Evans syndrome caused by a deleterious mutation affecting the adaptor protein SASH3
Wolfgang Novak, Jakob Berner, Michael Svaton, Raul Jimenez‐Heredia, Anna Segarra‐Roca, Alexandra Frohne, Sarah Guiliani, David Rouhani, Sebastian K. Eder, Arno Rottal, Doris Trapin, Anja Scheuchenstuhl, Winfried F. Pickl, Ingrid Simonitsch‐Klupp, Leo Kager, Kaan Boztug - Hematology
Summary
Increasing evidence suggests multilineage cytopenias (also known as Evans syndrome) may be caused by inborn errors of immunity (IEI) with immune dysregulation. We studied a patient with autoimmune haemolytic anaemia and immune thrombocytopenia and identified a germline mutation in SASH3 (c.862C>T;p.Arg288Ter), indicating a recently identified IEI. Immunohistochemistry performed after clinically indicated splenectomy revealed severe hypoplasia/absence of germinal centres. The autoimmune phenotype was associated with an increased CD21lowT‐bet+CD11c+ subset along with decreased regulatory T cells, impaired T‐cell proliferation and T‐cell exhaustion. The younger brother carries the same SASH3 mutation and shares immunophenotypic features but is currently clinical asymptomatic, indicating heterogeneity of SASH3 deficiency.