Pitfalls of immunotherapy: lessons from a patient with CTLA-4 haploinsufficiency.

摘要: Daclizumab is a humanized monoclonal antibody that blocks CD25, the high affinity alpha subunit of interleukin-2 receptor. therapy targets T regulatory cell and activated effector proliferation to suppress autoimmune disease activity, in inflammatory conditions like relapsing remitting multiple sclerosis. Here, we present first report agranulocytosis with daclizumab patient Our was 24-year-old Australian female clinical history atopy, lymphocytic enteritis complicated by B12 deficiency, sclerosis, recurrent lower respiratory tract infections, vulval/cervical intraepithelial neoplasia melanoma. She commenced on after failing several lines treatment for During hospital admission enteritis, she incidentally diagnosed combined immunodeficiency hypogammaglobulinaemia declined proposed regular intravenous immunoglobulin infusions. Following six months therapy, our presented febrile neutropenia. No clear infective cause found, despite numerous investigations. However, bone marrow biopsy revealed an apparent maturation block at myeloblasts stage. Neustrophil recovery occurred following cessation initiation immunosuppressive agents including systemic corticosteroids methotrexate. The further investigated whole exome sequencing novel heterozygous missense variant cytotoxic lymphocyte antigen 4 (CTLA4), leading diagnosis CTLA-4 haploinsufficiency infiltration (CHAI). This case demonstrates may be presenting feature primary should appropriately prior commencement immunotherapy. Genetic clarification underlying provide critical information alters safety strategy.