One explanation in the AIN case with KD is that the neutrophil count sampled in peripheral blood does not always reflect the neutrophil count in the marginated pool or in the tissues

One explanation in the AIN case with KD is that the neutrophil count sampled in peripheral blood does not always reflect the neutrophil count in the marginated pool or in the tissues. for subjects selected for gene expression analysis; Table D in S1 File. Association of 12 genes with IVIG response in subgroup with normal and elevated CRP levels; Table E in S1 File. Association of 12 genes with IVIG response in subgroup with normal and elevated CRP levels.(PPTX) pone.0167434.s004.pptx (72K) Ergoloid Mesylates GUID:?9D69B31E-F1BE-4670-BB5B-AFE9A1034019 Data Availability StatementThis Stanford-led international collaborative effort for Cohort I, II, III, and IV was approved by the Stanford University IRB to perform data science Rabbit Polyclonal to TAS2R38 on these datasets due to nature of the patient electronic medical records of collaborative clinical organizations. Due to these ethical restrictions, these data are available upon request. Requests for the data should be directed to Drs. Burns and Lee as following: Clinical datasets of Cohort I (from November 1989 to August 2014), II (from February 2000 to January 2009), III (from March 2009 to August 2012): Jane C. Burns, MD; ude.dscu@snrubcj, University of California, San Diego (UCSD); Clinical dataset of Cohort IV (from January 2008 to December 2013): JungHwa Lee, MD; moc.iohc@dmjeel. All the gene expression data from Cohort II are available at the GEO public database. The accession number is GSE63881. The normal ranges of GGT and alanine aminotransferase (ALT) are shown in S1A Table and S1B Table respectively, while the normal range of C-reactive protein (CRP) is shown in the footnotes of S1 File. Abstract Background Resistance to intravenous immunoglobulin (IVIG) occurs in 10C20% of patients with Kawasaki disease (KD). The risk of resistance is about two-fold higher in patients with elevated gamma glutamyl transferase (GGT) levels. We sought to understand the biological mechanisms underlying IVIG resistance in patients with elevated GGT levels. Method We explored the association between elevated GGT levels and IVIG-resistance with a cohort of 686 KD patients (Cohort I). Gene expression data from 130 children with acute KD (Cohort II) were analyzed using the R square statistic and false discovery analysis to identify genes that were differentially represented in patients with elevated GGT levels with regard to IVIG responsiveness. Two additional KD cohorts (Cohort III and IV) were used to test the hypothesis that sialylation and GGT may be involved in IVIG resistance through neutrophil apoptosis. Results Thirty-six genes were identified that significantly explained the variations of both GGT levels and IVIG responsiveness in KD patients. After Bonferroni correction, significant associations with IVIG resistance persisted for 12 out of 36 genes among patients with elevated GGT levels and none among patients with normal GGT levels. With the discovery of valuevalue 0.01 using fisher exact test. Global gene expression Ergoloid Mesylates analyses with FDR Of the 130 KD subjects with gene expression data in Cohort II, 100 were IVIG responders and 30 were IVIG nonresponders. At the time of diagnosis, 45 subjects had normal serum GGT levels, and 85 had elevated GGT levels (Table C in S1 File). In multiple hypothesis testing of gene expression for GGT levels and IVIG resistance, the number of true discovered genes decreased with increasing R square values (Fig 3). The median of false discoveries decreased much faster than the total number of discoveries because the event, that a gene can explain the significant variations of the randomized response, can only occur by chance. In analyses of IVIG resistance and elevated GGT levels, the R square thresholds corresponding to a TDR of 99% resulted in discovery of 837 and 613 genes, respectively. Of these, 36 were common to both gene sets (Fig 3 bottom panel). Open in a separate windows Fig Ergoloid Mesylates 3 R2 statistic and FDR analyses with respect to GGT levels and IVIG responsiveness.Top Ergoloid Mesylates left panel: discovery of genes explaining variations in IVIG responsiveness. Top right panel:.