Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell–induced apoptosis

Abstract

In 65 patients with hemophagocytic lymphohistiocytosis (HLH), we found an as yet undescribed heterogeneity of defects in cellular cytotoxicity when assay conditions were modified by the incubation time, the presence of mitogen, or interleukin-2 (IL-2). The standard 4-hour natural killer (NK) test against K562 targets was negative in all patients. In patients deficient in type 1 (n ‫؍‬ 21), type 2 (n ‫؍‬ 5), and type 4 (n ‫؍‬ 8) HLH, negative NK function could be reconstituted by mitogen, by IL-2, or by prolongation of the incubation time (16 hours

Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis

“…Another laboratory test for HLH is NK cell activity, which is measured by the 51-Chromium release assay in which patient's NK cells that have taken up the radionuclide are stimulated to degranulate and lyse target cells. The NK cell activity is expected to be low or absent in HLH patients [30]. However, because of the technical challenges associated with performing this assay and the availability of the assay in a few of referral laboratories, NK cell activity has a limited utility in urgent clinical scenarios like HLH.…”

Patients with early relapse of primary hemophagocytic syndromes or with persistent CNS involvement may benefit from immediate hematopoietic stem cell transplantation

“…Marked hemophagocytosis is usually found in BM and other tissues such as spleen and liver, and infiltration of vital organs including the central nervous system (CNS) by activated CD8-positive T cells and by macrophages is a characteristic histomorphological finding. [4][5][6] A number of molecular defects have been detected in affected patients, although in a substantial proportion the underlying defect remains undefined. [7][8][9] Treatment by a combination of immunosuppressive agents, usually etoposide (VP-16) and intrathecal MTX as well as antithymocyte globulin (ATG) and CsA, usually leads to control of manifestations of accelerated phases and reinduction of remissions.…”

Mutations affecting mRNA splicing are the most common molecular defect in patients with familial hemophagocytic lymphohistiocytosis type 3

“…9,10 In particular, demonstration of frequent association with common pathogens, together with evidence of impaired natural killer cytotoxic activity, provided the rationale for considering HLH as a selective immune deficiency. [11][12][13] Starting from the original report by Farquhar et al in 1952, autosomal recessive inheritance was proposed as the basis for the familial form of HLH (FHLH or FHL).…”