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Immunohistochemical detection of ubiquitin‐positive intracytoplasmic eosinophilic inclusion bodies in diffuse alveolar damage
Author(s) -
Yamada T,
Uehara K,
Kawanishi R,
Mizutani T,
Sunagawa K,
Araya J,
Kawabata Y
Publication year - 2006
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2006.02445.x
Subject(s) - immunohistochemistry , pathology , eosinophilic , medicine , ubiquitin , biology , biochemistry , gene
Aims : To clarify the relationship between ubiquitin‐positive pneumocytes and intracytoplasmic eosinophilic inclusion bodies (IB) in patients who died of diffuse alveolar damage (DAD). Methods and results : Eighteen patients with DAD were studied, in whom hyaline membranes were present in one or more out of five sections from each lobe of the lungs and 15 patients with no DAD. Light microscopy revealed hyaline membrane in over 25% of lobes from 18 patients with DAD. The cytoplasm of pneumocytes from six of 18 cases of DAD contained IB. Immunohistochemically, all IBs were characteristically positive for both ubiquitin (Ub) and cytokeratin KL‐1. Cytoplasmic granules were also Ub+ in four cases of DAD without IB. IB+ or Ub+ pneumocytes were undetectable in non‐DAD patients. We evaluated DAD severity based on hyaline membrane formation; the mean score in DAD with IB (3.60; n = 6) was significantly higher than that in Ub– (2.92; n = 8). Ub+ pneumocytes were found with or without IB among those cases with high DAD scores. Conclusions : These findings suggest that disordered proteolysis in the Ub‐mediated proteasome system leads to the accumulation of abnormal ubiquitinated protein, which includes cytokeratin, in pneumocytes. This is the first report to suggest that Ub+ pneumocytes are associated with disease severity in patients with DAD.