Innate immunity defects in Hermansky-Pudlak type 2 syndrome.
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.
Fontana
Stefania
S
Istituto di Medicina Molecolare Angelo Nocivelli, Università di Brescia, c/o Spedali Civili, 25123 Brescia, Italy.
Parolini
Silvia
S
Vermi
William
W
Booth
Sarah
S
Gallo
Federico
F
Donini
Marta
M
Benassi
Marzia
M
Gentili
Francesca
F
Ferrari
Daniela
D
Notarangelo
Lucia D
LD
Cavadini
Patrizia
P
Marcenaro
Emanuela
E
Dusi
Stefano
S
Cassatella
Marco
M
Facchetti
Fabio
F
Griffiths
Gillian M
GM
Moretta
Alessandro
A
Notarangelo
Luigi D
LD
Badolato
Raffaele
R
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
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