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 _3A 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