Immunomodulation in an Infant with Familial Hemophagocytic Lymphohistiocytosis Following Chemotherapy

Abstract

ABSTRACT

Familial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessive disorder associated with hepatosplenomegaly, cytopenias, lymphohistiocytic accumulation in the reticuloendothelial system and hemophagocytosis. Immunological dysregulation can occur with defective T-and NK-cell function; macrophage activation and cytokine production. Elevated transforming growth factor beta (TGF/β) produced by activated T cells and monocytes can be anti-inflammatory, whereas interleukin-6 (IL-6) induces T-cell proliferation and activation. We report the clinical and immunological evaluation of a 5-month-old Hispanic infant with FHLH. The evaluation included TGF/β, IL-6, nitric oxide (NO), and extended lymphocyte phenotypes, CD3+, CD4+, CD8+, CD28+, CD95+, CD45RA+, CD62L+, HLA-DR+, CD38+, CD69+ using enzyme-linked immunoadsorbent assay (ELISA), Greiss reagent, and 4′ color flow cytometry pre- and postchemotherapy with VP16 @ 65 mg/M² and dexamethasone over 10 courses of treatment. TGFβ (924.4–4286.8 pg/mL), IL-6 (215.4–4225 pg/mL) in PHA-stimulated supernatant mononuclear cells and serum NO (4.267–11.660 μM) dramatically increased post-treatment along with the percentage of CD8+ T cells (22–30%) and NK+ cells (2–14%). Resting naive cells (CD45RA+CD62L+) decreased in CD4+ (75–52%) and CD8+ (64–47%) subsets. T-cell activation was suggested by increases in CD95 expression on CD4+ cells (1–19%) and co-expression of CD38+CD69+ (1–23%) and HLA-DR+CD69+(l–25%) on CD8+ cells. Immunoregulatory cytokine changes along with T-cell and NK phenotypes may indicate a direct or indirect effect of chemotherapy on the pathogenesis of FHLH. Thus, a favorable clinical and immunological effect was noted following chemotherapy for FHLH.