TY - JOUR
T1 - Occurrence of nodular lymphocyte-predominant Hodgkin lymphoma in Hermansky-Pudlak type 2 syndrome is associated to natural killer and natural killer T cell defects
AU - Lorenzi, Luisa
AU - Tabellini, Giovanna
AU - Vermi, William
AU - Moratto, Daniele
AU - Porta, Fulvio
AU - Notarangelo, Lucia D.
AU - Patrizi, Ornella
AU - Sozzani, Silvano
AU - Basile, Genevieve De Saint
AU - Latour, Sylvain
AU - Pace, David
AU - Lonardi, Silvia
AU - Facchetti, Fabio
AU - Badolato, Raffaele
AU - Parolini, Silvia
PY - 2013/11/26
Y1 - 2013/11/26
N2 - 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 CD56brightCD16- 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.
AB - 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 CD56brightCD16- 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.
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U2 - 10.1371/journal.pone.0080131
DO - 10.1371/journal.pone.0080131
M3 - Article
C2 - 24302998
AN - SCOPUS:84896721132
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 11
M1 - e80131
ER -