Contemporary diagnostic methods for hemophagocytic lymphohistiocytic disorders

Hemophagocytic lymphohistiocytosis is a life-threatening multi-system hyperinflammatory disorder characterized by dysfunctional cytolytic lymphocyte responses, hypercytokinemia, and widespread lymphohistiocytic tissue infiltration and destruction. Diagnosis and definitive therapy are often delayed as clinical efforts are directed toward treatment of presumed overwhelming infection. Sporadic cases occur in association with underlying immune dysfunction related to autoimmune disease, malignancy, or severe infection. However, familial cases predominate with remarkable associations between underlying genetic defects and dysregulation of immune responses. Here, we review the genetic and immunologic basis of contemporary diagnostic methods for hemophagocytic lymphohistiocytosis.

Research Highlights► Genetic basis for hemophagocytic lymphohistiocytosis (HLH). ► Flow cytometric methods for HLH diagnosis. ► Assessment of T cell and NK cell effector function in HLH diagnosis. ► Useful biomarkers for following HLH disease progression.