Pediatric-onset Evans syndrome: Heterogeneous presentation and high frequency of monogenic disorders including LRBA and CTLA4 mutations

Caroline Besnard Eva Levy 1 Nathalie Aladjidi Marie-Claude Stolzenberg 2 Aude Magerus-Chatinet Olivier Alibeu 3 Patrick Nitschke 3, 4, 5, 6 Stéphane Blanche 7 Olivier Hermine 8 Eric Jeziorski 9 Judith Landman-Parker Guy Leverger Nizar Mahlaoui 10, 11, 12, 13, 7 Gérard Michel Isabelle Pellier Felipe Suarez 10, 3, 7, 12 Isabelle Thuret 14 Geneviève Saint-Basile Capucine Picard 5, 7 Alain Fischer 11, 3, 15, 5, 6, 12 Bénédicte Neven 11, 3 Frédéric Rieux-Laucat 2 Pierre Quartier 11
Abstract : Evans syndrome (ES) is defined by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. Clinical presentation includes manifestations of immune dysregulation, found in primary immune deficiencies, autoimmune lymphoproliferative syndrome with FAS (ALPS-FAS), Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) and Lipopolysaccharide-Responsive vesicle trafficking Beige-like and Anchor protein (LRBA) defects. We report the clinical history and genetic results of 18 children with ES after excluding ALPS-FAS. Thirteen had organomegaly, five lymphocytic infiltration of non-lymphoid organs, nine hypogammaglobulinemia and fifteen anomalies in lymphocyte phenotyping. Seven patients had genetic defects: three CTLA4 mutations (c.151C\textgreaterT; c.109+1092\₅68-512del; c.110-2A\textgreaterG) identified by Sanger sequencing and four revealed by Next Generation Sequencing: LRBA (c.2450+1C\textgreaterT), STAT3 gain-of-function (c.2147C\textgreaterT; c.2144C\textgreaterT) and KRAS (c.37G\textgreaterT). No feature emerged to distinguish patients with or without genetic diagnosis. Our data on pediatric-onset ES should prompt physicians to perform extensive screening for mutations in the growing pool of genes involved in primary immune deficiencies with autoimmunity.
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Submitted on : Tuesday, November 5, 2019 - 4:27:30 PM
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Caroline Besnard, Eva Levy, Nathalie Aladjidi, Marie-Claude Stolzenberg, Aude Magerus-Chatinet, et al.. Pediatric-onset Evans syndrome: Heterogeneous presentation and high frequency of monogenic disorders including LRBA and CTLA4 mutations. Clinical Immunology, Elsevier, 2018, 188, pp.52--57. ⟨10.1016/j.clim.2017.12.009⟩. ⟨hal-02349435⟩

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