Novel X-Linked Inhibitor of Apoptosis Mutation in Very Early-Onset Inflammatory Bowel Disease Child Successfully Treated with HLA-Haploidentical Hemapoietic Stem Cells Transplant after Removal of αβT and B Cells

Cristina Cifaldi, Maria Chiriaco, Gigliola Di Matteo, Silvia Di Cesare, Scarselli Alessia, Paola De Angelis, Francesca Rea, Giulia Angelino, Maria Pastore, Valentina Ferradini, Daria Pagliara, Caterina Cancrini, Paolo Rossi, Alice Bertaina, Andrea Finocchi

Research output: Contribution to journalArticle


Monogenic defects in genes related to primary immunodeficiencies can be responsible for inflammatory bowel disease (IBD). Mutations in the X-linked inhibitor of apoptosis (XIAP) gene have been described in several patients suffering from IBD and, in particular, with very early-onset inflammatory bowel disease (VEOIBD) features. We report a VEOIBD child with a novelXIAPgene mutation characterized by a complicated disease course, which is unresponsive to several medical treatment options. A next-generation sequencing was performed and revealed ade novohemizygous mutation inXIAPgene: c.565T>C p.L189P. After mutation discovery, we investigated the XIAP protein expression and nucleotide-binding oligomerization domain protein 2 (NOD2) signaling by western blotting. Flow-cytometry was used to analyze intracellular protein expression in different cell subsets and T cell apoptosis. We observed reduced protein expression in lymphocytes, granulocytes, monocytes, an Epstein-Barr virus-immortalized B cell line as well as increased apoptosis, and impairment in NOD2 signaling. The child was successfully treated with HLA-haploidentical hemapoietic stem cells transplant, acquired from his mother, afterex vivoelimination of α/β T cells and CD19 B cells. One year after the transplant, we repeated the analysis to appreciate the changes in his impairments. The recovery of XIAP protein expression, function, and normalization of apoptosis were observed. Our report emphasizes the important role of genetic analysis in the diagnosis of VEOIBD, illustrates the complete immunological and gastrointestinal recovery after transplant, and shows one of the few successful transplant cases of XIAP patients.

Original languageEnglish
Pages (from-to)1893
JournalFrontiers in Immunology
Publication statusPublished - 2017


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