Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency

Hernandez, Nicholas; Melki, Isabelle; Jing, Huie; Habib, Tanwir; Huang, Susie S.Y.; Danielson, Jeffrey; Kula, Tomasz; Drutman, Scott; Belkaya, Serkan; Rattina, Vimel; Lorenzo-Diaz, Lazaro; Boulai, Anais; Rose, Yoann; Kitabayashi, Naoki; Rodero, Mathieu P.; Dumaine, Cecile; Blanche, Stéphane; Lebras, Marie-Noëlle; Leung, Man Chun; Mathew, Lisa Sara; Boisson, Bertrand; Zhang, Shen-Ying; Boisson-Dupuis, Stephanie; Giliani, Silvia; Chaussabel, Damien; Notarangelo, Luigi D.; Elledge, Stephen J.; Ciancanelli, Michael J.; Abel, Laurent; Zhang, Qian; Marr, Nico; Crow, Yanick J.; Su, Helen C.; Casanova, Jean-Laurent

For B-LCL network analysis, a greater than fivefold cut-off was applied to the control groups to generate the target list of IFN-α2b-induced genes. From the 749 up-regulated genes in the healthy controls, 84 were induced at > fivefold. This gene was then used to filter the IRF9-deficient patient, using the same >1.5fold cut-off applied in RNA-seq analysis. In the IRF9-deficient patient, a total of 37 genes were found to be induced at >1.5-fold, and 47 were nonresponsive. These two lists were then entered into Interferome v2.01 and queried for ISGs, using similar experimental criteria as the current study (Rusinova et al., 2013) . Of the 37 genes found to be responsive in the IRF9-deficient patient, 24 were identified as ISGs. Of the 47 nonresponsive genes, 39 were identified as ISGs. The combined ISG gene lists for the IRF9-deficient patient was used to conduct network analysis in Gene-MAN IA, using biological process based Gene Ontology weighting method and the maximum resultant genes set to 20 (Warde-Farley et al., 2010) . The network was examined using both biological pathway (4.35%) and physical interactions (67.64%).