@article{Vittorio Necchi_Antonella Minelli_Patrizia Sommi_Agostina Vitali_Roberta Caruso_Daniela Longoni_Maria Rita Frau_Cristina Nasi_Fabiola De Gregorio_Marco Zecca_Vittorio Ricci_Cesare Danesino_Enrico Solcia_2012, place={Pavia, Italy}, title={Ubiquitin-proteasome-rich cytoplasmic structures in neutrophils of patients with Shwachman-Diamond syndrome}, volume={97}, url={https://haematologica.org/article/view/6350}, DOI={10.3324/haematol.2011.048462}, abstractNote={<strong>Background</strong> Shwachman–Diamond syndrome is an autosomal recessive disorder in which severe bone marrow dysfunction causes neutropenia and an increased risk of leukemia. Recently, novel particulate cytoplasmic structures, rich in ubiquitinated and proteasomal proteins, have been detected in epithelial cells and neutrophils from patients with <em>Helicobacter pylori</em> gastritis and several epithelial neoplasms.<strong>Design and Methods</strong> Blood neutrophils from 13 cases of Shwachman–Diamond syndrome – ten with and three without <em>SBDS</em> gene mutation – and ten controls were investigated by confocal microscopy and ultrastructural immunocytochemistry using antibodies against ubiquitinated proteins, proteasomes, p62 protein, and <em>Helicobacter pylori</em> VacA, urease and outer membrane proteins.<strong>Results</strong> Many extensively disseminated particulate cytoplasmic structures, accounting for 22.78±5.57% (mean ± standard deviation) of the total cytoplasm, were found in blood neutrophils from mutated Shwachman–Diamond syndrome patients. The particulate cytoplasmic structures showed immunoreactivity for polyubiquitinated proteins and proteasomes, but no reactivity for <em>Helicobacter pylori</em> products, which are present in particulate cytoplasmic structures of <em>Helicobacter pylori</em>-positive gastritis. Neutrophils from patients with Shwachman–Diamond syndrome frequently showed p62-positive autophagic vacuoles and apoptotic changes in 5% of cells. No particulate cytoplasmic structures were observed in most control neutrophils; however, in a few cells from two cases we noted focal development of minute particulate cytoplasmic structures, accounting for 0.74±0.56% of the total cytoplasm (<em>P</em><0.001 <em>versus</em> particulate cytoplasmic structures from mutated Shwachman–Diamond syndrome patients). Neutrophils from non-mutated Shwachman–Diamond-syndrome-like patients resembled controls in two cases, and a third case showed particulate cytoplasmic structure patterns intermediate between those in controls and those in mutated Shwachman–Diamond syndrome patients.<strong>Conclusions</strong&gt; Particulate cytoplasmic structures are a prominent feature of neutrophils from patients with Shwachman–Diamond syndrome. They may help us to understand the mechanism of granulocyte dysfunction and the neoplastic risk of the disease.}, number={7}, journal={Haematologica}, author={Vittorio Necchi and Antonella Minelli and Patrizia Sommi and Agostina Vitali and Roberta Caruso and Daniela Longoni and Maria Rita Frau and Cristina Nasi and Fabiola De Gregorio and Marco Zecca and Vittorio Ricci and Cesare Danesino and Enrico Solcia}, year={2012}, month={Jul.}, pages={1057-1063} }