JAK inhibition in a patient with a STAT1 gain-of-function variant reveals STAT1 dysregulation as a common feature of aplastic anemia.

ABSTRACT:

Background

Idiopathic aplastic anemia is a potentially lethal disease, characterized by T cell-mediated autoimmune attack of bone marrow hematopoietic stem cells. Standard of care therapies (stem cell transplantation or immunosuppression) are effective but associated with a risk of serious toxicities.

Methods

An 18-year-old man presented with aplastic anemia in the context of a germline gain-of-function variant in STAT1. Treatment with the JAK1 inhibitor itacitinib resulted in a rapid resolution of aplastic anemia and a sustained recovery of hematopoiesis. Peripheral blood and bone marrow samples were compared before and after JAK1 inhibitor therapy.

Findings

Following therapy, samples showed a decrease in the plasma concentration of interferon-γ, a decrease in PD1-po

SUBMITTER: Rosenberg JM 

PROVIDER: S-EPMC9123284 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature