Abstract 11093: Altered Natural Killer Cell Subsets, Phenotype and Activity in Adamts13-deficient TTP Patients With a History of Relapse
Thrombotic thrombocytopenic purpura (TTP) associated with deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) is a vascular disease with thrombotic microangiopathy characterized by acute episodes of widespread microvascular thrombosis. Approximately 40% of patients with this autoimmune disorder are susceptible to relapses, but mechanisms governing this predilection are unknown. Natural killer (NK) cells are important regulators of the immune system. To determine whether NK cells may play a role in TTP relapse, we characterized their frequency, phenotype and activity in 11 ADAMTS13-deficient TTP patients with a history of relapse and 18 patients who had only suffered a single episode. All samples were collected during disease remission. CD56dim NK cells play a major role in cytotoxicity, while CD56bright NK cells are thought to have regulatory activity. Flow cytometry of live PBMC recovered from frozen samples showed that frequencies of CD56brightCD16- NK cells are increased in TTP patients with a history of relapse, while frequencies of CD56dimCD16- NK cells are downregulated in patients with a history of relapse. Production of granzyme A and IFN-γ by CD3-CD56dim NK cells following in vitro stimulation with PMA and ionomycin was increased in the relapse group. Finally, measurement of cell surface markers without in vitro stimulation showed significantly increased expression levels of HLA-DR and CD69 on the surface of CD56dimCD16+ NK cells, suggesting prior activation of this subset in vivo. Surface levels of CD52 were elevated on CD16- NK cell subsets and CD56dimCD16+ NK cells but were selectively reduced on the CD56brightCD16+ subset in patients with a history of relapse compared to the non-relapsing group. These data provide evidence of altered NK cell activation and/or licensing in TTP patients with a history of relapse and constitute a new avenue of investigation into mechanisms of TTP immunopathogenesis.
- © 2013 by American Heart Association, Inc.