title: Occurrence of nodular lymphocyte-predominant hodgkin lymphoma in hermansky-pudlak type 2 syndrome is associated to natural killer and natural killer T cell defects.
abstract: Hermansky Pudlak type 2 syndrome (HPS2) is a rare autosomal recessive primary immune deficiency caused by mutations on β3A gene (AP3B1 gene). The defect results in the impairment of the adaptor protein 3 (AP-3) complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL) in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf) + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56(bright)CD16(-) Natural Killer (NK) cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-γ production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients.
authors.affiliation: Department of Molecular and Translational Medicine, Section of Pathology, University of Brescia, Brescia, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Lorenzi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tabellini
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Daniele
authors.initials: D
authors.lastname: Moratto
authors.forename: Fulvio
authors.initials: F
authors.lastname: Porta
authors.forename: Lucia D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Ornella
authors.initials: O
authors.lastname: Patrizi
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.forename: Genevieve
authors.initials: G
authors.lastname: de Saint Basile
authors.forename: Sylvain
authors.initials: S
authors.lastname: Latour
authors.forename: David
authors.initials: D
authors.lastname: Pace
authors.forename: Silvia
authors.initials: S
authors.lastname: Lonardi
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
authors.forename: Silvia
authors.initials: S
authors.lastname: Parolini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D019002:CD56 Antigen / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D005260:Female; D022861:Hermanski-Pudlak Syndrome / Q000150:complications* / Q000175:diagnosis / Q000276:immunology*; D006689:Hodgkin Disease / Q000150:complications* / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D035781:Siblings; D060149:Tetraspanin 30 / Q000378:metabolism; D055815:Young Adult
chemical_list: D019002:CD56 Antigen; D052118:Lysosomal-Associated Membrane Protein 1; D060149:Tetraspanin 30; D007371:Interferon-gamma