title: Innate immunity defects in Hermansky-Pudlak type 2 syndrome.
abstract: Adaptor protein-3 (AP-3) is an ubiquitous cytoplasmic complex that shuttles cargo proteins from the trans-Golgi and a tubular-endosomal compartment to endosome-lysosome-related organelles. Lack of the beta3A subunit of this complex causes Hermansky-Pudlak syndrome type 2, an autosomal recessive disease characterized by partial albinism, prolonged bleeding tendency, and immunodeficiency. To investigate the pathogenesis of immunodeficiency, we studied natural killer (NK) cells and neutrophil functions in 2 previously unreported siblings affected by Hermansky-Pudlak type 2 syndrome. In both patients we observed a dramatic reduction of cytolytic activity of freshly isolated and of IL-2-activated NK cells. Levels of perforin were reduced in unstimulated NK cells, thereby accounting for the impairment of NK cytolitic activity. In addition, analysis of neutrophils in these patients demonstrated that intracellular elastase content was largely reduced while CD63 expression on plasma membrane was substantially increased. Taken together, these observations suggest that type 2 Hermansky-Pudlak syndrome is characterized by defects of innate immunity.
authors.affiliation: Istituto di Medicina Molecolare Angelo Nocivelli, Università di Brescia, c/o Spedali Civili, 25123 Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Fontana
authors.forename: Silvia
authors.initials: S
authors.lastname: Parolini
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Sarah
authors.initials: S
authors.lastname: Booth
authors.forename: Federico
authors.initials: F
authors.lastname: Gallo
authors.forename: Marta
authors.initials: M
authors.lastname: Donini
authors.forename: Marzia
authors.initials: M
authors.lastname: Benassi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gentili
authors.forename: Daniela
authors.initials: D
authors.lastname: Ferrari
authors.forename: Lucia D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cavadini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
authors.forename: Stefano
authors.initials: S
authors.lastname: Dusi
authors.forename: Marco
authors.initials: M
authors.lastname: Cassatella
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Griffiths
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000276:immunology*; D033966:Adaptor Protein Complex beta Subunits / Q000276:immunology*; D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D022861:Hermanski-Pudlak Syndrome / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000473:pathology; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D019272:Leukocyte Elastase / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D010980:Platelet Membrane Glycoproteins / Q000276:immunology*; D060149:Tetraspanin 30; D021601:trans-Golgi Network / Q000276:immunology
chemical_list: C439973:AP3B1 protein, human; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D015703:Antigens, CD; C554586:CD63 protein, human; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D019272:Leukocyte Elastase