Histone H1 is released from myonuclei and present in rimmed vacuoles with DNA in inclusion body myositis

To investigate myonuclear alterations in sporadic inclusion body myositis (s-IBM), we immuno-localized histones in muscles in 11 patients. The examination showed that vacuolar rims were frequently positive for histone H1. In triple-color fluorescence study, the H1-positive products were found on the inner side of an emerin-positive circle with DNA. Moreover, H1-positive materials appeared to be released into the cytoplasm in some vacuoles and myonuclei. The localization of H1 was different from phosphorylated Elk-1, which is a nuclear protein, but abnormally accumulated in the cytoplasm in s-IBM. The results strongly support the hypothesis that rimmed vacuoles are derived from the nucleus. The cytoplasmic H1-release suggests dysfunction of nuclear membranes in an early phase of the nuclear disintegration. We hypothesize that, in s-IBM muscles, compromised nuclear envelope may permit release of some nuclear components such as histone H1 and cannot facilitate the incorporation of others to the nucleus as in pElk-1.