PMC6196561_01
a Family pedigree: arrow indicates proband. Circles represent females, squares represent males; strikethrough represent deceased individuals, clinical conditions as outlined in key. b Flow cytometry of bone marrow aspirate demonstrating agranulocytosis with almost no cells in the granulocytic gate; lymphocytes are gated in green and blasts gated in blue. Bone marrow aspirate (c) and trephine (d) demonstrating a hypocellular marrow with adequate erythroid and megakaryocytic precursors but no maturing granulopoiesis. e Rapid resolution of tachycardia and fevers on commencement of systemic corticosteroids (green arrow). f Longitudinal neutrophil counts during course of admission with commencement of G-CSF (red arrow), corticosteroids (green arrow), oral methotrexate (blue arrow) and subcutaneous methotrexate (black arrow)
13223_2018_272_Fig1_HTML.jpg
PMC6196561_01_13223_2018_272_Fig1_HTML.jpg
Fig1
The family history was notable for combined variable immunodeficiency (CVID) in her brother and maternal aunt, both with autoimmune features, and her mother had alopecia (Fig. 1a; Tables 1, 2). Bone marrow biopsy revealed an agranulocytosis with an apparent maturation block at the myeloblasts stage but no features of hemophagocytosis and Epstein-Barr virus (EBV) in situ hybridization was negative (Fig. 1b-d). T cell immunosuppressive agents including systemic corticosteroids and methotrexate, the patient made a rapid recovery with resolution of fever and agranulocytosis within 3 weeks (Fig. 1e, f). The patient has not received any further daclizumab therapy and remains well on low dose prednisolone and methotrexate. T; p.Pro137Leu in exon 2 of CTLA4; Fig. 1a).