concepts for multiplexed analysis; each protein can be selected to examine assay development at the protein and peptide levels. RESULTS: The coupling of SDS-PAGE and multiple reaction monitoring mass spectrometry screening has been used to detect 876 peptides from 218 cancer-related proteins in model systems including colon, lung, melanoma, leukemias, and myeloma, which has led to the development of 95 quantitative assays including stable-isotope-labeled peptide standards. Methods are published online and peptide standards are made available to the research community. Protein expression measurements for heat shock proteins, including a comparison with ELISA and monitoring response to the HSP90 inhibitor, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), are used to illustrate the components of the QuAD and its potential utility. CONCLUSIONS AND CLINICAL RELEVANCE: This resource enables quantitative assessment of protein components of signaling pathways and biological processes and holds promise for systematic investigation of treatment responses in cancer.