title: Development of hemophagocytic lymphohistiocytosis in triplets infected with HHV-8.
abstract: Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of immune dysregulation, characterized by end-organ damage from lymphocytic infiltration and macrophage activation. All known mutations associated with the HLH occur in genes critical in the perforin-granzyme pathway. Herein, we report HLH occurring in 2 female triplet infants who also had associated human herpesvirus type 8 (HHV-8) infections. The subjects had identical novel compound-heterozygous mutations in the Perforin alleles, resulting in undetectable perforin expression and NK-cell cytotoxicity. Both infants also had evidence of infection with HHV-8. These reports are, to our knowledge, the first cases of HLH in triplets and the first reported cases of HHV-8 infection associated with HLH in non-renal transplant and non-HIV-infected subjects.
authors.affiliation: Division of Pediatric Hematology, Oncology, Blood, and Marrow Transplant, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Grossman
authors.forename: Mohammed
authors.initials: M
authors.lastname: Radhi
authors.forename: Dennis
authors.initials: D
authors.lastname: Schauer
authors.forename: Erick
authors.initials: E
authors.lastname: Gerday
authors.forename: Charles
authors.initials: C
authors.lastname: Grose
authors.forename: Frederick D
authors.initials: FD
authors.lastname: Goldman
mesh_terms: D005260:Female; D006566:Herpesviridae Infections / Q000209:etiology*; D019288:Herpesvirus 8, Human; D006579:Heterozygote; D015616:Histiocytosis, Non-Langerhans-Cell / Q000235:genetics* / Q000821:virology*; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural; D008562:Membrane Glycoproteins / Q000235:genetics; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic; D014310:Triplets / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin