Immunomodulation in an Infant with Familial Hemophagocytic Lymphohistiocytosis Following Chemotherapy

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 Tand NK-cell function; macrophage activation and cytokine production. Elevated transforming growth factor beta (TGF/3) 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/3, 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. TGF/3 (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 fiM) 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.'The

Hemophagocytic lymphohistiocytosis: A concise review for the practicing physician

“…The resulting hyperinflammatory state, characterized by fever, cytopenia, and hepatosplenomegaly, can be rapidly fatal if not recognized in time. 1 Furthermore, HLH can be the first manifestation of another primary immunodeficiency syndrome. 2 Therefore, even though HLH is a rare disease, the basic knowledge of its presentation and treatment is vital for not only practicing immunologists but also for hematologists and critical care physicians who may be involved in the care of these patients.…”